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Sample records for degradation erad pathway

  1. A vacuolar carboxypeptidase mutant of Arabidopsis thaliana is degraded by the ERAD pathway independently of its N-glycan

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    Yamamoto, Masaya; Kawanabe, Mitsuyoshi; Hayashi, Yoko; Endo, Toshiya [Department of Chemistry, Graduate School of Science, Nagoya University, Chikusa-ku, Nagoya 464-8602 (Japan); Nishikawa, Shuh-ichi, E-mail: shuh@biochem.chem.nagoya-u.ac.jp [Department of Chemistry, Graduate School of Science, Nagoya University, Chikusa-ku, Nagoya 464-8602 (Japan)

    2010-03-12

    Misfolded proteins produced in the endoplasmic reticulum (ER) are degraded by a mechanism, the ER-associated degradation (ERAD). Here we report establishment of the experimental system to analyze the ERAD in plant cells. Carboxypeptidase Y (CPY) is a vacuolar enzyme and its mutant CPY* is degraded by the ERAD in yeast. Since Arabidopsis thaliana has AtCPY, an ortholog of yeast CPY, we constructed and expressed fusion proteins consisting of AtCPY and GFP and of AtCPY*, which carries a mutation homologous to yeast CPY*, and GFP in A. thaliana cells. While AtCPY-GFP was efficiently transported to the vacuole, AtCPY*-GFP was retained in the ER to be degraded in proteasome- and Cdc48-dependent manners. We also found that AtCPY*-GFP was degraded by the ERAD in yeast cells, but that its single N-glycan did not function as a degradation signal in yeast or plant cells. Therefore, AtCPY*-GFP can be used as a marker protein to analyze the ERAD pathway, likely for nonglycosylated substrates, in plant cells.

  2. Gamma radiolytic eradication of methoxychlor in aqueous media. The degradation pathways using HPLC and SPME-GC-MS

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    Butt, S.B.; Zafar, A. [PINSTECH, Nilore, Islamabad (Pakistan). Central Analytical Facility Div.; Riaz, M. [PINSTECH, Nilore, Islamabad (Pakistan). Chemistry Div.

    2013-08-01

    The gamma radiation-induced degradation of environmental pollutant methoxychlor in water was investigated. A {sup 60}Co gamma radiation source with a dose rate of 372 Gy h{sup -1} was used for gamma irradiation of 1 mg L{sup -1} and 10 mg L{sup -1} methoxychlor in water with a varied absorbed dose of 1-5 kGy. A single step clean up and pre-concentration procedure based on solid phase micro-extraction was optimized. The extent of radiolytic degradation was monitored by reversed phase HPLC-UV and GC-ECD. The trace and ultra trace level degradation products were identified using GC-MS-SPME by comparing their mass spectra with the NIST 98 m mass spectral library. Most of the generated products for 4 kGy dose are substituted chlorophenols. The reaction pathways of these substituted chlorophenols and benzophenone formation are also proposed. However, generated chlorophenols disappeared along with methoxychlor for an absorbed dose of 5 kGy. The attained degradation of methoxychlor is {proportional_to} 95% that reflects the potential use of ionization radiation for wastewater treatment. (orig.)

  3. RNF185 is a novel E3 ligase of endoplasmic reticulum-associated degradation (ERAD) that targets cystic fibrosis transmembrane conductance regulator (CFTR).

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    El Khouri, Elma; Le Pavec, Gwenaëlle; Toledano, Michel B; Delaunay-Moisan, Agnès

    2013-10-25

    In the endoplasmic reticulum (ER), misfolded or improperly assembled proteins are exported to the cytoplasm and degraded by the ubiquitin-proteasome pathway through a process called ER-associated degradation (ERAD). ER-associated E3 ligases, which coordinate substrate recognition, export, and proteasome targeting, are key components of ERAD. Cystic fibrosis transmembrane conductance regulator (CFTR) is one ERAD substrate targeted to co-translational degradation by the E3 ligase RNF5/RMA1. RNF185 is a RING domain-containing polypeptide homologous to RNF5. We show that RNF185 controls the stability of CFTR and of the CFTRΔF508 mutant in a RING- and proteasome-dependent manner but does not control that of other classical ERAD model substrates. Reciprocally, its silencing stabilizes CFTR proteins. Turnover analyses indicate that, as RNF5, RNF185 targets CFTR to co-translational degradation. Importantly, however, simultaneous depletion of RNF5 and RNF185 profoundly blocks CFTRΔF508 degradation not only during translation but also after synthesis is complete. Our data thus identify RNF185 and RNF5 as a novel E3 ligase module that is central to the control of CFTR degradation.

  4. TMEM129 is a Derlin-1 associated ERAD E3 ligase essential for virus-induced degradation of MHC-I

    DEFF Research Database (Denmark)

    van den Boomen, Dick J H; Timms, Richard T; Grice, Guinevere L

    2014-01-01

    role for ubiquitin in this degradation pathway, the responsible E3 ligase is unknown. In a forward genetic screen for host ERAD components hijacked by US11 in near-haploid KBM7 cells, we identified TMEM129, an uncharacterized polytopic membrane protein. TMEM129 is essential and rate-limiting for US11......-mediated MHC-I degradation and acts as a novel ER resident E3 ubiquitin ligase. TMEM129 contains an unusual cysteine-only RING with intrinsic E3 ligase activity and is recruited to US11 via Derlin-1. Together with its E2 conjugase Ube2J2, TMEM129 is responsible for the ubiquitination, dislocation......, and subsequent degradation of US11-associated MHC-I. US11 engages two degradation pathways: a Derlin-1/TMEM129-dependent pathway required for MHC-I degradation and a SEL1L/HRD1-dependent pathway required for "free" US11 degradation. Our data show that TMEM129 is a novel ERAD E3 ligase and the central component...

  5. Protein Kinase C: One Pathway towards the Eradication of Latent HIV-1 Reservoirs

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    Lisa N. McKernan

    2012-01-01

    Full Text Available An effective means to eradicate latent reservoirs in HIV-1-infected individuals remains elusive. Attempts to purge these reservoirs were undertaken over a decade ago without success. The subsequent lapse in further clinical attempts since may have been justified as our knowledge of the mechanisms which underpin the latent state still evolves. Although additional novel molecular antagonists of HIV-1 latency have subsequently been reported, these candidate agents have not been tested in human trials for reservoir ablation. This review provides an overview of the protein kinase C (PKC pathway which can be modulated by small molecular agents to induce the expression of latent HIV-1 from within infected reservoir cells. Some of these agents have been tested against select cancers with seemingly tolerable side effects. As such, modulation of the PKC pathway may yet be a viable mechanism toward HIV-1 reservoir eradication.

  6. Pro-inflammatory cytokines enhance ERAD and ATF6α pathway activity in salivary glands of Sjögren's syndrome patients.

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    Barrera, María-José; Aguilera, Sergio; Castro, Isabel; Cortés, Juan; Bahamondes, Verónica; Quest, Andrew F G; Molina, Claudio; González, Sergio; Hermoso, Marcela; Urzúa, Ulises; Leyton, Cecilia; González, María-Julieta

    2016-12-01

    Salivary gland (SG) acinar-cells are susceptible to endoplasmic reticulum (ER) stress related to their secretory activity and the complexity of synthesized secretory products. SGs of Sjögren's syndrome patients (SS)-patients show signs of inflammation and altered proteostasis, associated with low IRE1α/XBP-1 pathway activity without avert increases in apoptosis. Acinar-cells may avoid apoptosis by activation of the ATF6α pathway and ER-associated protein degradation (ERAD). The aim of this study was to evaluate the role of pro-inflammatory cytokines in ATF6α pathway/ERAD activation and cell viability in labial salivary glands (LSG) of SS-patients. In biopsies from SS-patients increased ATF6α signaling pathway activity, as evidenced by generation of the ATF6f cleavage fragment, and increased expression of ERAD machinery components, such as EDEM1, p97, SEL1L, gp78, UBE2J1, UBE2G2, HERP and DERLIN1, were observed compared to controls. Alternatively, for pro- (active-caspase-3) and anti-apoptotic (cIAP2) markers no significant difference between the two experimental groups was detected. Increased presence of ATF6f and ERAD molecules correlated significantly with increased expression of pro-inflammatory cytokines. These observations were corroborated in vitro in 3D-acini treated with TNF-α and/or IFN-γ, where an increase in the expression and activation of the ATF6α sensor and ERAD machinery components was detected under ER stress conditions, while changes in cell viability and caspase-3 activation were not observed. Cytokine stimulation protected cells from death when co-incubated with an ERAD machinery inhibitor. Alternatively, when cytokines were eliminated from the medium prior to ERAD inhibition, cell death increased, suggesting that the presence of pro-inflammatory cytokines in the medium is essential to maintain cell viability. In conclusion, the ATF6α pathway and the ERAD machinery are active in LSG of SS-patients. Both were also activated by TNF

  7. Turnover of C99 is Controlled by a Crosstalk between ERAD and Ubiquitin-Independent Lysosomal Degradation in Human Neuroglioma Cells

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    Bustamante, Hianara A.; Rivera-Dictter, Andrés; Cavieres, Viviana A.; Muñoz, Vanessa C.; González, Alexis; Lin, Yimo; Mardones, Gonzalo A.; Burgos, Patricia V.

    2013-01-01

    Alzheimer’s disease (AD) is characterized by the buildup of amyloid-β peptides (Aβ) aggregates derived from proteolytic processing of the β-amyloid precursor protein (APP). Amyloidogenic cleavage of APP by β-secretase/BACE1 generates the C-terminal fragment C99/CTFβ that can be subsequently cleaved by γ-secretase to produce Aβ. Growing evidence indicates that high levels of C99/CTFβ are determinant for AD. Although it has been postulated that γ-secretase-independent pathways must control C99/CTFβ levels, the contribution of organelles with degradative functions, such as the endoplasmic reticulum (ER) or lysosomes, is unclear. In this report, we investigated the turnover and amyloidogenic processing of C99/CTFβ in human H4 neuroglioma cells, and found that C99/CTFβ is localized at the Golgi apparatus in contrast to APP, which is mostly found in endosomes. Conditions that localized C99/CTFβ to the ER resulted in its degradation in a proteasome-dependent manner that first required polyubiquitination, consistent with an active role of the ER associated degradation (ERAD) in this process. Furthermore, when proteasomal activity was inhibited C99/CTFβ was degraded in a chloroquine (CQ)-sensitive compartment, implicating lysosomes as alternative sites for its degradation. Our results highlight a crosstalk between degradation pathways within the ER and lysosomes to avoid protein accumulation and toxicity. PMID:24376644

  8. RNAi screening for characterisation of ER-associated degradation pathways in mammalian cells

    DEFF Research Database (Denmark)

    Månsson, Mats David Joakim

    It is estimated that one third of all synthesized proteins in mammalian cells traverse the secretory pathway. Folding of proteins in the ER on their way to secretion is highly regulated. Proteins that are unable to achieve their native conformation are degraded by the ubiquitin-proteasome system...... fluorescence-based RNAi screens in mammalian cells on TCR-α-GFP and HANSκLC, for identification of ERAD pathways. By validating the obtained screening hits we concluded that UBE2J2 is involved in TCR-α-GFP degradation, possibly by ubiquitination of C-terminal serine residues in TCR-α-GFP. Additionally, we also...

  9. Microbial PAH-Degradation in Soil: Degradation Pathways and Contributing Factors

    Institute of Scientific and Technical Information of China (English)

    ZHANG Xu-Xiang; CHENG Shu-Pei; ZHU Cheng-Jun; SUN Shi-Lei

    2006-01-01

    Adverse effects on the environment and high persistence in the microbial degradation and environmental fate of polycyclic aromatic hydrocarbons (PAHs) are motivating interest. Many soil microorganisms can degrade PAHs and use various metabolic pathways to do so. However, both the physio-chemical characteristics of compounds as well as the physical, chemical, and biological properties of soils can drastically influence the degradation capacity of naturally occurring microorganisms for field bioremediation. Modern biological techniques have been widely used to promote the efficiency of microbial PAH-degradation and make the biodegradation metabolic pathways more clear. In this review microbial degradation of PAHs in soil is discussed, with emphasis placed on the main degradation pathways and the environmental factors affecting biodegradation.

  10. Inhibitors and pathways of hepatocytic protein degradation.

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    Seglen, P O; Gordon, P B; Grinde, B; Solheim, A; Kovács, A L; Poli, A

    1981-01-01

    On the basis of experiments using amino acids and various inhibitors (lysosomotropic amines, leupeptin, chymostatin, vanadate, vinblastine, anoxia, methylaminopurines), five different modes of endogenous protein degradation in isolated rat hepatocytes can be distinguished. The two non-lysosomal (amine-resistant) mechanisms preferentially degrade relatively labile (short-lived) proteins: one of these mechanisms is energy-dependent and chymostatin-sensitive, the other is not. Of the three lysosomal (amine-sensitive) mechanisms, one--quantitatively minor--is amino acid-resistant and preferentially degrades labile proteins. The two amino acid-sensitive mechanisms each seen account for about one-half of the degradation of relatively stable (long-lived) proteins; one of them is suppressed by leucine and apparently corresponds to the formation of electron microscopically visible autophagosomes; the other may represent a different type of autophagy, inhibited by asparagine and glutamine. A new class of inhibitors, the purine derivatives (methylated 6-aminopurines, and 6-mercaptopurines) appear to specifically suppress autophagic/lysosomal protein degradation, and may help to further elucidate the mechanisms of autophagy.

  11. Sterol homeostasis requires regulated degradation of squalene monooxygenase by the ubiquitin ligase Doa10/Teb4

    DEFF Research Database (Denmark)

    Foresti, Ombretta; Ruggiano, Annamaria; Hannibal-Bach, Hans K

    2013-01-01

    ligase implicated in a branch of the endoplasmic reticulum (ER)-associated protein degradation (ERAD) pathway. Since the other branch of ERAD is required for HMGR regulation, our results reveal a fundamental role for ERAD in sterol homeostasis, with the two branches of this pathway acting together...

  12. Cytolethal distending toxins require components of the ER-associated degradation pathway for host cell entry.

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    Aria Eshraghi

    2014-07-01

    Full Text Available Intracellular acting protein exotoxins produced by bacteria and plants are important molecular determinants that drive numerous human diseases. A subset of these toxins, the cytolethal distending toxins (CDTs, are encoded by several Gram-negative pathogens and have been proposed to enhance virulence by allowing evasion of the immune system. CDTs are trafficked in a retrograde manner from the cell surface through the Golgi apparatus and into the endoplasmic reticulum (ER before ultimately reaching the host cell nucleus. However, the mechanism by which CDTs exit the ER is not known. Here we show that three central components of the host ER associated degradation (ERAD machinery, Derlin-2 (Derl2, the E3 ubiquitin-protein ligase Hrd1, and the AAA ATPase p97, are required for intoxication by some CDTs. Complementation of Derl2-deficient cells with Derl2:Derl1 chimeras identified two previously uncharacterized functional domains in Derl2, the N-terminal 88 amino acids and the second ER-luminal loop, as required for intoxication by the CDT encoded by Haemophilus ducreyi (Hd-CDT. In contrast, two motifs required for Derlin-dependent retrotranslocation of ERAD substrates, a conserved WR motif and an SHP box that mediates interaction with the AAA ATPase p97, were found to be dispensable for Hd-CDT intoxication. Interestingly, this previously undescribed mechanism is shared with the plant toxin ricin. These data reveal a requirement for multiple components of the ERAD pathway for CDT intoxication and provide insight into a Derl2-dependent pathway exploited by retrograde trafficking toxins.

  13. Cytolethal distending toxins require components of the ER-associated degradation pathway for host cell entry.

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    Eshraghi, Aria; Dixon, Shandee D; Tamilselvam, Batcha; Kim, Emily Jin-Kyung; Gargi, Amandeep; Kulik, Julia C; Damoiseaux, Robert; Blanke, Steven R; Bradley, Kenneth A

    2014-07-01

    Intracellular acting protein exotoxins produced by bacteria and plants are important molecular determinants that drive numerous human diseases. A subset of these toxins, the cytolethal distending toxins (CDTs), are encoded by several Gram-negative pathogens and have been proposed to enhance virulence by allowing evasion of the immune system. CDTs are trafficked in a retrograde manner from the cell surface through the Golgi apparatus and into the endoplasmic reticulum (ER) before ultimately reaching the host cell nucleus. However, the mechanism by which CDTs exit the ER is not known. Here we show that three central components of the host ER associated degradation (ERAD) machinery, Derlin-2 (Derl2), the E3 ubiquitin-protein ligase Hrd1, and the AAA ATPase p97, are required for intoxication by some CDTs. Complementation of Derl2-deficient cells with Derl2:Derl1 chimeras identified two previously uncharacterized functional domains in Derl2, the N-terminal 88 amino acids and the second ER-luminal loop, as required for intoxication by the CDT encoded by Haemophilus ducreyi (Hd-CDT). In contrast, two motifs required for Derlin-dependent retrotranslocation of ERAD substrates, a conserved WR motif and an SHP box that mediates interaction with the AAA ATPase p97, were found to be dispensable for Hd-CDT intoxication. Interestingly, this previously undescribed mechanism is shared with the plant toxin ricin. These data reveal a requirement for multiple components of the ERAD pathway for CDT intoxication and provide insight into a Derl2-dependent pathway exploited by retrograde trafficking toxins.

  14. Phenanthrene-degrading pathway of Agrobacterium sp. Phx1

    Institute of Scientific and Technical Information of China (English)

    ZHANG; Lei; YUAN; Hongli; WANG; Shuangqing; HUANG; Huaize

    2005-01-01

    The metabolic pathway of phenanthrene-degrading strain Agrobacterium sp. Phx1 was investigated. Phx1 almost was able to transform 100 υg/mL of phenanthrene completely in 1 day in broth media of beef extract-peptone (BP), Luria-Bertani (LB) and mineral salts media (MS), and LB and BP could promote the growth and degradation efficiency of Phx1. The GC-MS was employed to analyze the metabolites of the 1st, 3rd, 7th days of phenanthrene degradation in MS. As a result, the 1-Hydroxy-2-naphthoic acid (1H2N) and 1-naphthol (NOL) were detected in the metabolites of the 1st day. Only NOL was observed on the 3rd day and it disappeared on the 7th day. The accumulated NOL did not pertain to the defined pathway of phenanthrene degradation by bacteria. The further HPLC study confirmed the finding in GC-MS analysis and found the production of catechol (CAT) from o-phthalic acid (OPA) in the phenanthrene metabolizing, which has never been reported in the defined degrading pathways. This production was also evidenced by the production of CAT using OPA as substrate. All of our results showed that the Agrobacterium sp. Phx1 had a novel phenanthrene-degrading pathway.

  15. When RNA and protein degradation pathways meet

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    Pascal eGENSCHIK

    2014-04-01

    Full Text Available RNA silencing has become a major focus of molecular and biomedical research in the last decade. This mechanism, which is conserved in most eukaryotes, has been extensively studied and is associated to various pathways implicated in the regulation of development, in the control of transposition events, heterochromatin maintenance and also playing a role in defense against viruses. Despite of its importance, the regulation of the RNA silencing machinery itself remains still poorly explored. Recently several reports in both plants and metazoans revealed that key components of RNA silencing, such as RNA-induced silencing complex (RISC component ARGONAUTE proteins, but also the endonuclease Dicer are subjected to proteasomal and autophagic pathways. Here we will review these post-translational proteolytic regulations with a special emphasis on plant research and also discuss their functional relevance.

  16. Cathodic degradation of antibiotics: characterization and pathway analysis.

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    Kong, Deyong; Liang, Bin; Yun, Hui; Cheng, Haoyi; Ma, Jincai; Cui, Minhua; Wang, Aijie; Ren, Nanqi

    2015-04-01

    Antibiotics in wastewaters must be degraded to eliminate their antibacterial activity before discharging into the environment. A cathode can provide continuous electrons for the degradation of refractory pollutants, however the cathodic degradation feasibility, efficiency and pathway for different kinds of antibiotics is poorly understood. Here, we investigated the degradation of four antibiotics, namely nitrofurazone (NFZ), metronidazole (MNZ), chloramphenicol (CAP), and florfenicol (FLO) by a poised cathode in a dual chamber electrochemical reactor. The cyclic voltammetry preliminarily proved the feasibility of the cathodic degradation of these antibiotics. The cathodic reducibility of these antibiotics followed the order of NFZ > MNZ > CAP > FLO. A decreased phosphate buffered solution (PBS) concentration as low as 2 mM or utilization of NaCl buffer solution as catholyte had significant influence on antibiotics degradation rate and efficiency for CAP and FLO but not for NFZ and MNZ. PBS could be replaced by Na2CO3-NaHCO3 buffer solution as catholyte for the degradation of these antibiotics. Reductive dechlorination of CAP proceeded only after the reduction of the nitro group to aromatic amine. The composition of the degradation products depended on the cathode potential except for MNZ. The cathodic degradation process could eliminate the antibacterial activity of these antibiotics. The current study suggests that the electrochemical reduction could serve as a potential pretreatment or advanced treatment unit for the treatment of antibiotics containing wastewaters. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Epoxy Coenzyme A Thioester pathways for degradation of aromatic compounds.

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    Ismail, Wael; Gescher, Johannes

    2012-08-01

    Aromatic compounds (biogenic and anthropogenic) are abundant in the biosphere. Some of them are well-known environmental pollutants. Although the aromatic nucleus is relatively recalcitrant, microorganisms have developed various catabolic routes that enable complete biodegradation of aromatic compounds. The adopted degradation pathways depend on the availability of oxygen. Under oxic conditions, microorganisms utilize oxygen as a cosubstrate to activate and cleave the aromatic ring. In contrast, under anoxic conditions, the aromatic compounds are transformed to coenzyme A (CoA) thioesters followed by energy-consuming reduction of the ring. Eventually, the dearomatized ring is opened via a hydrolytic mechanism. Recently, novel catabolic pathways for the aerobic degradation of aromatic compounds were elucidated that differ significantly from the established catabolic routes. The new pathways were investigated in detail for the aerobic bacterial degradation of benzoate and phenylacetate. In both cases, the pathway is initiated by transforming the substrate to a CoA thioester and all the intermediates are bound by CoA. The subsequent reactions involve epoxidation of the aromatic ring followed by hydrolytic ring cleavage. Here we discuss the novel pathways, with a particular focus on their unique features and occurrence as well as ecological significance.

  18. Disulfiram Eradicates Tumor-Initiating Hepatocellular Carcinoma Cells in ROS-p38 MAPK Pathway-Dependent and -Independent Manners

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    Yuki, Kaori; Zen, Yoh; Oshima, Motohiko; Miyagi, Satoru; Saraya, Atsunori; Koide, Shuhei; Motoyama, Tenyu; Ogasawara, Sadahisa; Ooka, Yoshihiko; Tawada, Akinobu; Nakatsura, Tetsuya; Hayashi, Takehiro; Yamashita, Taro; Kaneko, Syuichi; Miyazaki, Masaru; Iwama, Atsushi; Yokosuka, Osamu

    2014-01-01

    Tumor-initiating cells (TICs) play a central role in tumor development, metastasis, and recurrence. In the present study, we investigated the effect of disulfiram (DSF), an inhibitor of aldehyde dehydrogenase, toward tumor-initiating hepatocellular carcinoma (HCC) cells. DSF treatment suppressed the anchorage-independent sphere formation of both HCC cells. Flow cytometric analyses showed that DSF but not 5-fluorouracil (5-FU) drastically reduces the number of tumor-initiating HCC cells. The sphere formation assays of epithelial cell adhesion molecule (EpCAM)+ HCC cells co-treated with p38-specific inhibitor revealed that DSF suppresses self-renewal capability mainly through the activation of reactive oxygen species (ROS)-p38 MAPK pathway. Microarray experiments also revealed the enrichment of the gene set involved in p38 MAPK signaling in EpCAM+ cells treated with DSF but not 5-FU. In addition, DSF appeared to downregulate Glypican 3 (GPC3) in a manner independent of ROS-p38 MAPK pathway. GPC3 was co-expressed with EpCAM in HCC cell lines and primary HCC cells and GPC3-knockdown reduced the number of EpCAM+ cells by compromising their self-renewal capability and inducing the apoptosis. These results indicate that DSF impaired the tumorigenicity of tumor-initiating HCC cells through activation of ROS-p38 pathway and in part through the downregulation of GPC3. DSF might be a promising therapeutic agent for the eradication of tumor-initiating HCC cells. PMID:24454751

  19. Disulfiram eradicates tumor-initiating hepatocellular carcinoma cells in ROS-p38 MAPK pathway-dependent and -independent manners.

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    Tetsuhiro Chiba

    Full Text Available Tumor-initiating cells (TICs play a central role in tumor development, metastasis, and recurrence. In the present study, we investigated the effect of disulfiram (DSF, an inhibitor of aldehyde dehydrogenase, toward tumor-initiating hepatocellular carcinoma (HCC cells. DSF treatment suppressed the anchorage-independent sphere formation of both HCC cells. Flow cytometric analyses showed that DSF but not 5-fluorouracil (5-FU drastically reduces the number of tumor-initiating HCC cells. The sphere formation assays of epithelial cell adhesion molecule (EpCAM(+ HCC cells co-treated with p38-specific inhibitor revealed that DSF suppresses self-renewal capability mainly through the activation of reactive oxygen species (ROS-p38 MAPK pathway. Microarray experiments also revealed the enrichment of the gene set involved in p38 MAPK signaling in EpCAM(+ cells treated with DSF but not 5-FU. In addition, DSF appeared to downregulate Glypican 3 (GPC3 in a manner independent of ROS-p38 MAPK pathway. GPC3 was co-expressed with EpCAM in HCC cell lines and primary HCC cells and GPC3-knockdown reduced the number of EpCAM(+ cells by compromising their self-renewal capability and inducing the apoptosis. These results indicate that DSF impaired the tumorigenicity of tumor-initiating HCC cells through activation of ROS-p38 pathway and in part through the downregulation of GPC3. DSF might be a promising therapeutic agent for the eradication of tumor-initiating HCC cells.

  20. Degradation of aromatic compounds and degradative pathway of 4-nitrocatechol by Ochrobactrum sp. B2.

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    Zhong, Qiuzan; Zhang, Haiyan; Bai, Wenqin; Li, Mei; Li, Baotong; Qiu, Xinghui

    2007-12-01

    The potential capacity of a soil methyl parathion-degrading bacterium strain, Ochrobactrum sp. B2, for degrading various aromatic compounds were investigated. The results showed B2 was capable of degrading diverse aromatic compounds, but amino-substituted benzene compounds, at a concentration up to 100 mg L(-1) in 4 days. B2 could use 4-nitrocatechol (4-NC) as a sole carbon and energy source with release of nitrite ion. The pathway for 4-NC degradation via 1,2,4-benzenetriol (BT) and hydroquinone (HQ) formation in B2 was proposed based on the identification and quantification of intermediates by gas chromatography-mass spectrometry (GC-MS), and high performance liquid chromatography (HPLC). Degradation studies carried out on a plasmid-cured derivative showed that the genes for 4-NC degradative pathway was plasmid-borne in B2, suggesting that B2 degrades both p-nitrophenol and 4-NC by enzymes encoded by genes on the same plasmid.

  1. Vacuole import and degradation pathway:Insights into a specialized autophagy pathway

    Institute of Scientific and Technical Information of China (English)

    Abbas; A; Alibhoy; Hui-Ling; Chiang

    2011-01-01

    Glucose deprivation induces the synthesis of pivotagluconeogenic enzymes such as fructose-1,6-bisphos-phatase, malate dehydrogenase, phosphoenolpyruvatecarboxykinase and isocitrate lyase in Saccharomycescerevisiae. However, following glucose replenishment,these gluconeogenic enzymes are inactivated and de-graded. Studies have characterized the mechanismsby which these enzymes are inactivated in response toglucose. The site of degradation of these proteins hasalso been ascertained to be dependent on the dura-tion of starvation. Glucose replenishment of short-termstarved cells results in these proteins being degradedin the proteasome. In contrast, addition of glucose tocells starved for a prolonged period results in theseproteins being degraded in the vacuole. In the vacuoledependent pathway, these proteins are sequestered inspecialized vesicles termed vacuole import and degra-dation (Vid). These vesicles converge with the endo-cytic pathway and deliver their cargo to the vacuolefor degradation. Recent studies have identified thatinternalization, as mediated by actin polymerization, isessential for delivery of cargo proteins to the vacuolefor degradation. In addition, components of the targetof rapamycin complex 1 interact with cargo proteins during glucose starvation. Furthermore, Tor1p dissoci-ates from cargo proteins following glucose replenish-ment. Future studies will be needed to elaborate on the importance of internalization at the plasma membrane and the subsequent import of cargo proteins into Vid vesicles in the vacuole dependent degradation pathway.

  2. Unfolded protein response and activated degradative pathways regulation in GNE myopathy.

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    Honghao Li

    Full Text Available Although intracellular beta amyloid (Aβ accumulation is known as an early upstream event in the degenerative course of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE myopathy, the process by which Aβdeposits initiate various degradative pathways, and their relationship have not been fully clarified. We studied the possible secondary responses after amyloid beta precursor protein (AβPP deposition including unfolded protein response (UPR, ubiquitin proteasome system (UPS activation and its correlation with autophagy system. Eight GNE myopathy patients and five individuals with normal muscle morphology were included in this study. We performed immunofluorescence and immunoblotting to investigate the expression of AβPP, phosphorylated tau (p-tau and endoplasmic reticulum molecular chaperones. Proteasome activities were measured by cleavage of fluorogenic substrates. The expression of proteasome subunits and linkers between proteasomal and autophagy systems were also evaluated by immunoblotting and relative quantitative real-time RT-PCR. Four molecular chaperones, glucose-regulated protein 94 (GRP94, glucose-regulated protein 78 (GRP78, calreticulin and calnexin and valosin containing protein (VCP were highly expressed in GNE myopathy. 20S proteasome subunits, three main proteasome proteolytic activities, and the factors linking UPS and autophagy system were also increased. Our study suggests that AβPP deposition results in endoplasmic reticulum stress (ERS and highly expressed VCP deliver unfolded proteins from endoplasmic reticulum to proteosomal system which is activated in endoplasmic reticulum associated degradation (ERAD in GNE myopathy. Excessive ubiquitinated unfolded proteins are exported by proteins that connect UPS and autophagy to autophagy system, which is activated as an alternative pathway for degradation.

  3. Enzymatic description of the anhydrofructose pathway of glycogen degradation. I

    DEFF Research Database (Denmark)

    Yu, Shukun; Refdahl, Charlotte; Lundt, Inge

    2004-01-01

    The anhydrofructose pathway describes the degradation of glycogen and starch to metabolites via 1,5-anhydro-D-fructose (1,5AnFru). The enzyme catalyzing the first reaction step of this pathway, i.e., a-1,4-glucan lyase (EC 4.2.1.13), has been purified, cloned and characterized from fungi and red...... algae in our laboratory earlier. In the present study, two 1,5AnFru metabolizing enzymes were discovered in the fungus Anthracobia melaloma for the formation of ascopyrone P (APP), a fungal secondary metabolite exhibiting antibacterial and antioxidant activity. These are 1,5AnFru dehydratase (AFDH...

  4. Towards a Green Economy. Pathways to Sustainable Development and Poverty Eradication. A Synthesis for Policy Makers

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2011-07-01

    Nearly 20 years after the Earth Summit, nations are again on the Road to Rio, but in a world very different and very changed from that of 1992. Then we were just glimpsing some of the challenges emerging across the planet from climate change and the loss of species to desertification and land degradation. Today many of those seemingly far off concerns are becoming a reality with sobering implications for not only achieving the UN's Millennium Development Goals, but challenging the very opportunity for close to seven billion people - rising to nine billion by 2050 - to be able to thrive, let alone survive. Rio 1992 did not fail the world - far from it. It provided the vision and important pieces of the multilateral machinery to achieve a sustainable future. But this will only be possible if the environmental and social pillars of sustainable development are given equal footing with the economic one: where the often invisible engines of sustainability, from forests to freshwaters, are also given equal if not greater weight in development and economic planning. Towards a Green Economy is among UNEP's key contributions to the Rio+20 process and the overall goal of addressing poverty and delivering a sustainable 21st century. The report makes a compelling economic and social case for investing two per cent of global GDP in greening ten central sectors of the economy in order to shift development and unleash public and private capital flows onto a low-carbon, resource-efficient path. Such a transition can catalyse economic activity of at least a comparable size to business as usual, but with a reduced risk of the crises and shocks increasingly inherent in the existing model. New ideas are by their very nature disruptive, but far less disruptive than a world running low on drinking water and productive land, set against the backdrop of climate change, extreme weather events and rising natural resource scarcities. A green economy does not favour one political

  5. Kynurenine pathway in psychosis: evidence of increased tryptophan degradation.

    LENUS (Irish Health Repository)

    Barry, Sandra

    2009-05-01

    The kynurenine pathway of tryptophan degradation may serve to integrate disparate abnormalities heretofore identified in research aiming to elucidate the complex aetiopathogenesis of psychotic disorders. Post-mortem brain tissue studies have reported elevated kynurenine and kynurenic acid in the frontal cortex and upregulation of the first step of the pathway in the anterior cingulate cortex of individuals with schizophrenia. In this study, we examined kynurenine pathway activity by measuring tryptophan breakdown, a number of pathway metabolites and interferon gamma (IFN-gamma), which is the preferential activator of the first-step enzyme, indoleamine dioxygenase (IDO), in the plasma of patients with major psychotic disorder. Plasma tryptophan, kynurenine pathway metabolites were measured using high-performance liquid chromatography (HPLC) in 34 patients with a diagnosis on the psychotic spectrum (schizophrenia or schizoaffective disorder) and in 36 healthy control subjects. IFN-gamma was measured using enzyme-linked immunosorbent assay (ELISA). The mean tryptophan breakdown index (kynurenine\\/tryptophan) was significantly higher in the patient group compared with controls (P < 0.05). IFN-gamma measures did not differ between groups (P = 0.23). No relationship was found between measures of psychopathology, symptom severity and activity in the first step in the pathway. A modest correlation was established between the tryptophan breakdown index and illness duration. These results provide evidence for kynurenine pathway upregulation, specifically involving the first enzymatic step, in patients with major psychotic disorder. Increased tryptophan degradation in psychoses may have potential consequences for the treatment of these disorders by informing the development of novel therapeutic compounds.

  6. Degradation of toluene-2,4-diamine by persulphate: kinetics, intermediates and degradation pathway.

    Science.gov (United States)

    Jiang, Yong-hai; Zhang, Jin-bao; Xi, Bei-dou; An, Da; Yang, Yu; Li, Ming-xiao

    2015-01-01

    In this study, the degradation of toluene-2,4-diamine (TDA) by persulphate (PS) in an aqueous solution at near-neutral pH was examined. The result showed that the degradation rate of TDA increased with increasing PS concentrations. The optimal dosage of PS in the reaction system was determined by efficiency indicator (I) coupling in the consumption of PS and decay half-life of TDA. Calculation showed that 0.74 mM of PS was the most effective dosage for TDA degradation, at that level the maximum I of 24.51 was obtained. PS can oxidize TDA for an extended reaction time period. Under neutral condition without activation, four degradation intermediates, 2,4-diamino-3-hydroxy-5-sulfonicacidtoluene, 2,4-diaminobenzaldehyde, 2,4-bis(vinylamino)benzaldehyde and 3,5-diamino-4-hydroxy-2-pentene, were identified by high-performance liquid chromatography-mass spectrometry. The tentative degradation pathway of TDA was proposed as well. It was found that hydroxyl radical played an important role in degradation of TDA with the activation of Fe2+, whereas PS anion and sulphate radicals were responsible for the degradation without activation of Fe2+.

  7. Degradation of phenazone in aqueous solution with ozone: influencing factors and degradation pathways.

    Science.gov (United States)

    Miao, Heng-Feng; Cao, Meng; Xu, Dan-Yao; Ren, Hong-Yan; Zhao, Ming-Xing; Huang, Zhen-Xing; Ruan, Wen-Quan

    2015-01-01

    Oxidation kinetics and degradation pathways of phenazone (an analgesic and antipyretic drug) upon reaction with O3 were investigated. Kinetic studies on degradation of phenazone were carried out under different operating conditions such as temperature, pH, anions and H2O2 addition. Results showed that the degradation followed the pseudo-first-order kinetic model. The reaction rate constant (kobs) of phenazone reached the maximum at 20 °C (9.653×10(-3) s(-1)). The presence of NO3(-) could enhance the degradation rate, while the addition of HCO3(-), SO4(2)(-), Cl(-) and the rise of pH showed negative effects on the ozonation of phenazone. H2O2 addition increased the phenazone degradation efficiency by 45.9% with the optimal concentration of 0.135 mM. Reaction by-products were evaluated by UPLC-Q-TOF-MS, which allowed the identification of a total of 10 by-products. The transformation pathways of phenazone ozonation consisted mainly of electrophilic addition and substitution, pyrazole ring opening, hydroxylation, dephenylization and coupling. The toxicity of these intermediate products showed that they are expected not to be more toxic than phenazone, with the exception of P7 (aniline) and P10 (1,5-dimethyl-4-((1-methyl-2-phenylhydrazinyl)methoxy)-2-phenyl-1H-pyrazol-3(2H)-one).

  8. Capsaicin-sensitive afferentation represents an indifferent defensive pathway from eradication in patients with H.pylori gastritis

    Institute of Scientific and Technical Information of China (English)

    Lilla; Lakner; András; Dmtr; Csaba; Tóth; Imre; L; Szabó; gnes; Meczker; Rebeka; Hajós; László; Kereskai; Gyrgy; Szekeres; Zoltán; Dbrnte; Gyula; Mózsik

    2011-01-01

    AIM:To study the role of capsaicin-sensitive afferent nerves in Helicobacter pylori (H.pylori) positive chronic gastritis before and after eradication.METHODS:Gastric biopsy samples were obtained from corpus and antrum mucosa of 20 healthy human subjects and 18 patients with H.pylori positive chronic gastritis (n=18) before and after eradication.Tradi-tional gastric mucosal histology (and Warthin-Starry silver impregnation) and special histochemical examina-tions were carried out.Immunohistochemistry for cap-saicin receptor (TRVP1),calcitonin gene-related peptide (CGRP) and substance P (SP) were carried out by the labeled polymer immunohistological method (Lab VisionCo.,USA) using polyclonal rabbit and rat monoclonal antibodies (Abcam Ltd.,UK).RESULTS:Eradication treatment was successful in 16 patients (89%).Seven patients (7/18,39%) re-mained with moderate complaints,meanwhile 11 pa-tients (11/28,61%) had no complaints.At histological evaluation,normal gastric mucosa was detected in 4 patients after eradication treatment (4/18,22%),and moderate chronic gastritis could be seen in 14 (14/18,78%) patients.Positive immuno-staining for capsaicin receptor was seen in 35% (7/20) of controls,89% (16/18,P < 0.001) in patients before and 72% (13/18,P < 0.03) after eradication.CGRP was positive in 40% (8/20) of controls,and in 100% (18/18,P < 0.001) of patients before and in 100% (18/18,P < 0.001) after eradication.The immune-staining of gastric mucosa for substance-P was positive in 25% (5/20) of healthy con-trols,and in 5.5% (3/18,P > 0.05) of patients before and in 0% of patients (0/18,P > 0.05) after H.pylori eradication.CONCLUSION:Distibution of TRVP1 and CGRP is altered during the development of H.pylori positive chronic gastritis.The immune-staining for TRVP1,CGRP and SP rwemained unchanged before and after H.py-lori eradication treatment.The capsaicin-sensitive affer-entation is an independent from the eradication treat-ment.The 6 wk time period might not be enough

  9. The delicate balance between secreted protein folding and endoplasmic reticulum-associated degradation in human physiology.

    Science.gov (United States)

    Guerriero, Christopher J; Brodsky, Jeffrey L

    2012-04-01

    Protein folding is a complex, error-prone process that often results in an irreparable protein by-product. These by-products can be recognized by cellular quality control machineries and targeted for proteasome-dependent degradation. The folding of proteins in the secretory pathway adds another layer to the protein folding "problem," as the endoplasmic reticulum maintains a unique chemical environment within the cell. In fact, a growing number of diseases are attributed to defects in secretory protein folding, and many of these by-products are targeted for a process known as endoplasmic reticulum-associated degradation (ERAD). Since its discovery, research on the mechanisms underlying the ERAD pathway has provided new insights into how ERAD contributes to human health during both normal and diseases states. Links between ERAD and disease are evidenced from the loss of protein function as a result of degradation, chronic cellular stress when ERAD fails to keep up with misfolded protein production, and the ability of some pathogens to coopt the ERAD pathway. The growing number of ERAD substrates has also illuminated the differences in the machineries used to recognize and degrade a vast array of potential clients for this pathway. Despite all that is known about ERAD, many questions remain, and new paradigms will likely emerge. Clearly, the key to successful disease treatment lies within defining the molecular details of the ERAD pathway and in understanding how this conserved pathway selects and degrades an innumerable cast of substrates.

  10. Proteogenomic Characterization of Monocyclic Aromatic Hydrocarbon Degradation Pathways in the Aniline-Degrading Bacterium Burkholderia sp. K24.

    Directory of Open Access Journals (Sweden)

    Sang-Yeop Lee

    Full Text Available Burkholderia sp. K24, formerly known as Acinetobacter lwoffii K24, is a soil bacterium capable of utilizing aniline as its sole carbon and nitrogen source. Genomic sequence analysis revealed that this bacterium possesses putative gene clusters for biodegradation of various monocyclic aromatic hydrocarbons (MAHs, including benzene, toluene, and xylene (BTX, as well as aniline. We verified the proposed MAH biodegradation pathways by dioxygenase activity assays, RT-PCR, and LC/MS-based quantitative proteomic analyses. This proteogenomic approach revealed four independent degradation pathways, all converging into the citric acid cycle. Aniline and p-hydroxybenzoate degradation pathways converged into the β-ketoadipate pathway. Benzoate and toluene were degraded through the benzoyl-CoA degradation pathway. The xylene isomers, i.e., o-, m-, and p-xylene, were degraded via the extradiol cleavage pathways. Salicylate was degraded through the gentisate degradation pathway. Our results show that Burkholderia sp. K24 possesses versatile biodegradation pathways, which may be employed for efficient bioremediation of aniline and BTX.

  11. Hydrolytic and oxidative degradation of electrospun supramolecular biomaterials: In vitro degradation pathways.

    Science.gov (United States)

    Brugmans, M C P; Sӧntjens, S H M; Cox, M A J; Nandakumar, A; Bosman, A W; Mes, T; Janssen, H M; Bouten, C V C; Baaijens, F P T; Driessen-Mol, A

    2015-11-01

    The emerging field of in situ tissue engineering (TE) of load bearing tissues places high demands on the implanted scaffolds, as these scaffolds should provide mechanical stability immediately upon implantation. The new class of synthetic supramolecular biomaterial polymers, which contain non-covalent interactions between the polymer chains, thereby forming complex 3D structures by self assembly. Here, we have aimed to map the degradation characteristics of promising (supramolecular) materials, by using a combination of in vitro tests. The selected biomaterials were all polycaprolactones (PCLs), either conventional and unmodified PCL, or PCL with supramolecular hydrogen bonding moieties (either 2-ureido-[1H]-pyrimidin-4-one or bis-urea units) incorporated into the backbone. As these materials are elastomeric, they are suitable candidates for cardiovascular TE applications. Electrospun scaffold strips of these materials were incubated with solutions containing enzymes that catalyze hydrolysis, or solutions containing oxidative species. At several time points, chemical, morphological, and mechanical properties were investigated. It was demonstrated that conventional and supramolecular PCL-based polymers respond differently to enzyme-accelerated hydrolytic or oxidative degradation, depending on the morphological and chemical composition of the material. Conventional PCL is more prone to hydrolytic enzymatic degradation as compared to the investigated supramolecular materials, while, in contrast, the latter materials are more susceptible to oxidative degradation. Given the observed degradation pathways of the examined materials, we are able to tailor degradation characteristics by combining selected PCL backbones with additional supramolecular moieties. The presented combination of in vitro test methods can be employed to screen, limit, and select biomaterials for pre-clinical in vivo studies targeted to different clinical applications.

  12. ARTS and Siah Collaborate in a Pathway for XIAP Degradation

    Science.gov (United States)

    Garrison, Jason B.; Correa, Ricardo G.; Gerlic, Motti; Yip, Kenneth W.; Krieg, Andreas; Tamble, Craig M.; Shi, Ranxin; Welsh, Kate; Duggineni, Srinivas; Huang, Ziwei; Ren, Keqin; Du, Chunying; Reed, John C.

    2010-01-01

    SUMMARY ARTS (Apoptosis-Related protein in the TGF-β Signaling pathway) is a mitochondrial protein that binds XIAP (X-linked Inhibitor of Apoptosis Protein) upon entering the cytosol, thus promoting cell death. Expression of ARTS is lost in some malignancies. Here we show that ARTS binds to XIAP at BIR1, a domain distinct from the caspase-binding sites. Furthermore, ARTS interacts with the E3 ligase Siah-1 (seven in absentia homolog 1) to induce ubiquitination and degradation of XIAP. Cells lacking either Siah or ARTS contain higher steady-state levels of XIAP. Thus, ARTS serves as an adapter to bridge Siah-1 to XIAP, targeting it for destruction. PMID:21185211

  13. Biotransformation of nitrobenzene by bacteria containing toluene degradative pathways

    Energy Technology Data Exchange (ETDEWEB)

    Haigler, B.E.; Spain, J.C. (Air Force Civil Engineering Support Agency, Tyndall AFB, FL (United States))

    1991-11-01

    Nonpolar nitroaromatic compounds have been considered resistant to attack by oxygenases because of the electron withdrawing properties of the nitro group. The authors have investigate the ability of seven bacterial strains containing toluene degradative pathways to oxidize nitrobenzene. Cultures were induced with toluene vapor prior to incubation with nitrobenzene, and products were identified by high-performance liquid chromatography and gas chromatography-mass spectrometry. Pseudomonas cepacia G4 and a strain of Pseudomonas harboring the TOL plasmid (pTN2) did not transform nitrobenzene. Cells of Pseudomonas putida F1 and Pseudomonas sp. strain JS150 converted nitrobenzene to 3-nitrocatechol. Transformation of nitrobenzene in the presence of {sup 18}O{sub 2} indicated that the reaction in JS150 involved the incorporation of both atoms of oxygen in the 3-nitrocatechol, which suggests a dioxygenase mechanism. P. putida 39/D, a mutant strain of P. putida F1, converted nitrobenzene to a compound tentatively identified as cis-1, 2-dihydroxy-3-nitrocyclohexa-3, 5-diene. This compound was rapidly converted to 3-nitrocatechol by cells of strain JS150. Cultures of Pseudomonas mendocina KR-1 converted nitrobenzene to a mixture of 3- and 4-nitrophenol (10 and 63%, respectively). Pseudomonas pickettii PKO1 converted nitrobenzene to 3- and 4-nitrocatechol via 3- and 4-nitrophenol. The nitrocatechols were slowly degraded to unidentified metabolites. Nitrobenzene did not serve as an inducer for the enzymes that catalyzed its oxidation.

  14. A SEL1L mutation links a canine progressive early-onset cerebellar ataxia to the endoplasmic reticulum-associated protein degradation (ERAD machinery.

    Directory of Open Access Journals (Sweden)

    Kaisa Kyöstilä

    Full Text Available Inherited ataxias are characterized by degeneration of the cerebellar structures, which results in progressive motor incoordination. Hereditary ataxias occur in many species, including humans and dogs. Several mutations have been found in humans, but the genetic background has remained elusive in dogs. The Finnish Hound suffers from an early-onset progressive cerebellar ataxia. We have performed clinical, pathological, and genetic studies to describe the disease phenotype and to identify its genetic cause. Neurological examinations on ten affected dogs revealed rapidly progressing generalized cerebellar ataxia, tremors, and failure to thrive. Clinical signs were present by the age of 3 months, and cerebellar shrinkage was detectable through MRI. Pathological and histological examinations indicated cerebellum-restricted neurodegeneration. Marked loss of Purkinje cells was detected in the cerebellar cortex with secondary changes in other cortical layers. A genome-wide association study in a cohort of 31 dogs mapped the ataxia gene to a 1.5 Mb locus on canine chromosome 8 (p(raw = 1.1x10(-7, p(genome = 7.5x10(-4. Sequencing of a functional candidate gene, sel-1 suppressor of lin-12-like (SEL1L, revealed a homozygous missense mutation, c.1972T>C; p.Ser658Pro, in a highly conserved protein domain. The mutation segregated fully in the recessive pedigree, and a 10% carrier frequency was indicated in a population cohort. SEL1L is a component of the endoplasmic reticulum (ER-associated protein degradation (ERAD machinery and has not been previously associated to inherited ataxias. Dysfunctional protein degradation is known to cause ER stress, and we found a significant increase in expression of nine ER stress responsive genes in the cerebellar cortex of affected dogs, supporting the pathogenicity of the mutation. Our study describes the first early-onset neurodegenerative ataxia mutation in dogs, establishes an ERAD-mediated neurodegenerative

  15. Fenton degradation of Cartap hydrochloride: identification of the main intermediates and the degradation pathway.

    Science.gov (United States)

    Tian, Kaixun; Ming, Cuixiang; Dai, Youzhi; Honore Ake, Kouassi Marius

    2015-01-01

    The advanced oxidation of Cartap hydrochloride (Cartap) promoted by the Fenton system in an aqueous medium was investigated. Based on total organic carbon, chemical oxygen demand and high-performance liquid chromatography, the oxidation of Cartap is quite efficient by the Fenton system. Its long chain is easily destroyed, but the reaction does not proceed to complete mineralization. Ion chromatography detection indicated the formation of acetic acid, propionic acid, formic acid, nitrous acid and sulfuric acid in the reaction mixtures. Further evidence of nitrogen monoxide and sulfur dioxide formation was obtained by using a flue gas analyzer. Monitoring by gas chromatograph-mass spectrometer demonstrated the formation of oxalic acid, ethanol, carbon dioxide, and L-alanine ethylamide. Based on these experimental results, plausible degradation pathways for Cartap mineralization in an aqueous medium by the Fenton system are proposed.

  16. Mechanochemical degradation of tetrabromobisphenol A: Performance, products and pathway

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Kunlun; Huang, Jun; Zhang, Wang; Yu, Yunfei; Deng, Shubo [State Key Joint Laboratory of Environment Simulation and Pollution Control (SKLESPC), School of Environment, POPs Research Center, Tsinghua University, Beijing 100084 (China); Yu, Gang, E-mail: yg-den@tsinghua.edu.cn [State Key Joint Laboratory of Environment Simulation and Pollution Control (SKLESPC), School of Environment, POPs Research Center, Tsinghua University, Beijing 100084 (China)

    2012-12-15

    Highlights: Black-Right-Pointing-Pointer Fe + SiO{sub 2} shows better performance than CaO in mechanochemical destruction of TBBPA. Black-Right-Pointing-Pointer Nonhazardous inorganic carbon and soluble bromide were the final products. Black-Right-Pointing-Pointer Raman and FTIR imply the generation of inorganic carbon and removal of bromine atom. Black-Right-Pointing-Pointer Tri-BBPA, bi-BBPA, mono-BBPA, BPA were the main intermediates during ball milling. Black-Right-Pointing-Pointer The bromine was balanced and the degradation pathway was proposed. - Abstract: Tetrabromobisphenol A (TBBPA) is the most widely used brominated flame retardant (BFR), which has received more and more concerns due to its high lipophilicity, persistency and endocrine disrupting property in the environment. Considering the possible need for the safe disposal of TBBPA containing wastes in the future, the potential of mechanochemical (MC) destruction as a promising non-combustion technology was investigated in this study. TBBPA was co-ground with calcium oxide (CaO) or the mixture of iron powder and quartz sand (Fe + SiO{sub 2}) in a planetary ball mill at room temperature. The method of Fe + SiO{sub 2} destructed over 98% of initial TBBPA after 3 h and acquired 95% debromination rate after 5 h, which showed a better performance than the CaO method. Raman spectra and Fourier transform infrared spectroscopy (FTIR) demonstrated the generation of inorganic carbon with the disappearance of benzene ring and C-Br bond, indicating the carbonization and debromination process during mechanochemical reaction. LC-MS-MS screening showed that the intermediates of the treatment with Fe + SiO{sub 2} were tri-, bi-, mono-brominated BPA, BPA and other fragments. Finally all the intermediates were also destroyed after 5 h grinding. The bromine balance was calculated and a possible reaction pathway was proposed.

  17. Complementary roles of intracellular and pericellular collagen degradation pathways in vivo

    DEFF Research Database (Denmark)

    Wagenaar-Miller, Rebecca A; Engelholm, Lars H; Gavard, Julie

    2007-01-01

    these two pathways is unclear and even controversial. Here we show that intracellular and pericellular collagen turnover pathways have complementary roles in vivo. Individual deficits in intracellular collagen degradation (urokinase plasminogen activator receptor-associated protein/Endo180 ablation......Collagen degradation is essential for cell migration, proliferation, and differentiation. Two key turnover pathways have been described for collagen: intracellular cathepsin-mediated degradation and pericellular collagenase-mediated degradation. However, the functional relationship between......) or pericellular collagen degradation (membrane type 1-matrix metalloproteinase ablation) were compatible with development and survival. Their combined deficits, however, synergized to cause postnatal death by severely impairing bone formation. Interestingly, this was mechanistically linked to the proliferative...

  18. Degradation pathway of 2-chloroethanol in Pseudomonas stutzeri strain JJ under denitrifying conditions

    NARCIS (Netherlands)

    Dijk, J.A.; Gerritse, J.; Schraa, G.; Stams, A.J.M.

    2004-01-01

    The pathway of 2-chloroethanol degradation in the denitrifying Pseudomonas stutzeri strain JJ was investigated. In cell-free extracts, activities of a phenazine methosulfate (PMS)-dependent chloroethanol dehydrogenase, an NAD-dependent chloroacetaldehyde dehydrogenase, and a chloroacetate dehalogena

  19. Modeling position-specific isotope fractionation of organic micropollutants degradation via different reaction pathways

    DEFF Research Database (Denmark)

    Jin, Biao; Rolle, Massimo

    : dichlorobenzamide (BAM), isoproturon (IPU) and diclofenac (DCF). The model successfully reproduces the multi-element isotope data, and precisely captures the dual element isotope trends, characterizing the different degradation pathways. Besides illustrating the model capability of mechanistic evaluation...

  20. Biochemical and physiological characterisation of the purine degradation pathway in plants

    OpenAIRE

    Werner, Andrea

    2013-01-01

    Plant growth is often limited by nitrogen availability in the soil. Not only do plants depend on efficient nitrogen uptake, they also require effective means to internally redistribute nitrogen during every stage of development. The purine degradation pathway contributes to this nitrogen recycling in plants. In tropical legumes it is also of central importance to the plants’ nitrogen supply under nitrogen-fixing conditions. This is the first time that the complete ureide degradation pathway h...

  1. Degradation of diclofenac by UV-activated persulfate process: Kinetic studies, degradation pathways and toxicity assessments.

    Science.gov (United States)

    Lu, Xian; Shao, Yisheng; Gao, Naiyun; Chen, Juxiang; Zhang, Yansen; Xiang, Huiming; Guo, Youluo

    2017-03-21

    Diclofenac (DCF) is the frequently detected non-steroidal pharmaceuticals in the aquatic environment. In this study, the degradation of DCF was evaluated by UV-254nm activated persulfate (UV/PS). The degradation of DCF followed the pseudo first-order kinetics pattern. The degradation rate constant (kobs) was accelerated by UV/PS compared to UV alone and PS alone. Increasing the initial PS dosage or solution pH significantly enhanced the degradation efficiency. Presence of various natural water constituents had different effects on DCF degradation, with an enhancement or inhibition in the presence of inorganic anions (HCO3(-) or Cl(-)) and a significant inhibition in the presence of NOM. In addition, preliminary degradation mechanisms and major products were elucidated using LC-MS/MS. Hydroxylation, decarbonylation, ring-opening and cyclation reaction involving the attack of SO4(•)(-) or other substances, were the main degradation mechanism. TOC analyzer and Microtox bioassay were employed to evaluate the mineralization and cytotoxicity of solutions treated by UV/PS at different times, respectively. Limited elimination of TOC (32%) was observed during the mineralization of DCF. More toxic degradation products and their related intermediate species were formed, and the UV/PS process was suitable for removing the toxicity. Of note, longer degradation time may be considered for the final toxicity removal.

  2. Degradation Pathway for Eplerenone by Validated Stability Indicating UP-LC Method

    OpenAIRE

    Kondru Sudhakar Babu; Venkataramanna Madireddy; Venkata Somaraju Indukuri

    2012-01-01

    Degradation pathway for eplerenone is established as per ICH recommendations by validated and stability-indicating reverse phase liquid chromatographic method. Eplerenone is subjected to stress conditions of acid, base, oxidation, and thermal and photolysis. Significant degradation is observed in acid and base stress conditions. Four impurities are studied and the major degradant (RRT about 0.31) was identified by LC-MS and spectral analysis. The stress samples are assayed against a qualified...

  3. MAPKs are essential upstream signaling pathways in proteolytic cartilage degradation--divergence in pathways leading to aggrecanase and MMP-mediated articular cartilage degradation

    DEFF Research Database (Denmark)

    Sondergaard, B-C; Schultz, N; Madsen, S H;

    2010-01-01

    Matrix metalloproteinases (MMPs) and aggrecanases are essential players in cartilage degradation. However, the signaling pathways that results in MMP and/or aggrecanase synthesis and activation are not well understood. We investigated the molecular events leading to MMP- and aggrecanase-mediated ...

  4. Transmembrane helix hydrophobicity is an energetic barrier during the retrotranslocation of integral membrane ERAD substrates

    Science.gov (United States)

    Guerriero, Christopher J.; Reutter, Karl-Richard; Augustine, Andrew A.; Preston, G. Michael; Weiberth, Kurt F.; Mackie, Timothy D.; Cleveland-Rubeor, Hillary C.; Bethel, Neville P.; Callenberg, Keith M.; Nakatsukasa, Kunio; Grabe, Michael; Brodsky, Jeffrey L.

    2017-01-01

    Integral membrane proteins fold inefficiently and are susceptible to turnover via the endoplasmic reticulum–associated degradation (ERAD) pathway. During ERAD, misfolded proteins are recognized by molecular chaperones, polyubiquitinated, and retrotranslocated to the cytoplasm for proteasomal degradation. Although many aspects of this pathway are defined, how transmembrane helices (TMHs) are removed from the membrane and into the cytoplasm before degradation is poorly understood. In this study, we asked whether the hydrophobic character of a TMH acts as an energetic barrier to retrotranslocation. To this end, we designed a dual-pass model ERAD substrate, Chimera A*, which contains the cytoplasmic misfolded domain from a characterized ERAD substrate, Sterile 6* (Ste6p*). We found that the degradation requirements for Chimera A* and Ste6p* are similar, but Chimera A* was retrotranslocated more efficiently than Ste6p* in an in vitro assay in which retrotranslocation can be quantified. We then constructed a series of Chimera A* variants containing synthetic TMHs with a range of ΔG values for membrane insertion. TMH hydrophobicity correlated inversely with retrotranslocation efficiency, and in all cases, retrotranslocation remained Cdc48p dependent. These findings provide insight into the energetic restrictions on the retrotranslocation reaction, as well as a new computational approach to predict retrotranslocation efficiency. PMID:28539401

  5. GPG-NH2 acts via the metabolite αHGA to target HIV-1 Env to the ER-associated protein degradation pathway

    Directory of Open Access Journals (Sweden)

    Vahlne Anders

    2010-03-01

    Full Text Available Abstract Background The synthetic peptide glycyl-prolyl-glycine amide (GPG-NH2 was previously shown to abolish the ability of HIV-1 particles to fuse with the target cells, by reducing the content of the viral envelope glycoprotein (Env in progeny HIV-1 particles. The loss of Env was found to result from GPG-NH2 targeting the Env precursor protein gp160 to the ER-associated protein degradation (ERAD pathway during its maturation. However, the anti-viral effect of GPG-NH2 has been shown to be mediated by its metabolite α-hydroxy-glycineamide (αHGA, which is produced in the presence of fetal bovine serum, but not human serum. In accordance, we wanted to investigate whether the targeting of gp160 to the ERAD pathway by GPG-NH2 was attributed to its metabolite αHGA. Results In the presence of fetal bovine serum, GPG-NH2, its intermediary metabolite glycine amide (G-NH2, and final metabolite αHGA all induced the degradation of gp160 through the ERAD pathway. However, when fetal bovine serum was replaced with human serum only αHGA showed an effect on gp160, and this activity was further shown to be completely independent of serum. This indicated that GPG-NH2 acts as a pro-drug, which was supported by the observation that it had to be added earlier to the cell cultures than αHGA to induce the degradation of gp160. Furthermore, the substantial reduction of Env incorporation into HIV-1 particles that occurs during GPG-NH2 treatment was also achieved by treating HIV-1 infected cells with αHGA. Conclusions The previously observed specificity of GPG-NH2 towards gp160 in HIV-1 infected cells, resulting in the production of Env (gp120/gp41 deficient fusion incompetent HIV-1 particles, was most probably due to the action of the GPG-NH2 metabolite αHGA.

  6. Bioenergetics and pathway of acid blue 113 degradation by Staphylococcus lentus.

    Science.gov (United States)

    Sekar, Sudharshan; Mahadevan, Surianarayanan; Shanmugam, Bhuvanesh Kumar; Mandal, Asit Baran

    2012-01-01

    Bioreaction calorimetric studies of degradation of the dye acid blue 113 by Staphylococcus lentus are reported for the first time. The heat released during the dye degradation process can be successfully measured using reaction calorimeter. Power time and oxygen uptake rate (OUR) profile followed each other suggesting that heat profiles could monitor the progress of the dye degradation in biocalorimetry. The shifts observed in power-time profile indicated three distinct phases of the bioprocess indicating simultaneous utilization of glucose (primary) and dye (secondary carbon source). Secretion of azoreductase enzyme enhanced the degradation process. Optimization of aeration and agitation rates was observed to be vital to efficient dye degradation. The degradative pathway for acid blue 113 by S. lentus was delineated via high-performance liquid chromatography (HPLC), Fourier transform infrared spectroscopy (FT-IR), and gas chromatography coupled with mass spectrometry (GC-MS) analyses. Interestingly the products of degradation were found to have low toxicity, as per cytotoxicity measurements.

  7. Degradation pathway of malachite green in a novel dual-tank photoelectrochemical catalytic reactor

    Energy Technology Data Exchange (ETDEWEB)

    Diao, Zenghui [Department of Environmental Engineering, Jinan University, Guangzhou 510630 (China); School of Environmental Science and Engineering, Sun Yat-Sen University, Guangzhou 510275 (China); Li, Mingyu, E-mail: tlimy@jnu.edu.cn [Department of Environmental Engineering, Jinan University, Guangzhou 510630 (China); Zeng, Fanyin; Song, Lin [Department of Environmental Engineering, Jinan University, Guangzhou 510630 (China); Qiu, Rongliang [School of Environmental Science and Engineering, Sun Yat-Sen University, Guangzhou 510275 (China)

    2013-09-15

    Highlights: • A novel dual-tank photoelectrochemical catalytic reactor was designed. • Malachite green degraded in bipolar double-effect mode. • Salt bridge replaced by a cation exchange membrane in the reactor. • Degradation pathways of malachite green in the cathode and anode tanks were similar. -- Abstract: A novel dual-tank photoelectrochemical catalytic reactor was designed to investigate the degradation pathway of malachite green. A thermally formed TiO{sub 2}/Ti thin film electrode was used as photoanode, graphite was used as cathode, and a saturated calomel electrode was employed as the reference electrode in the reactor. In the reactor, the anode and cathode tanks were connected by a cation exchange membrane. Results showed that the decolorization ratio of malachite green in the anode and cathode was 98.5 and 96.5% after 120 min, respectively. Malachite green in the two anode and cathode tanks was oxidized, achieving the bipolar double effect. Malachite green in both the anode and cathode tanks exhibited similar catalytic degradation pathways. The double bond of the malachite green molecule was attacked by strong oxidative hydroxyl radicals, after which the organic compound was degraded by the two pathways into 4,4-bis(dimethylamino) benzophenone, 4-(dimethylamino) benzophenone, 4-(dimethylamino) phenol, and other intermediate products. Eventually, malachite green was degraded into oxalic acid as a small molecular organic acid, which was degraded by processes such as demethylation, deamination, nitration, substitution, addition, and other reactions.

  8. Characterization of the novel dimethyl sulfide-degrading bacterium Alcaligenes sp. SY1 and its biochemical degradation pathway

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Yiming; Qiu, Jiguo; Chen, Dongzhi; Ye, Jiexu; Chen, Jianmeng, E-mail: jchen@zjut.edu.cn

    2016-03-05

    Highlights: • A novel efficient DMS-degrading bacterium Alcaligenes sp. SY1 was identified. • A RSM was applied to optimize incubation condition of Alcaligenes sp. SY1. • SIP was applied as C{sup 13} labelled DMS to trace intermediates during DMS degradation. • Kinetics of DMS degradation via batch experiment was revealed. • Carbon and sulfur balance were analyzed during DMS degradation process. - Abstract: Recently, the biodegradation of volatile organic sulfur compounds (VOSCs) has become a burgeoning field, with a growing focus on the reduction of VOSCs. The reduction of VOSCs encompasses both organic emission control and odor control. Herein, Alcaligenes sp. SY1 was isolated from active sludge and found to utilize dimethyl sulfide (DMS) as a growth substrate in a mineral salt medium. Response surface methodology (RSM) analysis was applied to optimize the incubation conditions. The following conditions for optimal degradation were identified: temperature 27.03 °C; pH 7.80; inoculum salinity 0.84%; and initial DMS concentration 1585.39 μM. Under these conditions, approximately 99% of the DMS was degraded within 30 h of incubation. Two metabolic compounds were detected and identified by gas chromatography–mass spectrometry (GC–MS): dimethyl disulfide (DMDS) and dimethyl trisulfide (DMTS). The DMS degradation kinetics for different concentrations were evaluated using the Haldane–Andrews model and the pseudo first-order model. The maximum specific growth rate and degradation rate of Alcaligenes sp. SY1 were 0.17 h{sup −1} and 0.63 gs gx{sup −1} h{sup −1}. A possible degradation pathway is proposed, and the results suggest that Alcaligenes sp. SY1 has the potential to control odor emissions under aerobic conditions.

  9. A luminal flavoprotein in endoplasmic reticulum-associated degradation

    DEFF Research Database (Denmark)

    Riemer, Jan; Appenzeller-Herzog, Christian; Johansson, Linda

    2009-01-01

    The quality control system of the endoplasmic reticulum (ER) discriminates between native and nonnative proteins. The latter are degraded by the ER-associated degradation (ERAD) pathway. Whereas many cytosolic and membrane components of this system are known, only few luminal players have been id...

  10. PHOSPHOLIPIDS OF FIVE PSEUDOMONAD ARCHETYPES FOR DIFFERENT TOLUENE DEGRADATION PATHWAYS

    Science.gov (United States)

    Liquid chromatography/electrospray ionization/mass spectrometry (LC/ESI/MS) was used to determine phospholipid profiles for five reference pseudomonad strains harboring distinct toluene catabolic pathways: Pseudomonas putida mt-2, Pseudomonas putida F1, Burkholderia cepacia G4, B...

  11. Metabolic pathways for degradation of aromatic hydrocarbons by bacteria

    NARCIS (Netherlands)

    Ladino-Orjuela, G.; Gomes, E.; da Silva, R.; Salt, C.; Parsons, J.R.; de Voogt, W.P.

    2016-01-01

    The aim of this revision was to build an updated collection of information focused on the mechanisms and elements involved in metabolic pathways of aromatic hydrocarbons by bacteria. Enzymes as an expression of the genetic load and the type of electron acceptor available, as an environmental factor,

  12. Pathways for degradation of plastic polymers floating in the marine environment.

    Science.gov (United States)

    Gewert, Berit; Plassmann, Merle M; MacLeod, Matthew

    2015-09-01

    Each year vast amounts of plastic are produced worldwide. When released to the environment, plastics accumulate, and plastic debris in the world's oceans is of particular environmental concern. More than 60% of all floating debris in the oceans is plastic and amounts are increasing each year. Plastic polymers in the marine environment are exposed to sunlight, oxidants and physical stress, and over time they weather and degrade. The degradation processes and products must be understood to detect and evaluate potential environmental hazards. Some attention has been drawn to additives and persistent organic pollutants that sorb to the plastic surface, but so far the chemicals generated by degradation of the plastic polymers themselves have not been well studied from an environmental perspective. In this paper we review available information about the degradation pathways and chemicals that are formed by degradation of the six plastic types that are most widely used in Europe. We extrapolate that information to likely pathways and possible degradation products under environmental conditions found on the oceans' surface. The potential degradation pathways and products depend on the polymer type. UV-radiation and oxygen are the most important factors that initiate degradation of polymers with a carbon-carbon backbone, leading to chain scission. Smaller polymer fragments formed by chain scission are more susceptible to biodegradation and therefore abiotic degradation is expected to precede biodegradation. When heteroatoms are present in the main chain of a polymer, degradation proceeds by photo-oxidation, hydrolysis, and biodegradation. Degradation of plastic polymers can lead to low molecular weight polymer fragments, like monomers and oligomers, and formation of new end groups, especially carboxylic acids.

  13. 3'-5' RNA degradation pathways in human cells

    DEFF Research Database (Denmark)

    Lubas, Michal Szymon

    RNA synthesis and degradation are key steps in the regulation of gene expression in all living organisms. During the course of his PhD studies, Michal Lubas centred his research on the nuclear and cytoplasmic RNA turnover of both noncoding and coding RNAs in human cells. His proteomic studies...... of the cytoplasmic 3'-5' exoribonuclease hDIS3L2. Using low throughout and high throughput techniques, both in vivo and in vitro, he characterised the nuclease and disclosed the role of hDIS3L2 in cytoplasmic mRNA metabolism....

  14. Evolutions of microbial degradation pathways for parent xenobiotic and for its metabolites follow different schemes.

    Science.gov (United States)

    Chong, Nyuk-Min; Chang, Chun-Shuo; Tsai, Shiu-Ching

    2012-09-01

    The pathways used by microorganisms for the metabolism of every xenobiotic substrate are specific. The catabolism of a xenobiotic goes through a series of intermediate steps and lower intermediates (metabolites) appear in sequence. The structure of the metabolites can be similar to the parents due to kinship. The purposes of this study were to examine if the degradation pathways that were developed for a parent xenobiotic are effective to degrade the parent's lower metabolites, and if the reverse is true. The xenobiotic substrates, 2,4-dichlorophenoxyacetic acid (2,4-D, the parent xenobiotic) and its metabolite 2,4-dichlorophenol (2,4-DCP), were independently subjected to acclimation and degradation tests by the biomasses of mixed-culture activated sludge and a pure culture of Arthrobacter sp. Activated sludge and Arthrobacter sp. that were acclimated to 2,4-D effectively degraded 2,4-D and the lower metabolites of 2,4-D, typically 2,4-DCP. During the degradation of 2,4-D, accumulations of the lower metabolites of 2,4-D were not found. The degradation pathways acquired from acclimation to 2,4-D are effective for all the metabolites of 2,4-D. However, pathways acquired from acclimation to 2,4-DCP are not effective in the degradation of the parent 2,4-D. Microorganisms acclimated to 2,4-D evolve their degradation pathways by a scheme that is different from the scheme the microorganisms employ when they are acclimated to the metabolites of 2,4-D.

  15. Removal of 2,4-dichlorophenoxyacetic acid in aqueous solution by pulsed corona discharge treatment: Effect of different water constituents, degradation pathway and toxicity assay.

    Science.gov (United States)

    Singh, Raj Kamal; Philip, Ligy; Ramanujam, Sarathi

    2017-10-01

    A multiple pin-plane corona discharge reactor was used to generate plasma for the degradation of 2,4 dichlorophenoxyacetic acid (2,4-D) from the aqueous solution. The 2,4-D of concentration 1 mg/L was completely removed within 6 min of plasma treatment. Almost complete mineralization was achieved after the treatment time of 14 min for a 2,4-D concentration of 10 mg/L. Effects of different water constituents such as carbonates, nitrate, sulphate, chloride ions, natural organic matter (humic acids) and pH on 2,4-D degradation was studied. A significant antagonistic effect of carbonate and humic acid was observed, whereas, the effects of other ions were insignificant. A higher first order rate constant of 1.73 min(-1) was observed, which was significantly decreased in the presence of carbonate ions and humic acids. Also, a higher degradation of 2,4-D was observed in acidic pH conditions. Different 2,4-D intermediates were detected and the degradation pathway of 2,4-D in plasma treatment process was suggested. The toxicity of 10 mg/L 2,4-D was completely eradicated after 10 min of plasma treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Photocatalytic degradation of methylene blue with a nanocomposite system: synthesis, photocatalysis and degradation pathways.

    Science.gov (United States)

    Xia, Shengjie; Zhang, Lianyang; Pan, Guoxiang; Qian, Pingping; Ni, Zheming

    2015-02-21

    Three different composites, including a calcined FeOOH supported ZnAl layered double hydroxide (FeOOH-LDO), a calcined ZnAl layered double hydroxide (ZnAl-LDO) and a calcined ZnFeAl layered double hydroxide (ZnFeAl-LDO), were synthesized via a sol-gel method, and their activity for the visible light photocatalytic degradation of methylene blue (MB) was studied. The composites were characterized by PXRD, SEM, and BET techniques, confirming the formation of highly crystalline structures. The activity performance of MB degradation was in the following order: FeOOH-LDO (∼95%) > ZnFeAl-LDO (∼60%) > ZnAl-LDO (∼23%). In addition, a possible photocatalytic degradation reaction mechanism for MB was also proposed. Moreover, the frontier electron densities on the atoms of MB were calculated, which were in satisfactory agreement with the postulated mechanism.

  17. Aerobic Degradation of Dinitrotoluenes and Pathway for Bacterial Degradation of 2,6-Dinitrotoluene

    OpenAIRE

    Nishino, Shirley F.; Paoli, George C.; Spain, Jim C.

    2000-01-01

    An oxidative pathway for the mineralization of 2,4-dinitrotoluene (2,4-DNT) by Burkholderia sp. strain DNT has been reported previously. We report here the isolation of additional strains with the ability to mineralize 2,4-DNT by the same pathway and the isolation and characterization of bacterial strains that mineralize 2,6-dinitrotoluene (2,6-DNT) by a different pathway. Burkholderia cepacia strain JS850 and Hydrogenophaga palleronii strain JS863 grew on 2,6-DNT as the sole source of carbon...

  18. Degradation of streptomycin in aquatic environment: kinetics, pathway, and antibacterial activity analysis.

    Science.gov (United States)

    Shen, Yanru; Zhao, Wenyan; Zhang, Chunling; Shan, Yujie; Shi, Junxian

    2017-06-01

    Streptomycin used in human and veterinary medicine is released into the environment mainly through excretions. As such, its elimination in water should be investigated to control pollution. In this study, the degradation of streptomycin in water was studied, and the influence of variables, including light exposure, solution pH, temperature, ionic strength, dissolved organic matter (DOM), and coexisting surfactants, on degradation was investigated. Streptomycin degradation was consistent with the first-order model in aquatic environments. Its degradation rate under light exposure was 2.6-fold faster than that in the dark. Streptomycin was stable under neutral conditions, but it was easily decomposed in acidic and basic environments. Streptomycin degradation was enhanced by high temperature, and its half-life decreased from 103.4 days at 15 °C to 30.9 days at 40 °C. This process was also accelerated by the presence of Ca(2+) and slightly improved by the addition of HA. Streptomycin degradation was suppressed by high levels of the cationic surfactant cetyltri- methylammonium bromide (CTAB), but was promoted by the anionic surfactant sodium dodecyl benzene sulfonate (SDBS). The main degradation intermediates/products were identified through liquid chromatography-mass spectrometry, and the possible degradation pathway was proposed. The antibacterial activity of streptomycin solution was also determined during degradation. Results showed that STR degradation generated intermediates/products with weaker antibacterial activity than the parent compound.

  19. Unveiling New Degradation Intermediates/Pathways from the Photocatalytic Degradation of Microcystin-LR

    Science.gov (United States)

    This study focuses on the identification of reaction intermediates formed during the photocatalytic degradation of the cyanotoxin microcystin-LR with immobilized TiO2 Tphotocatalysts at neutral pH. To differentiate between impurities already existing in the MC-LR stand...

  20. Rapid reversal of translational silencing: Emerging role of microRNA degradation pathways in neuronal plasticity.

    Science.gov (United States)

    Fu, Xiuping; Shah, Aparna; Baraban, Jay M

    2016-09-01

    As microRNAs silence translation, rapid reversal of this process has emerged as an attractive mechanism for driving de novo protein synthesis mediating neuronal plasticity. Herein, we summarize recent studies identifying neuronal stimuli that trigger rapid decreases in microRNA levels and reverse translational silencing of plasticity transcripts. Although these findings indicate that neuronal stimulation elicits rapid degradation of selected microRNAs, we are only beginning to decipher the molecular pathways involved. Accordingly, we present an overview of several molecular pathways implicated in mediating microRNA degradation: Lin-28, translin/trax, and MCPIP1. As these degradation pathways target distinct subsets of microRNAs, they enable neurons to reverse silencing rapidly, yet selectively. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Elucidation of pathways of ribosomal RNA degradation: an essential role for RNase E

    Science.gov (United States)

    Sulthana, Shaheen; Basturea, Georgeta N.; Deutscher, Murray P.

    2016-01-01

    Although normally stable in growing cells, ribosomal RNAs are degraded under conditions of stress, such as starvation, and in response to misassembled or otherwise defective ribosomes in a process termed RNA quality control. Previously, our laboratory found that large fragments of 16S and 23S rRNA accumulate in strains lacking the processive exoribonucleases RNase II, RNase R, and PNPase, implicating these enzymes in the later steps of rRNA breakdown. Here, we define the pathways of rRNA degradation in the quality control process and during starvation, and show that the essential endoribonuclease, RNase E, is required to make the initial cleavages in both degradative processes. We also present evidence that explains why the exoribonuclease, RNase PH, is required to initiate the degradation of rRNA during starvation. The data presented here provide the first detailed description of rRNA degradation in bacterial cells. PMID:27298395

  2. Identification and characterization of process-related substances and degradation products in apremilast: Process optimization and degradation pathway elucidation.

    Science.gov (United States)

    Lu, Yuting; Shen, Xiaoyue; Hang, Taijun; Song, Min

    2017-07-15

    This study aims at investigating the separation, identification and characterization of related substances in apremilast by LC-MS hyphenated techniques, as well as the synthesis optimization and the degradation pathways elucidation. Forced degradation studies were conducted under the ICH prescribed stress conditions. The chromatographic separation was achieved on XBridge C18 column (4.6mm×150mm, 3.5μm) using a mobile phase consisting of water adjusted to pH 3.0 with formic acid as solvent A and acetonitrile as solvent B in linear gradient elution program. Twelve related substances were detected all together in apremilast and its stress samples. Their structures were identified mainly through positive ESI high-resolution TOF-MS analysis of the parent ions' accurate masses and elemental compositions, and the corresponding MS/MS spectra elucidation. There were three process-related substances and nine degradation products, seven of them were first reported. Two degradation products and one process-related substance were further verified by semi-preparation and NMR determination. Their origins and formation mechanisms were also discussed, based on which effective approaches for the synthesis optimization were conducted. Therefore, the related substances investigation are valuable for apremilast manufacturing process optimization and quality control. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Terrestrial and marine perspectives on modeling organic matter degradation pathways.

    Science.gov (United States)

    Burd, Adrian B; Frey, Serita; Cabre, Anna; Ito, Takamitsu; Levine, Naomi M; Lønborg, Christian; Long, Matthew; Mauritz, Marguerite; Thomas, R Quinn; Stephens, Brandon M; Vanwalleghem, Tom; Zeng, Ning

    2016-01-01

    Organic matter (OM) plays a major role in both terrestrial and oceanic biogeochemical cycles. The amount of carbon stored in these systems is far greater than that of carbon dioxide (CO2 ) in the atmosphere, and annual fluxes of CO2 from these pools to the atmosphere exceed those from fossil fuel combustion. Understanding the processes that determine the fate of detrital material is important for predicting the effects that climate change will have on feedbacks to the global carbon cycle. However, Earth System Models (ESMs) typically utilize very simple formulations of processes affecting the mineralization and storage of detrital OM. Recent changes in our view of the nature of this material and the factors controlling its transformation have yet to find their way into models. In this review, we highlight the current understanding of the role and cycling of detrital OM in terrestrial and marine systems and examine how this pool of material is represented in ESMs. We include a discussion of the different mineralization pathways available as organic matter moves from soils, through inland waters to coastal systems and ultimately into open ocean environments. We argue that there is strong commonality between aspects of OM transformation in both terrestrial and marine systems and that our respective scientific communities would benefit from closer collaboration.

  4. Degradation pathway of malachite green in a novel dual-tank photoelectrochemical catalytic reactor.

    Science.gov (United States)

    Diao, Zenghui; Li, Mingyu; Zeng, Fanyin; Song, Lin; Qiu, Rongliang

    2013-09-15

    A novel dual-tank photoelectrochemical catalytic reactor was designed to investigate the degradation pathway of malachite green. A thermally formed TiO₂/Ti thin film electrode was used as photoanode, graphite was used as cathode, and a saturated calomel electrode was employed as the reference electrode in the reactor. In the reactor, the anode and cathode tanks were connected by a cation exchange membrane. Results showed that the decolorization ratio of malachite green in the anode and cathode was 98.5 and 96.5% after 120 min, respectively. Malachite green in the two anode and cathode tanks was oxidized, achieving the bipolar double effect. Malachite green in both the anode and cathode tanks exhibited similar catalytic degradation pathways. The double bond of the malachite green molecule was attacked by strong oxidative hydroxyl radicals, after which the organic compound was degraded by the two pathways into 4,4-bis(dimethylamino) benzophenone, 4-(dimethylamino) benzophenone, 4-(dimethylamino) phenol, and other intermediate products. Eventually, malachite green was degraded into oxalic acid as a small molecular organic acid, which was degraded by processes such as demethylation, deamination, nitration, substitution, addition, and other reactions. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. Degradation of oxcarbazepine by UV-activated persulfate oxidation: kinetics, mechanisms, and pathways.

    Science.gov (United States)

    Bu, Lingjun; Zhou, Shiqing; Shi, Zhou; Deng, Lin; Li, Guangchao; Yi, Qihang; Gao, Naiyun

    2016-02-01

    The degradation kinetics and mechanism of the antiepileptic drug oxcarbazepine (OXC) by UV-activated persulfate oxidation were investigated in this study. Results showed that UV/persulfate (UV/PS) process appeared to be more effective in degrading OXC than UV or PS alone. The OXC degradation exhibited a pseudo-first order kinetics pattern and the degradation rate constants (k obs) were affected by initial OXC concentration, PS dosage, initial pH, and humic acid concentration to different degrees. It was found that low initial OXC concentration, high persulfate dosage, and initial pH enhanced the OXC degradation. Additionally, the presence of humic acid in the solution could greatly inhibit the degradation of OXC. Moreover, hydroxyl radical (OH•) and sulfate radical (SO4 (-)••) were identified to be responsible for OXC degradation and SO4 (-)• made the predominant contribution in this study. Finally, major intermediate products were identified and a preliminary degradation pathway was proposed. Results demonstrated that UV/PS system is a potential technology to control the water pollution caused by emerging contaminants such as OXC.

  6. A second pathway to degrade pyrimidine nucleic acid precursors in eukaryotes

    DEFF Research Database (Denmark)

    Andersen, Gorm; Bjornberg, Olof; Polakova, Silvia;

    2008-01-01

    Pyrimidine bases are the central precursors for RNA and DNA, and their intracellular pools are determined by de novo, salvage and catabolic pathways. In eukaryotes, degradation of uracil has been believed to proceed only via the reduction to dihydrouracil. Using a yeast model, Saccharomyces kluyv...

  7. Kinetic models and pathways of ronidazole degradation by chlorination, UV irradiation and UV/chlorine processes.

    Science.gov (United States)

    Qin, Lang; Lin, Yi-Li; Xu, Bin; Hu, Chen-Yan; Tian, Fu-Xiang; Zhang, Tian-Yang; Zhu, Wen-Qian; Huang, He; Gao, Nai-Yun

    2014-11-15

    Degradation kinetics and pathways of ronidazole (RNZ) by chlorination (Cl2), UV irradiation and combined UV/chlorine processes were investigated in this paper. The degradation kinetics of RNZ chlorination followed a second-order behavior with the rate constants calculated as (2.13 ± 0.15) × 10(2) M(-2) s(-1), (0.82 ± 0.52) × 10(-2) M(-1) s(-1) and (2.06 ± 0.09) × 10(-1) M(-1) s(-1) for the acid-catalyzed reaction, as well as the reactions of RNZ with HOCl and OCl(-), respectively. Although UV irradiation degraded RNZ more effectively than chlorination did, very low quantum yield of RNZ at 254 nm was obtained as 1.02 × 10(-3) mol E(-1). RNZ could be efficiently degraded and mineralized in the UV/chlorine process due to the generation of hydroxyl radicals. The second-order rate constant between RNZ and hydroxyl radical was determined as (2.92 ± 0.05) × 10(9) M(-1) s(-1). The degradation intermediates of RNZ during the three processes were identified with Ultra Performance Liquid Chromatography - Electrospray Ionization - mass spectrometry and the degradation pathways were then proposed. Moreover, the variation of chloropicrin (TCNM) and chloroform (CF) formation after the three processes were further evaluated. Enhanced formation of CF and TCNM precursors during UV/chlorine process deserves extensive attention in drinking water treatment.

  8. Modelling pathways to Rubisco degradation: a structural equation network modelling approach.

    Directory of Open Access Journals (Sweden)

    Catherine Tétard-Jones

    Full Text Available 'Omics analysis (transcriptomics, proteomics quantifies changes in gene/protein expression, providing a snapshot of changes in biochemical pathways over time. Although tools such as modelling that are needed to investigate the relationships between genes/proteins already exist, they are rarely utilised. We consider the potential for using Structural Equation Modelling to investigate protein-protein interactions in a proposed Rubisco protein degradation pathway using previously published data from 2D electrophoresis and mass spectrometry proteome analysis. These informed the development of a prior model that hypothesised a pathway of Rubisco Large Subunit and Small Subunit degradation, producing both primary and secondary degradation products. While some of the putative pathways were confirmed by the modelling approach, the model also demonstrated features that had not been originally hypothesised. We used Bayesian analysis based on Markov Chain Monte Carlo simulation to generate output statistics suggesting that the model had replicated the variation in the observed data due to protein-protein interactions. This study represents an early step in the development of approaches that seek to enable the full utilisation of information regarding the dynamics of biochemical pathways contained within proteomics data. As these approaches gain attention, they will guide the design and conduct of experiments that enable 'Omics modelling to become a common place practice within molecular biology.

  9. New hydrocarbon degradation pathways in the microbial metagenome from Brazilian petroleum reservoirs.

    Directory of Open Access Journals (Sweden)

    Isabel Natalia Sierra-García

    Full Text Available Current knowledge of the microbial diversity and metabolic pathways involved in hydrocarbon degradation in petroleum reservoirs is still limited, mostly due to the difficulty in recovering the complex community from such an extreme environment. Metagenomics is a valuable tool to investigate the genetic and functional diversity of previously uncultured microorganisms in natural environments. Using a function-driven metagenomic approach, we investigated the metabolic abilities of microbial communities in oil reservoirs. Here, we describe novel functional metabolic pathways involved in the biodegradation of aromatic compounds in a metagenomic library obtained from an oil reservoir. Although many of the deduced proteins shared homology with known enzymes of different well-described aerobic and anaerobic catabolic pathways, the metagenomic fragments did not contain the complete clusters known to be involved in hydrocarbon degradation. Instead, the metagenomic fragments comprised genes belonging to different pathways, showing novel gene arrangements. These results reinforce the potential of the metagenomic approach for the identification and elucidation of new genes and pathways in poorly studied environments and contribute to a broader perspective on the hydrocarbon degradation processes in petroleum reservoirs.

  10. New Hydrocarbon Degradation Pathways in the Microbial Metagenome from Brazilian Petroleum Reservoirs

    Science.gov (United States)

    Sierra-García, Isabel Natalia; Correa Alvarez, Javier; Pantaroto de Vasconcellos, Suzan; Pereira de Souza, Anete; dos Santos Neto, Eugenio Vaz; de Oliveira, Valéria Maia

    2014-01-01

    Current knowledge of the microbial diversity and metabolic pathways involved in hydrocarbon degradation in petroleum reservoirs is still limited, mostly due to the difficulty in recovering the complex community from such an extreme environment. Metagenomics is a valuable tool to investigate the genetic and functional diversity of previously uncultured microorganisms in natural environments. Using a function-driven metagenomic approach, we investigated the metabolic abilities of microbial communities in oil reservoirs. Here, we describe novel functional metabolic pathways involved in the biodegradation of aromatic compounds in a metagenomic library obtained from an oil reservoir. Although many of the deduced proteins shared homology with known enzymes of different well-described aerobic and anaerobic catabolic pathways, the metagenomic fragments did not contain the complete clusters known to be involved in hydrocarbon degradation. Instead, the metagenomic fragments comprised genes belonging to different pathways, showing novel gene arrangements. These results reinforce the potential of the metagenomic approach for the identification and elucidation of new genes and pathways in poorly studied environments and contribute to a broader perspective on the hydrocarbon degradation processes in petroleum reservoirs. PMID:24587220

  11. Tissue factor pathway inhibitor relates to fibrin degradation in patients with acute deep venous thrombosis

    DEFF Research Database (Denmark)

    Sidelmann, Johannes J; Bladbjerg, Else-Marie; Gram, Jørgen

    2008-01-01

    Reduced concentration of tissue factor pathway inhibitor is a risk factor for development of deep venous thrombosis, whereas elevated concentrations of tissue factor pathway inhibitor are observed in patients with acute myocardial infarction and disseminated intravascular coagulation. Presently, we...... studied the association between inflammation, endothelial cell perturbation, fibrin degradation and the concentration of tissue factor pathway inhibitor in patients suspected for acute deep venous thrombosis. We determined the tissue factor pathway inhibitor -33T/C polymorphism, free and total tissue...... factor pathway inhibitor, C-reactive protein, von Willebrand factor and D-Dimer in 160 consecutive patients admitted to hospital with a tentative diagnosis of acute deep venous thrombosis. Deep venous thrombosis was identified in 57 patients (18 distal and 39 proximal). The distribution of the tissue...

  12. Bacterial community structure and predicted alginate metabolic pathway in an alginate-degrading bacterial consortium.

    Science.gov (United States)

    Kita, Akihisa; Miura, Toyokazu; Kawata, Satoshi; Yamaguchi, Takeshi; Okamura, Yoshiko; Aki, Tsunehiro; Matsumura, Yukihiko; Tajima, Takahisa; Kato, Junichi; Nishio, Naomichi; Nakashimada, Yutaka

    2016-03-01

    Methane fermentation is one of the effective approaches for utilization of brown algae; however, this process is limited by the microbial capability to degrade alginate, a main polysaccharide found in these algae. Despite its potential, little is known about anaerobic microbial degradation of alginate. Here we constructed a bacterial consortium able to anaerobically degrade alginate. Taxonomic classification of 16S rRNA gene, based on high-throughput sequencing data, revealed that this consortium included two dominant strains, designated HUA-1 and HUA-2; these strains were related to Clostridiaceae bacterium SK082 (99%) and Dysgonomonas capnocytophagoides (95%), respectively. Alginate lyase activity and metagenomic analyses, based on high-throughput sequencing data, revealed that this bacterial consortium possessed putative genes related to a predicted alginate metabolic pathway. However, HUA-1 and 2 did not grow on agar medium with alginate by using roll-tube method, suggesting the existence of bacterial interactions like symbiosis for anaerobic alginate degradation.

  13. Degradation kinetics and pathway of phenol by Pseudomonas and Bacillus species.

    Science.gov (United States)

    Hasan, Syed Adnan; Jabeen, Suraiya

    2015-01-02

    This article elucidates that strain Pseudomonas aeruginosa (IES-Ps-1) is a versatile toxic organic compound degrader. With the degradation of malathion and cypermethrin (studied by other researchers previously), this strain was able to degrade phenol. Two other indigenous soil flora (i.e., Pseudomonas sp. (IES-S) and Bacillus subtilis (IES-B)) were also found to be potential phenol degraders. Phenol was degraded with Monod kinetics during growth in nutrient broth and mineral salts medium. Before entering into the growth inhibition phase, strains IES-Ps-1, IES-S and IES-B could tolerate up to 400, 700 and 500 mg/L phenol, respectively, when contained in nutrient broth. However, according to the Luong-Levenspiel model, the growth of strains IES-Ps-1, IES-S and IES-B would cease at 2000, 2174 and 2190 mg/L phenol, respectively. Strain IES-Ps-1 degraded 700, 900 and 1050 mg/L phenol contained in mineral salts medium with the specific rates of 0.034, 0.075 and 0.021 h(-1), respectively. All these strains grew by making clusters when exposed to phenol in order to prevent damages due to high substrate concentration. These strains transformed phenol into catechol, which was then degraded via ortho-cleavage pathway.

  14. Nuclear mRNA degradation pathway(s are implicated in Xist regulation and X chromosome inactivation.

    Directory of Open Access Journals (Sweden)

    Constance Ciaudo

    2006-06-01

    Full Text Available A critical step in X-chromosome inactivation (XCI, which results in the dosage compensation of X-linked gene expression in mammals, is the coating of the presumptive inactive X chromosome by the large noncoding Xist RNA, which then leads to the recruitment of other factors essential for the heterochromatinisation of the inactive X and its transcriptional silencing. In an approach aimed at identifying genes implicated in the X-inactivation process by comparative transcriptional profiling of female and male mouse gastrula, we identified the Eif1 gene involved in translation initiation and RNA degradation. We show here that female embryonic stem cell lines, silenced by RNA interference for the Eif1 gene, are unable to form Xist RNA domains upon differentiation and fail to undergo X-inactivation. To probe further an effect involving RNA degradation pathways, the inhibition by RNA interference of Rent1, a factor essential for nonsense-mediated decay and Exosc10, a specific nuclear component of the exosome, was analysed and shown to similarly impair Xist upregulation and XCI. In Eif1-, Rent1-, and Exosc10-interfered clones, Xist spliced form(s are strongly downregulated, while the levels of unspliced form(s of Xist and the stability of Xist RNA remain comparable to that of the control cell lines. Our data suggests a role for mRNA nuclear degradation pathways in the critical regulation of spliced Xist mRNA levels and the onset of the X-inactivation process.

  15. Metagenomic identification of bacterioplankton taxa and pathways involved in microcystin degradation in lake erie.

    Directory of Open Access Journals (Sweden)

    Xiaozhen Mou

    Full Text Available Cyanobacterial harmful blooms (CyanoHABs that produce microcystins are appearing in an increasing number of freshwater ecosystems worldwide, damaging quality of water for use by human and aquatic life. Heterotrophic bacteria assemblages are thought to be important in transforming and detoxifying microcystins in natural environments. However, little is known about their taxonomic composition or pathways involved in the process. To address this knowledge gap, we compared the metagenomes of Lake Erie free-living bacterioplankton assemblages in laboratory microcosms amended with microcystins relative to unamended controls. A diverse array of bacterial phyla were responsive to elevated supply of microcystins, including Acidobacteria, Actinobacteria, Bacteroidetes, Planctomycetes, Proteobacteria of the alpha, beta, gamma, delta and epsilon subdivisions and Verrucomicrobia. At more detailed taxonomic levels, Methylophilales (mainly in genus Methylotenera and Burkholderiales (mainly in genera Bordetella, Burkholderia, Cupriavidus, Polaromonas, Ralstonia, Polynucleobacter and Variovorax of Betaproteobacteria were suggested to be more important in microcystin degradation than Sphingomonadales of Alphaproteobacteria. The latter taxa were previously thought to be major microcystin degraders. Homologs to known microcystin-degrading genes (mlr were not overrepresented in microcystin-amended metagenomes, indicating that Lake Erie bacterioplankton might employ alternative genes and/or pathways in microcystin degradation. Genes for xenobiotic metabolism were overrepresented in microcystin-amended microcosms, suggesting they are important in bacterial degradation of microcystin, a phenomenon that has been identified previously only in eukaryotic systems.

  16. Degradation kinetics and pathways of three calcium channel blockers under UV irradiation.

    Science.gov (United States)

    Zhu, Bing; Zonja, Bozo; Gonzalez, Oscar; Sans, Carme; Pérez, Sandra; Barceló, Damia; Esplugas, Santiago; Xu, Ke; Qiang, Zhimin

    2015-12-01

    Calcium channel blockers (CCBs) are a group of pharmaceuticals widely prescribed to lower blood pressure and treat heart diseases. They have been frequently detected in wastewater treatment plant (WWTP) effluents and downstream river waters, thus inducing a potential risk to aquatic ecosystems. However, little is known about the behavior and fate of CCBs under UV irradiation, which has been adopted as a primary disinfection method for WWTP effluents. This study investigated the degradation kinetics and pathways of three commonly-used CCBs, including amlodipine (AML), diltiazem (DIL), and verapamil (VER), under UV (254 nm) irradiation. The chemical structures of transformation byproducts (TBPs) were first identified to assess the potential ecological hazards. On that basis, a generic solid-phase extraction method, which simultaneously used four different cartridges, was adopted to extract and enrich the TBPs. Thereafter, the photo-degradation of target CCBs was performed under UV fluences typical for WWTP effluent disinfection. The degradation of all three CCBs conformed to the pseudo-first-order kinetics, with rate constants of 0.031, 0.044 and 0.011 min(-1) for AML, DIL and VER, respectively. By comparing the MS(2) fragments and the evolution (i.e., formation or decay) trends of identified TBPs, the degradation pathways were proposed. In the WWTP effluent, although the target CCBs could be degraded, several TBPs still contained the functional pharmacophores and reached peak concentrations under UV fluences of 40-100 mJ cm(-2).

  17. Metagenomic identification of bacterioplankton taxa and pathways involved in microcystin degradation in lake erie.

    Science.gov (United States)

    Mou, Xiaozhen; Lu, Xinxin; Jacob, Jisha; Sun, Shulei; Heath, Robert

    2013-01-01

    Cyanobacterial harmful blooms (CyanoHABs) that produce microcystins are appearing in an increasing number of freshwater ecosystems worldwide, damaging quality of water for use by human and aquatic life. Heterotrophic bacteria assemblages are thought to be important in transforming and detoxifying microcystins in natural environments. However, little is known about their taxonomic composition or pathways involved in the process. To address this knowledge gap, we compared the metagenomes of Lake Erie free-living bacterioplankton assemblages in laboratory microcosms amended with microcystins relative to unamended controls. A diverse array of bacterial phyla were responsive to elevated supply of microcystins, including Acidobacteria, Actinobacteria, Bacteroidetes, Planctomycetes, Proteobacteria of the alpha, beta, gamma, delta and epsilon subdivisions and Verrucomicrobia. At more detailed taxonomic levels, Methylophilales (mainly in genus Methylotenera) and Burkholderiales (mainly in genera Bordetella, Burkholderia, Cupriavidus, Polaromonas, Ralstonia, Polynucleobacter and Variovorax) of Betaproteobacteria were suggested to be more important in microcystin degradation than Sphingomonadales of Alphaproteobacteria. The latter taxa were previously thought to be major microcystin degraders. Homologs to known microcystin-degrading genes (mlr) were not overrepresented in microcystin-amended metagenomes, indicating that Lake Erie bacterioplankton might employ alternative genes and/or pathways in microcystin degradation. Genes for xenobiotic metabolism were overrepresented in microcystin-amended microcosms, suggesting they are important in bacterial degradation of microcystin, a phenomenon that has been identified previously only in eukaryotic systems.

  18. Kinetics and pathways of cyanide degradation at high temperatures and pressures.

    Science.gov (United States)

    Oulego, Paula; Laca, Adriana; Diaz, Mario

    2013-02-05

    The degradation of cyanide was performed in a 1-L semibatch reactor at temperatures between 393 and 473 K and at total pressures in the range of 2.0-8.0 MPa. The initial pH of the solution was set at 11, whereas initial concentrations ranged from 3.85 to 25 mM, which resemble the typical concentrations of cyanide-containing wastewater. The change with time of cyanide concentration, intermediates, and final products was analyzed in order to elucidate the reaction pathways. The experimental results suggest two parallel pathways of alkaline hydrolysis for the degradation of the pollutant. Formate and ammonia were identified as the final reaction products for one of the pathways, whereas carbon dioxide, nitrogen, and hydrogen were considered to be the final products for the other one. The degradation reaction results were fitted to first-order kinetic equations with respect to cyanide, giving respectively activation energies of 108.2 ± 3.3 and 77.6 ± 3.0 kJ/mol. Consequently, the formation of formate and ammonia is favored at high temperatures, whereas low temperatures favored the pathway leading to the formation of carbon dioxide and nitrogen.

  19. NIR is degraded by the anaphase-promoting complex proteasome pathway

    Directory of Open Access Journals (Sweden)

    Jeong Ho Myong

    2014-01-01

    Full Text Available Novel INHAT Repressor (NIR is a histone acetylation inhibitor that can directly bind histone complexes and the tumor suppressors p53 and p63. Because NIR is mainly localized in the nucleolus and disappears from the nucleolus upon RNase treatment, it is thought to bind RNA or ribonucleoproteins. When NIR moves to the cytoplasm, it is immediately degraded; this degradation was blocked by MG132, a proteasome inhibitor. Furthermore, the central domain of NIR specifically bound APC-CCdh1. These data show that the stability of NIR is governed by the ubiquitin/proteasome pathway.

  20. [Degradation of L-phenylalanine and of aromatic carboxylic acids by chloridazon-degrading bacteria. Combination of side chain degradation and dioxygenase pathway].

    Science.gov (United States)

    Wegst, W; Lingens, F

    1981-09-01

    Strain N of Chloridazon-degrading bacteria degrades phenylalanine via cis-2,3-dihydro-2,3-dihydroxyphenylalanine,2,3-dihydroxyphenylalanine aspartate and 4-hydroxy-2-oxovalerate [Hoppe-Seyler's Z. Physiol. Chem. 360, 957--969, (1979); Biochem. J. 194, 679--684 (1981)]. cis-2,3-Dihydro-2,3-dihydroxyphenylalanine and 2,3-dihydroxyphenylalanine as well as phenylpyruvate, cis-2,3-dihydro-2,3-dihydroxyphenylpyruvate, 2,3-dihydroxyphenylpyruvate, cis-2,3-dihydro-2,3-dihydroxyphenylacetate, 2,3-dihydroxyphenylacetate and 2,3-dihydroxybenzaldehyde are detectable in the medium of strain E during growth on phenylalanine. Incubation with phenylacetate, 3-phenylpropionate or 4-phenylbutyrate leads to the accumulation of the corresponding cis-2,3-dihydro-2,3-dihydroxyphenyl derivatives. These compounds are transformed with dihydrodiol dehydrogenase to 2,3-dihydroxyphenylacetate, 3-(2,3-dihydroxyphenyl)propionate and 4-(2,3-dihydroxyphenyl)-butyrate, 3-(2,3-dihydroxyphenyl)propionate is attacked by a catechol 2,3-dioxygenase and the meta-cleavage product is again cleaved by a hydrolase yielding succinate. In a similar reaction sequence the degradation of 4-phenylbutyrate leads to the formation of glutarate. From the growth medium of strain E on phenylacetate also small amounts of 2-, 3- and 4-hydroxyphenylacetate were isolated. Resting cells were shown to metabolize 3- and 4-hydroxyphenylacetate via homogentisate and 3,4-dihydroxyphenylacetate. In the culture medium of strain K2AP benzoate could be detected. Pathways for the degradation of phenylalanine and aromatic carboxylic acids in chloridazon degrading bacteria are proposed.

  1. Degradation of 4-nitrocatechol by Burkholderia cepacia: a plasmid-encoded novel pathway.

    Science.gov (United States)

    Chauhan, A; Samanta, S K; Jain, R K

    2000-05-01

    Pseudomonas cepacia RKJ200 (now described as Burkholderia cepacia) has been shown to utilize p-nitrophenol (PNP) as sole carbon and energy source. The present work demonstrates that RKJ200 utilizes 4-nitrocatechol (NC) as the sole source of carbon, nitrogen and energy, and is degraded with concomitant release of nitrite ions. Several lines of evidence, including thin layer chromatography, gas chromatography, 1H-nuclear magnetic resonance, gas chromatography-mass spectrometry, spectral analyses and quantification of intermediates by high performance liquid chromatography, have shown that NC is degraded via 1,2, 4-benzenetriol (BT) and hydroquinone (HQ) formation. Studies carried out on a PNP- derivative and a PNP+ transconjugant also demonstrate that the genes for the NC degradative pathway reside on the plasmid present in RKJ200; the same plasmid had earlier been shown to encode genes for PNP degradation, which is also degraded via HQ formation. It is likely, therefore, that the same sets of genes encode the further metabolism of HQ in NC and PNP degradation.

  2. New metabolic pathway for degradation of 2-nitrobenzoate by Arthrobacter sp. SPG

    Directory of Open Access Journals (Sweden)

    Pankaj Kumar Arora

    2015-06-01

    Full Text Available Arthrobacter sp. SPG utilized 2-nitrobenzoate as its sole source of carbon and energy and degraded it with accumulation of stoichiometric amounts of nitrite ions. Salicylate and catechol were detected as metabolites of the 2-nitrobenzoate degradation using high performance liquid chromatography and gas chromatography-mass spectrometry. Enzyme activities for 2-nitrobenzoate-2-monooxygenase, salicylate hydroxylase, and catechol-1,2-dioxygenase were detected in the crude extracts of the 2-nitrobenzoate-induced cells of strain SPG. The 2-nitrobenzoate-monooxygenase activity resulted in formation of salicylate and nitrite from 2-nitrobenzoate whereas salicylate hydroxylase catalyzed the conversion of salicylate to catechol. The ring-cleaving enzyme, catechol-1,2-dioxygenase cleaved catechol to cis, cis-muconic acid. Cells of strain SPG were able to degrade 2-nitrobenzoate in sterile as well as non-sterile soil microcosms. The results of microcosm studies showed that strain SPG degraded more than 90% of 2-nitrobenzoate within 10-12 days. This study clearly shows that Arthrobacter sp. SPG degraded 2-nitrobenzoate via a new pathway with formation of salicylate and catechol as metabolites. Arthrobacter sp. SPG may be used for bioremediation of 2-nitrobenzoate-contaminated sites due to its ability to degrade 2-nitrobenzoate in soil.

  3. New metabolic pathway for degradation of 2-nitrobenzoate by Arthrobacter sp. SPG

    Science.gov (United States)

    Arora, Pankaj K.; Sharma, Ashutosh

    2015-01-01

    Arthrobacter sp. SPG utilized 2-nitrobenzoate as its sole source of carbon and energy and degraded it with accumulation of stoichiometric amounts of nitrite ions. Salicylate and catechol were detected as metabolites of the 2-nitrobenzoate degradation using high performance liquid chromatography and gas chromatography–mass spectrometry. Enzyme activities for 2-nitrobenzoate-2-monooxygenase, salicylate hydroxylase, and catechol-1,2-dioxygenase were detected in the crude extracts of the 2-nitrobenzoate-induced cells of strain SPG. The 2-nitrobenzoate-monooxygenase activity resulted in formation of salicylate and nitrite from 2-nitrobenzoate, whereas salicylate hydroxylase catalyzed the conversion of salicylate to catechol. The ring-cleaving enzyme, catechol-1,2-dioxygenase cleaved catechol to cis,cis-muconic acid. Cells of strain SPG were able to degrade 2-nitrobenzoate in sterile as well as non-sterile soil microcosms. The results of microcosm studies showed that strain SPG degraded more than 90% of 2-nitrobenzoate within 10–12 days. This study clearly shows that Arthrobacter sp. SPG degraded 2-nitrobenzoate via a new pathway with formation of salicylate and catechol as metabolites. Arthrobacter sp. SPG may be used for bioremediation of 2-nitrobenzoate-contaminated sites due to its ability to degrade 2-nitrobenzoate in soil. PMID:26082768

  4. 4-Phenylbutyric acid reduces mutant-TGFBIp levels and ER stress through activation of ERAD pathway in corneal fibroblasts of granular corneal dystrophy type 2.

    Science.gov (United States)

    Choi, Seung-Il; Lee, Eunhee; Jeong, Jang Bin; Akuzum, Begum; Maeng, Yong-Sun; Kim, Tae-Im; Kim, Eung Kweon

    2016-09-02

    Granular corneal dystrophy type 2 (GCD2) is caused by a point mutation (R124H) in the transforming growth factor β-induced (TGFBI) gene. In GCD2 corneal fibroblasts, secretion of the accumulated mutant TGFBI-encoded protein (TGFBIp) is delayed via the endoplasmic reticulum (ER)/Golgi-dependent secretory pathway. However, ER stress as the pathogenic mechanism underlying GCD2 has not been fully characterized. The aim of this study was to confirm whether ER stress is linked to GCD2 pathogenesis and whether the chemical chaperone, 4-phenylbutyric acid (4-PBA), could be exploited as a therapy for GCD2. We found that the ER chaperone binding immunoglobulin protein (BiP) and the protein disulfide isomerase (PDI) were elevated in GCD2. Western bolt analysis also showed a significant increase in both the protein levels and the phosphorylation of the key ER stress kinases, inositol-requiring enzyme 1α (IRE1α) and double stranded RNA activated protein kinase (PKR)-like ER kinase, as well as in levels of their downstream targets, X box-binding protein 1 (XBP1) and activating transcription factor 4, respectively, in GCD2 corneal fibroblasts. GCD2 cells were found to be more susceptible to ER stress-induced cell death than were wild-type corneal fibroblasts. Treatment with 4-PBA considerably reduced the levels of BiP, IRE1α, and XBP1 in GCD2 cells; notably, 4-PBA treatment significantly reduced the levels of TGFBIp without change in TGFBI mRNA levels. In addition, TGFBIp levels were significantly reduced under ER stress and this reduction was considerably suppressed by the ubiquitin proteasome inhibitor MG132, indicating TGFBIp degradation via the ER-associated degradation pathway. Treatment with 4-PBA not only protected against the GCD2 cell death induced by ER stress but also significantly suppressed the MG132-mediated increase in TGFBIp levels under ER stress. Together, these results suggest that ER stress might comprise an important factor in GCD2 pathophysiology and

  5. Novel degradation pathway and kinetic analysis for buprofezin removal by newly isolated Bacillus sp.

    Science.gov (United States)

    Wang, Guangli; Xu, Dayong; Xiong, Minghua; Zhang, Hui; Li, Feng; Liu, Yuan

    2016-09-15

    Given the intensive and widespread application of the pesticide, buprofezin, its environmental residues potentially pose a problem; yet little is known about buprofezin's kinetic and metabolic behaviors. In this study, a novel gram-positive strain, designated BF-5, isolated from aerobic activated sludge, was found to be capable of metabolizing buprofezin as its sole energy, carbon, and nitrogen source. Based on its physiological and biochemical characteristics, other aspects of its phenotype, and a phylogenetic analysis, strain BF-5 was identified as Bacillus sp. This study investigated the effect of culture conditions on bacterial growth and substrate degradation, such as pH, temperature, initial concentration, different nitrogen source, and additional nitrogen sources as co-substrates. The degradation rate parameters, qmax, Ks, Ki and Sm were determined to be 0.6918 h(-1), 105.4 mg L(-1), 210.5 mg L(-1), and 148.95 mg L(-1) respectively. The capture of unpublished potential metabolites by gas chromatography-mass spectrometry (GC-MS) analysis has led to the proposal of a novel degradation pathway. Taken together, our results clarify buprofezin's biodegradation pathway(s) and highlight the promising potential of strain BF-5 in bioremediation of buprofezin-contaminated environments. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Thermally induced degradation pathways of three different antibody-based drug development candidates.

    Science.gov (United States)

    Fincke, Anja; Winter, Jonas; Bunte, Thomas; Olbrich, Carsten

    2014-10-01

    Protein-based medicinal products are prone to undergo a variety of chemical and physical degradation pathways. One of the most important exogenous stress condition to consider during manufacturing, transport and storage processes is temperature, because antibody-based therapeutics are only stable in a limited temperature range. In this study, three different formats of antibody-based molecules (IgG1, a bispecific scFv and a fab fragment) were exposed to thermal stress conditions occurring during transport and storage. For evaluation, an analytical platform was developed for the detection and characterization of relevant degradation pathways of different antibody-based therapeutics. The effect of thermal stress conditions on the stability of the three antibody-based formats was therefore investigated using visual inspection, different spectroscopic measurements, dynamic light scattering (DLS), differential scanning calorimetry (DSC), electrophoresis, asymmetric flow field-flow fractionation (AF4) and surface plasmon resonance technology (SPR). In summary, thermal stress led to heterogeneous chemical and physical degradation pathways of all three antibody-based formats used. In addition, identical exogenous stress conditions resulted in different kinds and levels of aggregates and fragmentation products. This knowledge is fundamental for a systematic and successful stabilization of protein-based therapeutics by the use of formulation additives.

  7. Activity, biomass and composition of microbial communities and their degradation pathways in exposed propazine soil.

    Science.gov (United States)

    Jiang, Chen; Lu, Yi Chen; Xu, Jiang Yan; Song, Yang; Song, Yue; Zhang, Shu Hao; Ma, Li Ya; Lu, Feng Fan; Wang, Ya Kun; Yang, Hong

    2017-11-01

    Propazine is a s-triazine herbicide widely used for controlling weeds for crop production. Its persistence and contamination in environment nagatively affect crop growth and food safety. Elimination of propazine residues in the environment is critical for safe crop production. This study identified a microbial community able to degrade propazine in a farmland soil. About 94% of the applied propazine was degraded within 11 days of incubation when soil was treated with 10mgkg(-1) propazine as the initial concentration. The process was accompanied by increased microbial biomass and activities of soil enzymes. Denaturing gradient gel electrophoresis (DGGE) revealed multiple bacterial strains in the community as well as dynamic change of the composition of microbial community with a reduced microbial diversity (H' from 3.325 to 2.78). Tracking the transcript level of degradative genes AtzB, AtzC and TrzN showed that these genes were induced by propazine and played important roles in the degradation process. The activities of catalase, dehydrogenase and phenol oxidase were stimulated by propazine exposure. Five degradation products (hydroxyl-, methylated-, dimeric-propazine, ammeline and ammelide) were characterized by UPLC-MS(2), revealing a biodegradation of propazine in soil. Several novel methylated and dimeric products of propazine were characterized in thepropazine-exposed soil. These data help understand the pathway, detailed mechanism and efficiency of propazine biodegradation in soil under realistic field condition. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. From ether to acid: A plausible degradation pathway of glycerol dialkyl glycerol tetraethers

    Science.gov (United States)

    Liu, Xiao-Lei; Birgel, Daniel; Elling, Felix J.; Sutton, Paul A.; Lipp, Julius S.; Zhu, Rong; Zhang, Chuanlun; Könneke, Martin; Peckmann, Jörn; Rowland, Steven J.; Summons, Roger E.; Hinrichs, Kai-Uwe

    2016-06-01

    Glycerol dialkyl glycerol tetraethers (GDGTs) are ubiquitous microbial lipids with extensive demonstrated and potential roles as paleoenvironmental proxies. Despite the great attention they receive, comparatively little is known regarding their diagenetic fate. Putative degradation products of GDGTs, identified as hydroxyl and carboxyl derivatives, were detected in lipid extracts of marine sediment, seep carbonate, hot spring sediment and cells of the marine thaumarchaeon Nitrosopumilus maritimus. The distribution of GDGT degradation products in environmental samples suggests that both biotic and abiotic processes act as sinks for GDGTs. More than a hundred newly recognized degradation products afford a view of the stepwise degradation of GDGT via (1) ether bond hydrolysis yielding hydroxyl isoprenoids, namely, GDGTol (glycerol dialkyl glycerol triether alcohol), GMGD (glycerol monobiphytanyl glycerol diether), GDD (glycerol dibiphytanol diether), GMM (glycerol monobiphytanol monoether) and bpdiol (biphytanic diol); (2) oxidation of isoprenoidal alcohols into corresponding carboxyl derivatives and (3) chain shortening to yield C39 and smaller isoprenoids. This plausible GDGT degradation pathway from glycerol ethers to isoprenoidal fatty acids provides the link to commonly detected head-to-head linked long chain isoprenoidal hydrocarbons in petroleum and sediment samples. The problematic C80 to C82 tetraacids that cause naphthenate deposits in some oil production facilities can be generated from H-shaped glycerol monoalkyl glycerol tetraethers (GMGTs) following the same process, as indicated by the distribution of related derivatives in hydrothermally influenced sediments.

  9. Oxidative degradation of N-Nitrosopyrrolidine by the ozone/UV process: Kinetics and pathways.

    Science.gov (United States)

    Chen, Zhi; Fang, Jingyun; Fan, Chihhao; Shang, Chii

    2016-05-01

    N-Nitrosopyrrolidine (NPYR) is an emerging contaminant in drinking water and wastewater. The degradation kinetics and mechanisms of NPYR degradation by the O3/UV process were investigated and compared with those of UV direct photolysis and ozonation. A synergistic effect of ozone and UV was observed in the degradation of NPYR due to the accelerated production of OH• by ozone photolysis. This effect was more pronounced at higher ozone dosages. The second-order rate constants of NPYR reacting with OH• and ozone was determined to be 1.38 (± 0.05) × 10(9) M(-1) s(-1) and 0.31 (± 0.02) M(-1) s(-1), respectively. The quantum yield by direct UV photolysis was 0.3 (± 0.01). An empirical model using Rct (the ratio of the exposure of OH• to that of ozone) was established for NPYR degradation in treated drinking water and showed that the contributions of direct UV photolysis and OH• oxidation on NPYR degradation were both significant. As the reaction proceeded, the contribution by OH• became less important due to the exhausting of ozone. Nitrate was the major product in the O3/UV process by two possible pathways. One is through the cleavage of nitroso group to form NO• followed by hydrolysis, and the other is the oxidation of the intermediates of amines by ozonation.

  10. A novel sucrose synthase pathway for sucrose degradation in cultured sycamore cells.

    Science.gov (United States)

    Huber, S C; Akazawa, T

    1986-08-01

    Enzymes of sucrose degradation and glycolysis in cultured sycamore (Acer pseudoplatanus L.) cells were assayed and characterized in crude extracts and after partial purification, in an attempt to identify pathways for sucrose catabolism. Desalted cell extracts contained similar activities (20-40 nanomoles per milligram protein per minute) of sucrose synthase, neutral invertase, glucokinase, fructokinase, phosphofructokinase, and UDPglucose pyrophosphorylase (assayed with 2 micromolar pyrophosphate (PPi). PPi-linked phosphofructokinase activity was virtually dependent upon fructose 2,6-bisphosphate, and the maximum activity exceeded that of ATP-linked phosphofructokinase. Hexokinase activity, with glucose as substrate, was highly specific for ATP, whereas fructokinase activity was relatively nonspecific. At 1 millimolar nucleoside triphosphate, fructokinase activity decreased in the order: UTP > ATP > CTP > GTP. We propose two pathways for sucrose degradation. One involves invertase action, followed by classical glycolysis of hexose sugars, and the other is a novel pathway initiated by sucrose synthase. The K(m) for sucrose of sucrose synthase was severalfold lower than that of neutral invertase (15 versus 65 millimolar), which may determine carbon partitioning between the two pathways. The sucrose synthase pathway proposed involves cycling of uridylates and PPi. UDPglucose pyrophosphorylase, which is shown to be an effective ;PPi-scavenger,' would consume PPi and form UTP. The UTP could be then utilized in the UTP-linked fructokinase reaction, thereby forming UDP for sucrose synthase. The source of PPi is postulated to arise from the back reaction of PPi-linked phosphofructokinase. Sycamore cells contained a substantial endogenous pool of PPi (about 3 nanomoles per gram fresh weight, roughly 1/10 the amount of ATP in these cells), and sufficient fructose 2,6-bisphosphate (0.09 nanomole per gram fresh weight) to activate the PPi-linked phosphofructokinase. Possible

  11. PINK1-Parkin pathway activity is regulated by degradation of PINK1 in the mitochondrial matrix.

    Directory of Open Access Journals (Sweden)

    Ruth E Thomas

    Full Text Available Loss-of-function mutations in PINK1, which encodes a mitochondrially targeted serine/threonine kinase, result in an early-onset heritable form of Parkinson's disease. Previous work has shown that PINK1 is constitutively degraded in healthy cells, but selectively accumulates on the surface of depolarized mitochondria, thereby initiating their autophagic degradation. Although PINK1 is known to be a cleavage target of several mitochondrial proteases, whether these proteases account for the constitutive degradation of PINK1 in healthy mitochondria remains unclear. To explore the mechanism by which PINK1 is degraded, we performed a screen for mitochondrial proteases that influence PINK1 abundance in the fruit fly Drosophila melanogaster. We found that genetic perturbations targeting the matrix-localized protease Lon caused dramatic accumulation of processed PINK1 species in several mitochondrial compartments, including the matrix. Knockdown of Lon did not decrease mitochondrial membrane potential or trigger activation of the mitochondrial unfolded protein stress response (UPRmt, indicating that PINK1 accumulation in Lon-deficient animals is not a secondary consequence of mitochondrial depolarization or the UPRmt. Moreover, the influence of Lon on PINK1 abundance was highly specific, as Lon inactivation had little or no effect on the abundance of other mitochondrial proteins. Further studies indicated that the processed forms of PINK1 that accumulate upon Lon inactivation are capable of activating the PINK1-Parkin pathway in vivo. Our findings thus suggest that Lon plays an essential role in regulating the PINK1-Parkin pathway by promoting the degradation of PINK1 in the matrix of healthy mitochondria.

  12. Interleukin-1 Acts via the JNK-2 Signaling Pathway to Induce Aggrecan Degradation by Human Chondrocytes.

    Science.gov (United States)

    Ismail, Heba M; Yamamoto, Kazuhiro; Vincent, Tonia L; Nagase, Hideaki; Troeberg, Linda; Saklatvala, Jeremy

    2015-07-01

    Aggrecan enables articular cartilage to bear load and resist compression. Aggrecan loss occurs early in osteoarthritis and rheumatoid arthritis and can be induced by inflammatory cytokines such as interleukin-1 (IL-1). IL-1 induces cleavage of specific aggrecans characteristic of the ADAMTS proteinases. The aim of this study was to identify the intracellular signaling pathways by which IL-1 causes aggrecan degradation by human chondrocytes and to investigate how aggrecanase activity is controlled by chondrocytes. We developed a cell-based assay combining small interfering RNA (siRNA)-induced knockdown with aggrecan degradation assays. Human articular chondrocytes were overlaid with bovine aggrecan after transfection with siRNAs against molecules of the IL-1 signaling pathway. After IL-1 stimulation, released aggrecan fragments were detected with AGEG and ARGS neoepitope antibodies. Aggrecanase activity and tissue inhibitor of metalloproteinases 3 levels were measured by enzyme-linked immunosorbent assay. Low-density lipoprotein receptor-related protein 1 (LRP-1) shedding was analyzed by Western blotting. ADAMTS-5 is a major aggrecanase in human chondrocytes, regulating aggrecan degradation in response to IL-1. The tumor necrosis factor receptor-associated 6 (TRAF-6)/transforming growth factor β-activated kinase 1 (TAK-1)/MKK-4 signaling axis is essential for IL-1-induced aggrecan degradation, while NF-κB is not. Of the 3 MAPKs (ERK, p38, and JNK), only JNK-2 showed a significant role in aggrecan degradation. Chondrocytes constitutively secreted aggrecanase, which was continuously endocytosed by LRP-1, keeping the extracellular level of aggrecanase low. IL-1 induced aggrecanase activity in the medium in a JNK-2-dependent manner, possibly by reducing aggrecanase endocytosis, because IL-1 caused JNK-2-dependent shedding of LRP-1. The signaling axis TRAF-6/TAK-1/MKK-4/JNK-2 mediates IL-1-induced aggrecanolysis. The level of aggrecanase is controlled by its

  13. Involvement of two latex-clearing proteins during rubber degradation and insights into the subsequent degradation pathway revealed by the genome sequence of Gordonia polyisoprenivorans strain VH2.

    Science.gov (United States)

    Hiessl, Sebastian; Schuldes, Jörg; Thürmer, Andrea; Halbsguth, Tobias; Bröker, Daniel; Angelov, Angel; Liebl, Wolfgang; Daniel, Rolf; Steinbüchel, Alexander

    2012-04-01

    The increasing production of synthetic and natural poly(cis-1,4-isoprene) rubber leads to huge challenges in waste management. Only a few bacteria are known to degrade rubber, and little is known about the mechanism of microbial rubber degradation. The genome of Gordonia polyisoprenivorans strain VH2, which is one of the most effective rubber-degrading bacteria, was sequenced and annotated to elucidate the degradation pathway and other features of this actinomycete. The genome consists of a circular chromosome of 5,669,805 bp and a circular plasmid of 174,494 bp with average GC contents of 67.0% and 65.7%, respectively. It contains 5,110 putative protein-coding sequences, including many candidate genes responsible for rubber degradation and other biotechnically relevant pathways. Furthermore, we detected two homologues of a latex-clearing protein, which is supposed to be a key enzyme in rubber degradation. The deletion of these two genes for the first time revealed clear evidence that latex-clearing protein is essential for the microbial utilization of rubber. Based on the genome sequence, we predict a pathway for the microbial degradation of rubber which is supported by previous and current data on transposon mutagenesis, deletion mutants, applied comparative genomics, and literature search.

  14. KCTD1 suppresses canonical Wnt signaling pathway by enhancing β-catenin degradation.

    Directory of Open Access Journals (Sweden)

    Xinxin Li

    Full Text Available The canonical Wnt signaling pathway controls normal embryonic development, cellular proliferation and growth, and its aberrant activity results in human carcinogenesis. The core component in regulation of this pathway is β-catenin, but molecular regulation mechanisms of β-catenin stability are not completely known. Here, our recent studies have shown that KCTD1 strongly inhibits TCF/LEF reporter activity. Moreover, KCTD1 interacted with β-catenin both in vivo by co-immunoprecipitation as well as in vitro through GST pull-down assays. We further mapped the interaction regions to the 1-9 armadillo repeats of β-catenin and the BTB domain of KCTD1, especially Position Ala-30 and His-33. Immunofluorescence analysis indicated that KCTD1 promotes the cytoplasmic accumulation of β-catenin. Furthermore, protein stability assays revealed that KCTD1 enhances the ubiquitination/degradation of β-catenin in a concentration-dependent manner in HeLa cells. And the degradation of β-catenin mediated by KCTD1 was alleviated by the proteasome inhibitor, MG132. In addition, KCTD1-mediated β-catenin degradation was dependent on casein kinase 1 (CK1- and glycogen synthase kinase-3β (GSK-3β-mediated phosphorylation and enhanced by the E3 ubiquitin ligase β-transducin repeat-containing protein (β-TrCP. Moreover, KCTD1 suppressed the expression of endogenous Wnt downstream genes and transcription factor AP-2α. Finally, we found that Wnt pathway member APC and tumor suppressor p53 influence KCTD1-mediated downregulation of β-catenin. These results suggest that KCTD1 functions as a novel inhibitor of Wnt signaling pathway.

  15. Investigating ER-Associated Degradation with RNAi Screening - and Searching for Model Proteins to Do It with

    DEFF Research Database (Denmark)

    Jensen, Njal Winther

    is a sophisticated pathway that recognizes misfolded proteins and targets them for degradation by the 26S proteasome residing in the cytosol. More than 60 diseases including Alzheimer’s disease, Huntington’s disease and Parkinson’s disease have been linked to the ERAD pathway underscoring its crucial role...... for cellular homeostasis. The aim of this thesis has been to gain insight into ERAD. The experimental approach was RNAi screening, which is a fast and efficient method for initial evaluation of a large pool of genes. Since relatively few proteins routinely are used as ERAD substrates, the first goal...

  16. Unraveling the Specific Regulation of the Central Pathway for Anaerobic Degradation of 3-Methylbenzoate*

    Science.gov (United States)

    Juárez, Javier F.; Liu, Huixiang; Zamarro, María T.; McMahon, Stephen; Liu, Huanting; Naismith, James H.; Eberlein, Christian; Boll, Matthias; Carmona, Manuel; Díaz, Eduardo

    2015-01-01

    The mbd cluster encodes the anaerobic degradation of 3-methylbenzoate in the β-proteobacterium Azoarcus sp. CIB. The specific transcriptional regulation circuit that controls the expression of the mbd genes was investigated. The PO, PB1, and P3R promoters responsible for the expression of the mbd genes, their cognate MbdR transcriptional repressor, as well as the MbdR operator regions (ATACN10GTAT) have been characterized. The three-dimensional structure of MbdR has been solved revealing a conformation similar to that of other TetR family transcriptional regulators. The first intermediate of the catabolic pathway, i.e. 3-methylbenzoyl-CoA, was shown to act as the inducer molecule. An additional MbdR-dependent promoter, PA, which contributes to the expression of the CoA ligase that activates 3-methylbenzoate to 3-methylbenzoyl-CoA, was shown to be necessary for an efficient induction of the mbd genes. Our results suggest that the mbd cluster recruited a regulatory system based on the MbdR regulator and its target promoters to evolve a distinct central catabolic pathway that is only expressed for the anaerobic degradation of aromatic compounds that generate 3-methylbenzoyl-CoA as the central metabolite. All these results highlight the importance of the regulatory systems in the evolution and adaptation of bacteria to the anaerobic degradation of aromatic compounds. PMID:25795774

  17. Arginine deiminase pathway genes and arginine degradation variability in Oenococcus oeni strains.

    Science.gov (United States)

    Araque, Isabel; Gil, Joana; Carreté, Ramon; Constantí, Magda; Bordons, Albert; Reguant, Cristina

    2016-03-01

    Trace amounts of the carcinogenic ethyl carbamate can appear in wine as a result of a reaction between ethanol and citrulline, which is produced from arginine degradation by some bacteria used in winemaking. In this study, arginine deiminase (ADI) pathway genes were evaluated in 44 Oenococcus oeni strains from wines originating from several locations in order to establish the relationship between the ability of a strain to degrade arginine and the presence of related genes. To detect the presence of arc genes of the ADI pathway in O. oeni, pairs of primers were designed to amplify arcA, arcB, arcC and arcD1 sequences. All strains contained these four genes. The same primers were used to confirm the organization of these genes in an arcABCD1 operon. Nevertheless, considerable variability in the ability to degrade arginine among these O. oeni strains was observed. Therefore, despite the presence of the arc genes in all strains, the expression patterns of individual genes must be strain dependent and influenced by the different wine conditions. Additionally, the presence of arc genes was also determined in the 57 sequenced strains of O. oeni available in GenBank, and the complete operon was found in 83% of strains derived from wine. The other strains were found to lack the arcB, arcC and arcD genes, but all contained sequences homologous to arcA, and some of them had also ADI activity.

  18. Degradation pathways of low-ethoxylated nonylphenols by isolated bacteria using an improved method.

    Science.gov (United States)

    Zhang, Yu; Gu, Xin; Zhang, Jing; Yang, Min

    2014-01-01

    Nonylphenol ethoxylates (NPEOs) with low ethoxylation degree (NPav₂EO; containing two ethoxy units on average) and estrogenic properties are the intermediate products of nonionic surfactant NPEOs. To better understand the environmental fate of low-ethoxylated NPEOs, phylogenetically diverse low-ethoxylated NPEO-degrading bacteria were isolated from activated sludge using gellan gum as the gelling reagent. Four isolates belonging to four genera, i.e., Pseudomonas sp. NP522b in γ-Proteobacteria, Variovorax sp. NP427b and Ralstonia sp. NP47a in β-Proteobacteria, and Sphingomonas sp. NP42a in α-Proteobacteria were acquired. Ralstonia sp. NP47a or Sphingomonas sp. NP42a, have not been reported for the degradation of low-ethoxylated NPEOs previously. The biotransformation pathways of these isolates were investigated. The first three strains (NP522b, NP427b, and NP47a) exhibited high NPav₂EO oxidation ability by oxidizing the polyethoxy (EO) chain to form low-ethoxylated nonylphenoxy carboxylates, and then further oxidizing the alkyl chain to form carboxyalkylphenol polyethoxycarboxylates. Furthermore, Sphingomonas sp. NP42a degraded NPav2EO through a nonoxidative pathway with nonylphenol monoethoxylate as the dominant product.

  19. Genetic immunization based on the ubiquitin-fusion degradation pathway against Trypanosoma cruzi

    Energy Technology Data Exchange (ETDEWEB)

    Chou, Bin [Department of Microbiology and Immunology, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180 (Japan); Department of Parasitology, Graduate School of Medical Science, Kyushu University, Fukuoka 812-8582 (Japan); Hiromatsu, Kenji, E-mail: khiromatsu@fukuoka-u.ac.jp [Department of Microbiology and Immunology, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180 (Japan); Hisaeda, Hajime; Duan, Xuefeng; Imai, Takashi [Department of Parasitology, Graduate School of Medical Science, Kyushu University, Fukuoka 812-8582 (Japan); Murata, Shigeo; Tanaka, Keiji [Department of Molecular Oncology, The Tokyo Metropolitan Institute of Medical Science, Tokyo 113-8613 (Japan); Himeno, Kunisuke [Department of Parasitology, Graduate School of Medical Science, Kyushu University, Fukuoka 812-8582 (Japan)

    2010-02-12

    Cytotoxic CD8{sup +} T cells are particularly important to the development of protective immunity against the intracellular protozoan parasite, Trypanosoma cruzi, the etiological agent of Chagas disease. We have developed a new effective strategy of genetic immunization by activating CD8{sup +} T cells through the ubiquitin-fusion degradation (UFD) pathway. We constructed expression plasmids encoding the amastigote surface protein-2 (ASP-2) of T. cruzi. To induce the UFD pathway, a chimeric gene encoding ubiquitin fused to ASP-2 (pUB-ASP-2) was constructed. Mice immunized with pUB-ASP-2 presented lower parasitemia and longer survival period, compared with mice immunized with pASP-2 alone. Depletion of CD8{sup +} T cells abolished protection against T. cruzi in mice immunized with pUB-ASP-2 while depletion of CD4{sup +} T cells did not influence the effective immunity. Mice deficient in LMP2 or LMP7, subunits of immunoproteasomes, were not able to develop protective immunity induced. These results suggest that ubiquitin-fused antigens expressed in antigen-presenting cells were effectively degraded via the UFD pathway, and subsequently activated CD8{sup +} T cells. Consequently, immunization with pUB-ASP-2 was able to induce potent protective immunity against infection of T. cruzi.

  20. Chemical modification and degradation of atrazine in Medicago sativa through multiple pathways.

    Science.gov (United States)

    Zhang, Jing Jing; Lu, Yi Chen; Yang, Hong

    2014-10-08

    Atrazine is a member of the triazine herbicide family intensively used to control weeds for crop production. In this study, atrazine residues and its degraded products in alfalfa (Medicago sativa) were characterized using UPLC-TOF-MS/MS. Most of atrazine absorbed in plants was found as chemically modified derivatives like deisopropylated atrazine (DIA), dehydrogenated atrazine (DHA), or methylated atrazine (MEA), and some atrazine derivatives were conjugated through different functional groups such as sugar, glutathione, and amino acids. Interestingly, the specific conjugates DHA+hGSH (homoglutathione) and MEA-HCl+hGSH in alfalfa were detected. These results suggest that atrazine in alfalfa can be degraded through different pathways. The increased activities of glycosyltransferase and glutathione S-transferase were determined to support the atrazine degradation models. The outcome of the work uncovered the detailed mechanism for the residual atrazine accumulation and degradation in alfalfa and will help to evaluate whether the crop is suitable to be cultivated in the atrazine-polluted soil.

  1. Tyrosol degradation via the homogentisic acid pathway in a newly isolated Halomonas strain from olive processing effluents

    OpenAIRE

    Liebgott, Pierre-Pol; Labat, Marc; Amouric, Agnès; Tholozan, Jean-Luc; Lorquin, Jean

    2008-01-01

    To isolate a new Halomonas sp. strain capable of degrading tyrosol, a toxic compound present in olive mill wastewater, through the homogentisic acid (HGA) pathway. A moderately halophilic Gram-negative bacterium belonging to the Halomonas genus and designated strain TYRC17 was isolated from olive processing effluents. This strain was able to completely degrade tyrosol (2-(p-hydroxyphenyl)-ethanol), a toxic compound found in such effluent. Tyrosol degradation begins by an oxidation to 4-hydrox...

  2. Insulin-degrading enzyme is exported via an unconventional protein secretion pathway

    Directory of Open Access Journals (Sweden)

    Leissring Malcolm A

    2009-01-01

    Full Text Available Abstract Insulin-degrading enzyme (IDE is a ubiquitously expressed zinc-metalloprotease that degrades several pathophysiologically significant extracellular substrates, including insulin and the amyloid β-protein (Aβ, and accumulating evidence suggests that IDE dysfunction may be operative in both type 2 diabetes mellitus and Alzheimer disease (AD. Although IDE is well known to be secreted by a variety of cell types, the underlying trafficking pathway(s remain poorly understood. To address this topic, we investigated the effects of known inhibitors or stimulators of protein secretion on the secretion of IDE from murine hepatocytes and HeLa cells. IDE secretion was found to be unaffected by the classical secretion inhibitors brefeldin A (BFA, monensin, or nocodazole, treatments that readily inhibited the secretion of α1-antitrypsin (AAT overexpressed in the same cells. Using a novel cell-based Aβ-degradation assay, we show further that IDE secretion was similarly unaffected by multiple stimulators of protein secretion, including glyburide and 3'-O-(4-benzoylbenzoyl-ATP (Bz-ATP. The calcium ionophore, A23187, increased extracellular IDE activity, but only under conditions that also elicited cytotoxicity. Our results provide the first biochemical evidence that IDE export is not dependent upon the classical secretion pathway, thereby identifying IDE as a novel member of the select class of unconventionally secreted proteins. Further elucidation of the mechanisms underlying IDE secretion, which would be facilitated by the assays described herein, promises to uncover processes that might be defective in disease or manipulated for therapeutic benefit.

  3. Ubiquitin initiates sorting of Golgi and plasma membrane proteins into the vacuolar degradation pathway

    Directory of Open Access Journals (Sweden)

    Scheuring David

    2012-09-01

    Full Text Available Abstract Background In yeast and mammals, many plasma membrane (PM proteins destined for degradation are tagged with ubiquitin. These ubiquitinated proteins are internalized into clathrin-coated vesicles and are transported to early endosomal compartments. There, ubiquitinated proteins are sorted by the endosomal sorting complex required for transport (ESCRT machinery into the intraluminal vesicles of multivesicular endosomes. Degradation of these proteins occurs after endosomes fuse with lysosomes/lytic vacuoles to release their content into the lumen. In plants, some PM proteins, which cycle between the PM and endosomal compartments, have been found to be ubiquitinated, but it is unclear whether ubiquitin is sufficient to mediate internalization and thus acts as a primary sorting signal for the endocytic pathway. To test whether plants use ubiquitin as a signal for the degradation of membrane proteins, we have translationally fused ubiquitin to different fluorescent reporters for the plasma membrane and analyzed their transport. Results Ubiquitin-tagged PM reporters localized to endosomes and to the lumen of the lytic vacuole in tobacco mesophyll protoplasts and in tobacco epidermal cells. The internalization of these reporters was significantly reduced if clathrin-mediated endocytosis was inhibited by the coexpression of a mutant of the clathrin heavy chain, the clathrin hub. Surprisingly, a ubiquitin-tagged reporter for the Golgi was also transported into the lumen of the vacuole. Vacuolar delivery of the reporters was abolished upon inhibition of the ESCRT machinery, indicating that the vacuolar delivery of these reporters occurs via the endocytic transport route. Conclusions Ubiquitin acts as a sorting signal at different compartments in the endomembrane system to target membrane proteins into the vacuolar degradation pathway: If displayed at the PM, ubiquitin triggers internalization of PM reporters into the endocytic transport route

  4. Electrochemical treatment of trypan blue synthetic wastewater and its degradation pathway

    Directory of Open Access Journals (Sweden)

    ANANTHA N. SUBBA RAO

    2013-11-01

    Full Text Available The trypan blue (TB dye synthetic wastewater was treated in presence of chloride ions by electrochemical method. The effect of current density, pH, initial concentration of dye and supporting electrolyte on color and COD removal were investigated. The UV-Vis ab­sorption intensity, chemical oxygen demand (COD, cyclic voltammetry (CV, Fourier transform- infrared spectroscopy (FT-IR, gas chromatography – mass spectrometry (GC-MS analysis were conducted to investigate the kinetics and degradation pathway of TB dye.

  5. The Branched-Chain Dodecylbenzene Sulfonate Degradation Pathway of Pseudomonas aeruginosa W51D Involves a Novel Route for Degradation of the Surfactant Lateral Alkyl Chain

    OpenAIRE

    Campos-García, Jesús; Esteve, Abraham; Vázquez-Duhalt, Rafael; Ramos, Juán Luis; Soberón-Chávez, Gloria

    1999-01-01

    Pseudomonas aeruginosa W51D is able to grow by using branched-chain dodecylbenzene sulfonates (B-DBS) or the terpenic alcohol citronellol as a sole source of carbon. A mutant derived from this strain (W51M1) is unable to degrade citronellol but still grows on B-DBS, showing that the citronellol degradation route is not the main pathway involved in the degradation of the surfactant alkyl moiety. The structures of the main B-DBS isomers and of some intermediates were identified by gas chromatog...

  6. The Branched-Chain Dodecylbenzene Sulfonate Degradation Pathway of Pseudomonas aeruginosa W51D Involves a Novel Route for Degradation of the Surfactant Lateral Alkyl Chain

    Science.gov (United States)

    Campos-García, Jesús; Esteve, Abraham; Vázquez-Duhalt, Rafael; Ramos, Juán Luis; Soberón-Chávez, Gloria

    1999-01-01

    Pseudomonas aeruginosa W51D is able to grow by using branched-chain dodecylbenzene sulfonates (B-DBS) or the terpenic alcohol citronellol as a sole source of carbon. A mutant derived from this strain (W51M1) is unable to degrade citronellol but still grows on B-DBS, showing that the citronellol degradation route is not the main pathway involved in the degradation of the surfactant alkyl moiety. The structures of the main B-DBS isomers and of some intermediates were identified by gas chromatography-mass spectrometric analysis, and a possible catabolic route is proposed. PMID:10427075

  7. Elimination of paternal mitochondria through the lysosomal degradation pathway in C.elegans

    Institute of Scientific and Technical Information of China (English)

    Qinghua Zhou; Haimin Li; Ding Xue

    2011-01-01

    In mammals,the inheritance of mitochondrion and its DNA (mtDNA) is strictly maternal,despite the fact that a sperm can inject up to 100 functional mitochondria into the oocyte during fertilization.The mechanisms responsible for the elimination of the paternal mitochondria remain largely unknown.We report here that this paternal mitochondrial elimination process is conserved in Caenorhabditis elegans,and that the lysosomal pathway actively participates in this process.Molecular and cell biological analyses indicate that in wild-type animals paternal mitoehondria and mtDNA are destroyed within two hours after fertilization.In animals with compromised lysosomes,paternal mitochondria persist until late embryonic stages.Therefore,the lysosomal pathway plays an important role in degrading paternal mitochondria introduced into the oocyte during fertilization.Our study indicates that C.elegans is an excellent animal model for understanding and dissecting this conserved biological process critical for animal development and reproduction.

  8. Willapa - Spartina Eradication 2013

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — Willapa NWR and its partners continue the ongoing and successful program aimed at eradication of the nonnative cordgrass, Spartina alterniflora (Spartina) in Willapa...

  9. Molecular characterization of the Akt-TOR signaling pathway in rainbow trout: potential role in muscle growth/degradation

    Science.gov (United States)

    The Akt-TOR signaling pathway plays a key role in cellular metabolism and muscle growth. Hormone, nutrition and stress factors affect the Akt-TOR pathway by regulating gene transcription, protein synthesis and degradation. In addition, we previously showed that energetic demands elevate during vit...

  10. Def defines a conserved nucleolar pathway that leads p53 to proteasome-independent degradation

    Institute of Scientific and Technical Information of China (English)

    Ting Tao; Hui Shi; Yihong Guan; Delai Huang; Ye Chen; David P Lane; Jun Chen

    2013-01-01

    p53 protein turnover through the ubiquitination pathway is a vital mechanism in the regulation of its transcriptional activity; however,little is known about p53 turnover through proteasome-independent pathway(s).The digestive organ expansion factor (Def) protein is essential for the development of digestive organs.In zebrafish,loss of function of defselectively upregulates the expression of p53 response genes,which raises a question as to what is the relationship between Def and p53.We report here that Def is a nucleolar protein and that loss of function of defleads to the upregulation of p53 protein,which surprisingly accumulates in the nucleoli.Our extensive studies have demonstrated that Def can mediate the degradation of p53 protein and that this process is independent of the proteasome pathway,but dependent on the activity of Calpain3,a cysteine protease.Our findings define a novel nucleolar pathway that regulates the turnover function of p53,which will advance our understanding of p53's role in organogenesis and tumorigenesis.

  11. Investigating ER-Associated Degradation with RNAi Screening - and Searching for Model Proteins to Do It with

    DEFF Research Database (Denmark)

    Jensen, Njal Winther

    is a sophisticated pathway that recognizes misfolded proteins and targets them for degradation by the 26S proteasome residing in the cytosol. More than 60 diseases including Alzheimer’s disease, Huntington’s disease and Parkinson’s disease have been linked to the ERAD pathway underscoring its crucial role...

  12. Kinetics and pathways of ibuprofen degradation by the UV/chlorine advanced oxidation process.

    Science.gov (United States)

    Xiang, Yingying; Fang, Jingyun; Shang, Chii

    2016-03-01

    The UV/chlorine advanced oxidation process (AOP), which forms reactive species such as hydroxyl radicals (HO) and reactive chlorine species (RCS) such as chlorine atoms (Cl) and Cl2(-), is being considered as an alternative to the UV/H2O2 AOP for the degradation of emerging contaminants. This study investigated the kinetics and pathways of the degradation of a recalcitrant pharmaceutical and personal care product (PPCP)-ibuprofen (IBP)-by the UV/chlorine AOP. The degradation of IBP followed the pseudo first-order kinetics. The first-order rate constant was 3.3 times higher in the UV/chlorine AOP than in the UV/H2O2 AOP for a given chemical molar dosage at pH 6. The first-order rate constant decreased from 3.1 × 10(-3) s(-1) to 5.5 × 10(-4) s(-1) with increasing pH from 6 to 9. Both HO and RCS contributed to the degradation, and the contribution of RCS increased from 22% to 30% with increasing pH from 6 to 9. The degradation was initiated by HO-induced hydroxylation and Cl-induced chlorine substitution, and sustained through decarboxylation, demethylation, chlorination and ring cleavage to form more stable products. Significant amounts of chlorinated intermediates/byproducts were formed from the UV/chlorine AOP, and four chlorinated products were newly identified. The yield of total organic chlorine (TOCl) was 31.6 μM after 90% degradation of 50 μM IBP under the experimental conditions. The known disinfection by-products (DBPs) comprised 17.4% of the TOCl. The effects of water matrix in filtered drinking water on the degradation were not significant, demonstrating the practicality of the UV/chlorine AOP for the control of some refractory PPCPs. However, the toxicity of the chlorinated products should be further assessed.

  13. Kinetics and reaction pathways of formaldehyde degradation using the UV-fenton method.

    Science.gov (United States)

    Liu, Xiangxuan; Liang, Jiantao; Wang, Xuanjun

    2011-05-01

    This study was based on the purpose of investigating the reaction rules of formaldehyde (HCHO) as an intermediate product in the degradation of many other organic wastewaters. The process conditions of UV-Fenton method for the degradation of the low concentrations of HCHO were studied in a batch photochemical reactor. The results showed that, when the original HCHO concentration was 30 mg/L, at an operating temperature of 23 degrees C, pH = 3, an H202 dosage of 68 mg/L, and an H2O2-to-Fe2+ mole ratio (H2O2:Fe2+) of 5, 91.89% of the HCHO was removed after 30 minutes. The degradation of HCHO in the UV-Fenton system was basically in accordance with the exponential decay. The kinetic study results showed that the reaction orders of HCHO, Fe2+, and H2O2 in the system were 1.054, 0.510, and 0.728, respectively, and the activation energy (Ea) was 9.85 kJ/mol. The comparison of UV/H2O2, Fenton, and UV-Fenton systems for the degradation of HCHO, and the results of iron catalyst tests showed that the mechanism of UV-Fenton on the degradation of HCHO was through a synergistic effect of Fe2+ and UV light to catalyze the decomposition of H2O2. The introduction of UV irradiation to the Fenton system largely increased the degradation rate of HCHO, mainly as a result of the accelerating effect on the formation of the Fe2+/Fe3+ cycle. The reaction products were analyzed by gas chromatography-mass spectrometry and a chemical oxygen demand (COD) analyzer. The effluent gases also were analyzed by gas chromatography. Based on those results, the reaction pathways of HCHO in the UV-Fenton system were proposed. The qualitative and quantitative analysis of the reaction products and the COD showed that the main intermediate product of the reaction was formic acid, and the further oxidation of it was the rate-limiting step for the degradation of HCHO.

  14. Genomic organisation, activity and distribution analysis of the microbial putrescine oxidase degradation pathway.

    Science.gov (United States)

    Foster, Alexander; Barnes, Nicole; Speight, Robert; Keane, Mark A

    2013-10-01

    The catalytic action of putrescine specific amine oxidases acting in tandem with 4-aminobutyraldehyde dehydrogenase is explored as a degradative pathway in Rhodococcus opacus. By limiting the nitrogen source, increased catalytic activity was induced leading to a coordinated response in the oxidative deamination of putrescine to 4-aminobutyraldehyde and subsequent dehydrogenation to 4-aminobutyrate. Isolating the dehydrogenase by ion exchange chromatography and gel filtration revealed that the enzyme acts principally on linear aliphatic aldehydes possessing an amino moiety. Michaelis-Menten kinetic analysis delivered a Michaelis constant (K(M)=0.014 mM) and maximum rate (Vmax=11.2 μmol/min/mg) for the conversion of 4-aminobutyraldehyde to 4-aminobutyrate. The dehydrogenase identified by MALDI-TOF mass spectrometric analysis (E value=0.031, 23% coverage) belongs to a functionally related genomic cluster that includes the amine oxidase, suggesting their association in a directed cell response. Key regulatory, stress and transport encoding genes have been identified, along with candidate dehydrogenases and transaminases for the further conversion of 4-aminobutyrate to succinate. Genomic analysis has revealed highly similar metabolic gene clustering among members of Actinobacteria, providing insight into putrescine degradation notably among Micrococcaceae, Rhodococci and Corynebacterium by a pathway that was previously uncharacterised in bacteria.

  15. Pathways and Determinants of Early Spontaneous Vegetation Succession in Degraded Lowland of South China

    Institute of Scientific and Technical Information of China (English)

    Wen-Jun Duan; Hai Ran; Sheng-Lei Fu; Qin-Feng Guo; Jun Wang

    2008-01-01

    Continuous and prolonged human disturbances have caused severe degradation of a large portion of lowland in South China, and how to restore such degraded ecosystems becomes an increasing concern. The process and mechanisms of spontaneous succession, which plays an important role in vegetation restoration, have not been adequately examined. To identify the pathways of early spontaneous vegetation succession, 41 plots representing plant communities abandoned over different times were established and Investigated. The communities and indicator species of the vegetation were classified by analyzing the important values of plant species using multivariate analyses. The reaults indicated that the plant species could be classified into nine plant communities repreaenting six succession staages. The pathway and species composition alao changed in the process of succession. We also meaeurad 13 environmental variables of microtopography, soil structure and soil nutrition in each plot to examine the driving forces of auccession and the vegetation-environment relationships. Our resulta ahowed that the environmental variables changed in diverse directions, and that aoil bulk density, soil water capacity and soU acidity were the most important factors.

  16. Degradation Pathway for Eplerenone by Validated Stability Indicating UP-LC Method.

    Science.gov (United States)

    Sudhakar Babu, Kondru; Madireddy, Venkataramanna; Indukuri, Venkata Somaraju

    2012-01-01

    Degradation pathway for eplerenone is established as per ICH recommendations by validated and stability-indicating reverse phase liquid chromatographic method. Eplerenone is subjected to stress conditions of acid, base, oxidation, and thermal and photolysis. Significant degradation is observed in acid and base stress conditions. Four impurities are studied and the major degradant (RRT about 0.31) was identified by LC-MS and spectral analysis. The stress samples are assayed against a qualified reference standard and the mass balance is found close to 99.5%. Efficient chromatographic separation is achieved on a Waters symmetry C18 stationary phase with simple mobile phase combination delivered in gradient mode and quantification is carried at 240 nm at a flow rate of 1.0 mL min(-1). In the developed LC method the resolution between eplerenone and four potential impurities (imp-1, imp-2, imp-3, and imp-4) is found to be greater than 4.0. Regression analysis shows an r value (correlation coefficient) of greater than 0.999 for eplerenone and four potential impurities. This method is capable to detect the impurities of eplerenone at a level of 0.020% with respect to test concentration of 1.0 mg mL(-1) for a 20 μL injection volume. The developed UPLC method is validated with respect to specificity, linearity and range, accuracy, precision, and robustness for impurities and assay determination.

  17. Autophagy-lysosomal pathway is involved in lipid degradation in rat liver.

    Science.gov (United States)

    Skop, V; Cahová, M; Papáčková, Z; Páleníčková, E; Daňková, H; Baranowski, M; Zabielski, P; Zdychová, J; Zídková, J; Kazdová, L

    2012-01-01

    We present data supporting the hypothesis that the lysosomal-autophagy pathway is involved in the degradation of intracellular triacylglycerols in the liver. In primary hepatocytes cultivated in the absence of exogenous fatty acids (FFA), both inhibition of autophagy flux (asparagine) or lysosomal activity (chloroquine) decreased secretion of VLDL (very low density lipoproteins) and formation of FFA oxidative products while the stimulation of autophagy by rapamycine increased some of these parameters. Effect of rapamycine was completely abolished by inactivation of lysosomes. Similarly, when autophagic activity was influenced by cultivating the hepatocytes in "starving" (amino-acid poor medium) or "fed" (serum-supplemented medium) conditions, VLDL secretion and FFA oxidation mirrored the changes in autophagy being higher in starvation and lower in fed state. Autophagy inhibition as well as lysosomal inactivation depressed FFA and DAG (diacylglycerol) formation in liver slices in vitro. In vivo, intensity of lysosomal lipid degradation depends on the formation of autophagolysosomes, i.e. structures bringing the substrate for degradation and lysosomal enzymes into contact. We demonstrated that lysosomal lipase (LAL) activity in liver autophagolysosomal fraction was up-regulated in fasting and down-regulated in fed state together with the increased translocation of LAL and LAMP2 proteins from lysosomal pool to this fraction. Changes in autophagy intensity (LC3-II/LC3-I ratio) followed a similar pattern.

  18. Photocatalytic transformation of sixteen substituted phenylurea herbicides in aqueous semiconductor suspensions: intermediates and degradation pathways.

    Science.gov (United States)

    Fenoll, José; Sabater, Paula; Navarro, Gines; Pérez-Lucas, Gabriel; Navarro, Simón

    2013-01-15

    The photocatalytic degradation of sixteen substituted phenylurea herbicides (PUHs) in pure water has been studied using zinc oxide (ZnO) and titanium dioxide (TiO(2)) as photocatalyst under artificial light irradiation. Photocatalytic experiments showed that the addition of these chalcogenide oxides in tandem with the oxidant (Na(2)S(2)O(8)) strongly enhances the degradation rate of these compounds in comparison with those carried out with ZnO and TiO(2) alone and photolytic tests. Comparison of catalysts showed that ZnO is the most efficient for the removal of such herbicides in optimal conditions and at constant volumetric rate of photon absorption in the photoreactor. Thus, the complete disappearance of all the studied compounds was achieved after 20 min of illumination in the ZnO/Na(2)S(2)O(8) system. The main photocatalytic intermediates detected during the degradation of PUHs were identified. The probable photodegradation pathways were proposed and discussed. The main steps involved: N-demethylation of the N,N-dimethylurea-substituted compounds followed of N-demethylation and N-demethoxylation of the N-methoxy-N-methyl-substituted ureas and hydroxylation of aromatic rings and their aliphatic side-chains of both, parent compounds and intermediates.

  19. WNK4 enhances the degradation of NCC through a sortilin-mediated lysosomal pathway.

    Science.gov (United States)

    Zhou, Bo; Zhuang, Jieqiu; Gu, Dingying; Wang, Hua; Cebotaru, Liudmila; Guggino, William B; Cai, Hui

    2010-01-01

    WNK kinase is a serine/threonine kinase that plays an important role in electrolyte homeostasis. WNK4 significantly inhibits the surface expression of the sodium chloride co-transporter (NCC) by enhancing the degradation of NCC through a lysosomal pathway, but the mechanisms underlying this trafficking are unknown. Here, we investigated the effect of the lysosomal targeting receptor sortilin on NCC expression and degradation. In Cos-7 cells, we observed that the presence of WNK4 reduced the steady-state amount of NCC by approximately half. Co-transfection with truncated sortilin (a dominant negative mutant) prevented this WNK4-induced reduction in NCC. NCC immunoprecipitated with both wild-type sortilin and, to a lesser extent, truncated sortilin. Immunostaining revealed that WNK4 increased the co-localization of NCC with the lysosomal marker cathepsin D, and NCC co-localized with wild-type sortilin, truncated sortilin, and WNK4 in the perinuclear region. These findings suggest that WNK4 promotes NCC targeting to the lysosome for degradation via a mechanism involving sortilin.

  20. Identification of genes and pathways related to phenol degradation in metagenomic libraries from petroleum refinery wastewater.

    Directory of Open Access Journals (Sweden)

    Cynthia C Silva

    Full Text Available Two fosmid libraries, totaling 13,200 clones, were obtained from bioreactor sludge of petroleum refinery wastewater treatment system. The library screening based on PCR and biological activity assays revealed more than 400 positive clones for phenol degradation. From these, 100 clones were randomly selected for pyrosequencing in order to evaluate the genetic potential of the microorganisms present in wastewater treatment plant for biodegradation, focusing mainly on novel genes and pathways of phenol and aromatic compound degradation. The sequence analysis of selected clones yielded 129,635 reads at an estimated 17-fold coverage. The phylogenetic analysis showed Burkholderiales and Rhodocyclales as the most abundant orders among the selected fosmid clones. The MG-RAST analysis revealed a broad metabolic profile with important functions for wastewater treatment, including metabolism of aromatic compounds, nitrogen, sulphur and phosphorus. The predicted 2,276 proteins included phenol hydroxylases and cathecol 2,3- dioxygenases, involved in the catabolism of aromatic compounds, such as phenol, byphenol, benzoate and phenylpropanoid. The sequencing of one fosmid insert of 33 kb unraveled the gene that permitted the host, Escherichia coli EPI300, to grow in the presence of aromatic compounds. Additionally, the comparison of the whole fosmid sequence against bacterial genomes deposited in GenBank showed that about 90% of sequence showed no identity to known sequences of Proteobacteria deposited in the NCBI database. This study surveyed the functional potential of fosmid clones for aromatic compound degradation and contributed to our knowledge of the biodegradative capacity and pathways of microbial assemblages present in refinery wastewater treatment system.

  1. Identification of genes and pathways related to phenol degradation in metagenomic libraries from petroleum refinery wastewater.

    Science.gov (United States)

    Silva, Cynthia C; Hayden, Helen; Sawbridge, Tim; Mele, Pauline; De Paula, Sérgio O; Silva, Lívia C F; Vidigal, Pedro M P; Vicentini, Renato; Sousa, Maíra P; Torres, Ana Paula R; Santiago, Vânia M J; Oliveira, Valéria M

    2013-01-01

    Two fosmid libraries, totaling 13,200 clones, were obtained from bioreactor sludge of petroleum refinery wastewater treatment system. The library screening based on PCR and biological activity assays revealed more than 400 positive clones for phenol degradation. From these, 100 clones were randomly selected for pyrosequencing in order to evaluate the genetic potential of the microorganisms present in wastewater treatment plant for biodegradation, focusing mainly on novel genes and pathways of phenol and aromatic compound degradation. The sequence analysis of selected clones yielded 129,635 reads at an estimated 17-fold coverage. The phylogenetic analysis showed Burkholderiales and Rhodocyclales as the most abundant orders among the selected fosmid clones. The MG-RAST analysis revealed a broad metabolic profile with important functions for wastewater treatment, including metabolism of aromatic compounds, nitrogen, sulphur and phosphorus. The predicted 2,276 proteins included phenol hydroxylases and cathecol 2,3- dioxygenases, involved in the catabolism of aromatic compounds, such as phenol, byphenol, benzoate and phenylpropanoid. The sequencing of one fosmid insert of 33 kb unraveled the gene that permitted the host, Escherichia coli EPI300, to grow in the presence of aromatic compounds. Additionally, the comparison of the whole fosmid sequence against bacterial genomes deposited in GenBank showed that about 90% of sequence showed no identity to known sequences of Proteobacteria deposited in the NCBI database. This study surveyed the functional potential of fosmid clones for aromatic compound degradation and contributed to our knowledge of the biodegradative capacity and pathways of microbial assemblages present in refinery wastewater treatment system.

  2. Education for the Eradication of Poverty

    Directory of Open Access Journals (Sweden)

    C.I. Oriahi

    2010-12-01

    Full Text Available This study examines the possible education for the eradication of poverty in Nigeria. It defines poverty as a state pf shortage or deficiency of meeting basic needs. Majors causes of poverty are overpopulation, illiteracy, unemployment, environmental degradation and government insensitive to the welfare of the people. Effects of poverty include homelessness, malnutrition and starvation, illness, crime, violence and antisocial behaviour like Internet Fraud (Yahoo business and Advance Fee Fraud Populace (419. Some poverty eradication strategies highlighted include: (i Organisation of international workshops on eradication of poverty, (ii Respect for human rights, (iii Quality basic education for girls (iv Meaningful contributions by NGOs, (v Provision of jobs for the people. Some recommendations are made for the way forward.

  3. Synthesis and degradation pathways, functions, and pathology of ceramides and epidermal acylceramides.

    Science.gov (United States)

    Kihara, Akio

    2016-07-01

    Ceramide (Cer) is a structural backbone of sphingolipids and is composed of a long-chain base and a fatty acid. Existence of a variety of Cer species, which differ in chain-length, hydroxylation status, and/or double bond number of either of their hydrophobic chains, has been reported. Ceramide is produced by Cer synthases. Mammals have six Cer synthases (CERS1-6), each of which exhibits characteristic substrate specificity toward acyl-CoAs with different chain-lengths. Knockout mice for each Cer synthase show corresponding, isozyme-specific phenotypes, revealing the functional differences of Cers with different chain-lengths. Cer diversity is especially prominent in epidermis. Changes in Cer levels, composition, and chain-lengths are associated with atopic dermatitis. Acylceramide (acyl-Cer) specifically exists in epidermis and plays an essential role in skin permeability barrier formation. Accordingly, defects in acyl-Cer synthesis cause the cutaneous disorder ichthyosis with accompanying severe skin barrier defects. Although the molecular mechanism by which acyl-Cer is generated was long unclear, most genes involved in its synthesis have been identified recently. In Cer degradation pathways, the long-chain base moiety of Cer is converted to acyl-CoA, which is then incorporated mainly into glycerophospholipids. This pathway generates the lipid mediator sphingosine 1-phosphate. This review will focus on recent advances in our understanding of the synthesis and degradation pathways, physiological functions, and pathology of Cers/acyl-Cers. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Photodegradation of gemfibrozil in aqueous solution under UV irradiation: kinetics, mechanism, toxicity, and degradation pathways.

    Science.gov (United States)

    Ma, Jingshuai; Lv, Wenying; Chen, Ping; Lu, Yida; Wang, Fengliang; Li, Fuhua; Yao, Kun; Liu, Guoguang

    2016-07-01

    The lipid regulator gemfibrozil (GEM) has been reported to be persistent in conventional wastewater treatment plants. This study investigated the photolytic behavior, toxicity of intermediate products, and degradation pathways of GEM in aqueous solutions under UV irradiation. The results demonstrated that the photodegradation of GEM followed pseudo-first-order kinetics, and the pseudo-first-order rate constant was decreased markedly with increasing initial concentrations of GEM and initial pH. The photodegradation of GEM included direct photolysis via (3)GEM(*) and self-sensitization via ROS, where the contribution rates of degradation were 0.52, 90.05, and 8.38 % for ·OH, (1)O2, and (3)GEM(*), respectively. Singlet oxygen ((1)O2) was evidenced by the molecular probe compound, furfuryl alcohol (FFA), and was identified as the primary reactive species in the photolytic process. The steady-state concentrations of (1)O2 increased from (0.324 ± 0.014) × 10(-12) to (1.021 ± 0.040) × 10(-12) mol L(-1), as the initial concentrations of GEM were increased from 5 to 20 mg L(-1). The second-order rate constant for the reaction of GEM with (1)O2 was calculated to be 2.55 × 10(6) M(-1) s(-1). The primary transformation products were identified using HPLC-MS/MS, and possible photodegradation pathways were proposed by hydroxylation, aldehydes reactions, as well as the cleavage of ether side chains. The toxicity of phototransformation product evaluation revealed that photolysis potentially provides a critical pathway for GEM toxicity reduction in potable water and wastewater treatment facilities.

  5. Stress-induced nuclear RNA degradation pathways regulate yeast bromodomain factor 2 to promote cell survival.

    Directory of Open Access Journals (Sweden)

    Kevin Roy

    2014-09-01

    Full Text Available Bromodomain proteins are key regulators of gene expression. How the levels of these factors are regulated in specific environmental conditions is unknown. Previous work has established that expression of yeast Bromodomain factor 2 (BDF2 is limited by spliceosome-mediated decay (SMD. Here we show that BDF2 is subject to an additional layer of post-transcriptional control through RNase III-mediated decay (RMD. We found that the yeast RNase III Rnt1p cleaves a stem-loop structure within the BDF2 mRNA to down-regulate its expression. However, these two nuclear RNA degradation pathways play distinct roles in the regulation of BDF2 expression, as we show that the RMD and SMD pathways of the BDF2 mRNA are differentially activated or repressed in specific environmental conditions. RMD is hyper-activated by salt stress and repressed by hydroxyurea-induced DNA damage while SMD is inactivated by salt stress and predominates during DNA damage. Mutations of cis-acting signals that control SMD and RMD rescue numerous growth defects of cells lacking Bdf1p, and show that SMD plays an important role in the DNA damage response. These results demonstrate that specific environmental conditions modulate nuclear RNA degradation pathways to control BDF2 expression and Bdf2p-mediated gene regulation. Moreover, these results show that precise dosage of Bromodomain factors is essential for cell survival in specific environmental conditions, emphasizing their importance for controlling chromatin structure and gene expression in response to environmental stress.

  6. Aqueous photodegradation of 4-tert-butylphenol: By-products, degradation pathway and theoretical calculation assessment

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Yanlin [State Key Laboratory of Pollution Control and Resources Reuse, College of Environmental Science and Engineering, Tongji University, Shanghai 200092 (China); Shi, Jin; Chen, Hongche [Shanghai Key Laboratory of Atmospheric Particle Pollution and Prevention, Department of Environmental Science & Engineering, Fudan University, Shanghai 200433 (China); Zhao, Jianfu [State Key Laboratory of Pollution Control and Resources Reuse, College of Environmental Science and Engineering, Tongji University, Shanghai 200092 (China); Dong, Wenbo, E-mail: wbdong@fudan.edu.cn [Shanghai Key Laboratory of Atmospheric Particle Pollution and Prevention, Department of Environmental Science & Engineering, Fudan University, Shanghai 200433 (China)

    2016-10-01

    4-tert-butylphenol (4-t-BP), an endocrine disrupting chemical, is widely distributed in natural bodies of water but is difficult to biodegrade. In this study, we focused on the transformation of 4-t-BP in photo-initiated degradation processes. The steady-state photolysis and laser flash photolysis (LFP) experiments were conducted in order to elucidate its degradation mechanism. Identification of products was performed using the GC–MS, LC-MS and theoretical calculation techniques. The oxidation pathway of 4-t-BP by hydroxyl radical (HO·) was also studied and H{sub 2}O{sub 2} was added to produce HO·. 4-tert-butylcatechol and 4-tert-butylphenol dimer were produced in 4-t-BP direct photolysis. 4-tert-butylcatechol and hydroquinone were produced by the oxidation of HO·. But the formation mechanism of 4-tert-butylcatechol in the two processes was different. The benzene ring was fractured in 4-t-BP oxidation process and 29% of TOC was degraded after 16 h irradiation. - Highlights: • Photodegradation of 4-t-BP, an endocrine disrupting chemical, has been investigated. • 3 stable byproducts were identified from photolysis and oxidation processes. • 5 transient by-products were concluded from LFP experiments. • The theoretical calculation was performed to confirm the byproducts. • 4-t-BP was degraded with increasing efficiency: 254 nm < H{sub 2}O{sub 2}/313 nm < H{sub 2}O{sub 2}/254 nm.

  7. Degradation of the synthetic dye amaranth by the fungus Bjerkandera adusta Dec 1: inference of the degradation pathway from an analysis of decolorized products.

    Science.gov (United States)

    Gomi, Nichina; Yoshida, Shuji; Matsumoto, Kazutsugu; Okudomi, Masayuki; Konno, Hiroki; Hisabori, Toru; Sugano, Yasushi

    2011-11-01

    We examined the degradation of amaranth, a representative azo dye, by Bjerkandera adusta Dec 1. The degradation products were analyzed by high performance liquid chromatography (HPLC), visible absorbance, and electrospray ionization time-of-flight mass spectroscopy (ESI-TOF-MS). At the primary culture stage (3 days), the probable reaction intermediates were 1-aminonaphthalene-2,3,6-triol, 4-(hydroxyamino) naphthalene-1-ol, and 2-hydroxy-3-[2-(4-sulfophenyl) hydrazinyl] benzenesulfonic acid. After 10 days, the reaction products detected were 4-nitrophenol, phenol, 2-hydroxy-3-nitrobenzenesulfonic acid, 4-nitrobenzene sulfonic acid, and 3,4'-disulfonyl azo benzene, suggesting that no aromatic amines were created. Manganese-dependent peroxidase activity increased sharply after 3 days culture. Based on these results, we herein propose, for the first time, a degradation pathway for amaranth. Our results suggest that Dec 1 degrades amaranth via the combined activities of peroxidase and hydrolase and reductase action.

  8. Induction of the 5S RNP-Mdm2-p53 ribosomal stress pathway delays the initiation but fails to eradicate established murine acute myeloid leukemia.

    Science.gov (United States)

    Jaako, P; Ugale, A; Wahlestedt, M; Velasco-Hernandez, T; Cammenga, J; Lindström, M S; Bryder, D

    2017-01-01

    Mutations resulting in constitutive activation of signaling pathways that regulate ribosome biogenesis are among the most common genetic events in acute myeloid leukemia (AML). However, whether ribosome biogenesis presents as a therapeutic target to treat AML remains unexplored. Perturbations in ribosome biogenesis trigger the 5S ribonucleoprotein particle (RNP)-Mdm2-p53 ribosomal stress pathway, and induction of this pathway has been shown to have therapeutic efficacy in Myc-driven lymphoma. In the current study we address the physiological and therapeutic role of the 5S RNP-Mdm2-p53 pathway in AML. By utilizing mice that have defective ribosome biogenesis due to downregulation of ribosomal protein S19 (Rps19), we demonstrate that induction of the 5S RNP-Mdm2-p53 pathway significantly delays the initiation of AML. However, even a severe Rps19 deficiency that normally results in acute bone marrow failure has no consistent efficacy on already established disease. Finally, by using mice that harbor a mutation in the Mdm2 gene disrupting its binding to 5S RNP, we show that loss of the 5S RNP-Mdm2-p53 pathway is dispensable for development of AML. Our study suggests that induction of the 5S RNP-Mdm2-p53 ribosomal stress pathway holds limited potential as a single-agent therapy in the treatment of AML.

  9. Removal and Degradation Pathways of Sulfamethoxazole Present in Synthetic Municipal Wastewater via an Anaerobic Membrane Bioreactor

    KAUST Repository

    Sanchez Huerta, Claudia

    2016-05-01

    The current global water crisis in addition to continues contamination of natural water bodies with harmful organic micropollutants (OMPs) have driven the development of new water treatment technologies that allow the efficient removal of such compounds. Among a long list of OMPs, antibiotics are considered as top priority pollutants to be treated due to their great resistance to biological treatments and their potential to develop bacterial resistance. Different approaches, such as membrane-based and advance oxidation processes have been proposed to alleviate or minimize antibiotics discharge into aquatic environments. However most of these processes are costly and generate either matrices with high concentration of OMPs or intermediate products with potentially greater toxicity or persistence. Therefore, this thesis proposes the study of an anaerobic membrane bioreactor (AnMBR) for the treatment of synthetic municipal wastewater containing sulfamethoxazole (SMX), a world widely used antibiotic. Besides the general evaluation of AnMBR performance in the COD removal and biogas production, this research mainly focuses on the SMX removal and its degradation pathway. Thus 5 SMX quantification was performed through solid phase extraction-liquid chromatography/mass spectrometry and the identification of its transformation products (TPs) was assessed by gas chromatography/mass spectrometry technique. The results achieved showed that, working under optimal conditions (35°C, pH 7 and ORP around -380 to -420 mV) and after a biomass adaptation period (maintaining 0.85 VSS/TSS ratio), the AnMBR process provided over 95% COD removal and 95-98% SMX removal, while allowing stable biogas composition and methane production (≈130 mL CH4/g CODremoved). Kinetic analysis through a batch test showed that after 24 h of biological reaction, AnMBR process achieved around 94% SMX removal, indicating a first order kinetic reaction with K= 0.119, which highlights the high degradation

  10. Physiology of deletion mutants in the anaerobic β-myrcene degradation pathway in Castellaniella defragrans

    Directory of Open Access Journals (Sweden)

    Lüddeke Frauke

    2012-09-01

    Full Text Available Abstract Background Monoterpenes present a large and versatile group of unsaturated hydrocarbons of plant origin with widespread use in the fragrance as well as food industry. The anaerobic β-myrcene degradation pathway in Castellaniella defragrans strain 65Phen differs from well known aerobic, monooxygenase-containing pathways. The initial enzyme linalool dehydratase-isomerase ldi/LDI catalyzes the hydration of β-myrcene to (S-(+-linalool and its isomerization to geraniol. A high-affinity geraniol dehydrogenase geoA/GeDH and a geranial dehydrogenase geoB/GaDH contribute to the formation of geranic acid. A genetic system was for the first time applied for the betaproteobacterium to prove in vivo the relevance of the linalool dehydratase-isomerase and the geraniol dehydrogenase. In-frame deletion cassettes were introduced by conjugation and two homologous recombination events. Results Polar effects were absent in the in-frame deletion mutants C. defragrans Δldi and C. defragrans ΔgeoA. The physiological characterization of the strains demonstrated a requirement of the linalool dehydratase-isomerase for growth on acyclic monoterpenes, but not on cyclic monoterpenes. The deletion of geoA resulted in a phenotype with hampered growth rate on monoterpenes as sole carbon and energy source as well as reduced biomass yields. Enzyme assays revealed the presence of a second geraniol dehydrogenase. The deletion mutants were in trans complemented with the broad-host range expression vector pBBR1MCS-4ldi and pBBR1MCS-2geoA, restoring in both cases the wild type phenotype. Conclusions In-frame deletion mutants of genes in the anaerobic β-myrcene degradation revealed novel insights in the in vivo function. The deletion of a high-affinity geraniol dehydrogenase hampered, but did not preclude growth on monoterpenes. A second geraniol dehydrogenase activity was present that contributes to the β-myrcene degradation pathway. Growth on cyclic monoterpenes

  11. Photocatalytic transformation of sixteen substituted phenylurea herbicides in aqueous semiconductor suspensions: Intermediates and degradation pathways

    Energy Technology Data Exchange (ETDEWEB)

    Fenoll, José, E-mail: jose.fenoll@carm.es [Departamento de Calidad y Garantía Alimentaria, Instituto Murciano de Investigación y Desarrollo Agrario y Alimentario (IMIDA), C/Mayor s/n, La Alberca, 30150 Murcia (Spain); Sabater, Paula [Departamento de Calidad y Garantía Alimentaria, Instituto Murciano de Investigación y Desarrollo Agrario y Alimentario (IMIDA), C/Mayor s/n, La Alberca, 30150 Murcia (Spain); Navarro, Gines; Pérez-Lucas, Gabriel; Navarro, Simón [Departamento de Química Agrícola, Geología y Edafología, Facultad de Química, Universidad de Murcia, Campus Universitario de Espinardo, 30100 Murcia (Spain)

    2013-01-15

    Highlights: ► Photocatalytic oxidation of phenylurea herbicides (PUHs) in water. ► The study was performed using ZnO and TiO{sub 2} under artificial light irradiation. ► PUHs were totally degraded using ZnO/Na{sub 2}S{sub 2}O{sub 8}, ZnO, TiO{sub 2}/Na{sub 2}S{sub 2}O{sub 8} and TiO{sub 2}. ► ZnO is the most efficient photocatalyst for the removal of these herbicides. ► 13 intermediates were identified and a mechanism of degradation has been proposed. -- Abstract: The photocatalytic degradation of sixteen substituted phenylurea herbicides (PUHs) in pure water has been studied using zinc oxide (ZnO) and titanium dioxide (TiO{sub 2}) as photocatalyst under artificial light irradiation. Photocatalytic experiments showed that the addition of these chalcogenide oxides in tandem with the oxidant (Na{sub 2}S{sub 2}O{sub 8}) strongly enhances the degradation rate of these compounds in comparison with those carried out with ZnO and TiO{sub 2} alone and photolytic tests. Comparison of catalysts showed that ZnO is the most efficient for the removal of such herbicides in optimal conditions and at constant volumetric rate of photon absorption in the photoreactor. Thus, the complete disappearance of all the studied compounds was achieved after 20 min of illumination in the ZnO/Na{sub 2}S{sub 2}O{sub 8} system. The main photocatalytic intermediates detected during the degradation of PUHs were identified. The probable photodegradation pathways were proposed and discussed. The main steps involved: N-demethylation of the N,N-dimethylurea-substituted compounds followed of N-demethylation and N-demethoxylation of the N-methoxy-N-methyl-substituted ureas and hydroxylation of aromatic rings and their aliphatic side-chains of both, parent compounds and intermediates.

  12. The Degradation Pathway of the Mitophagy Receptor Atg32 Is Re-Routed by a Posttranslational Modification.

    Science.gov (United States)

    Levchenko, Mariia; Lorenzi, Isotta; Dudek, Jan

    2016-01-01

    The outer mitochondrial membrane protein Atg32 is the central receptor for mitophagy, the mitochondria-specific form of autophagy. Atg32 is an unstable protein, and is rapidly degraded under conditions in which mitophagy is not induced. Here we show that Atg32 undergoes a posttranslational modification upon induction of mitophagy. The modification is dependent on the core autophagic machinery, including Atg8, and on the mitophagy-specific adaptor protein Atg11. The modified Atg32 is targeted to the vacuole where it becomes stabilized when vacuolar proteases are deficient. Interestingly, we find that this degradation pathway differs from the degradation pathway of non-modified Atg32, which neither involves vacuolar proteases, nor the proteasome. These analyses reveal that a posttranslational modification discriminates a form of Atg32 targeting mitochondria for mitophagy from that, which escapes mitophagy by rapid degradation.

  13. Photocatalytic degradation of metoprolol tartrate in suspensions of two TiO{sub 2}-based photocatalysts with different surface area. Identification of intermediates and proposal of degradation pathways

    Energy Technology Data Exchange (ETDEWEB)

    Abramovic, Biljana, E-mail: biljana.abramovic@dh.uns.ac.rs [Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Sciences, University of Novi Sad, Trg D. Obradovica 3, 21000 Novi Sad (Serbia); Kler, Sanja, E-mail: sanja.kler@dh.uns.ac.rs [Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Sciences, University of Novi Sad, Trg D. Obradovica 3, 21000 Novi Sad (Serbia); Sojic, Daniela, E-mail: daniela.sojic@dh.uns.ac.rs [Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Sciences, University of Novi Sad, Trg D. Obradovica 3, 21000 Novi Sad (Serbia); Lausevic, Mila, E-mail: milal@tmf.bg.ac.rs [Faculty of Technology and Metallurgy, University of Belgrade, Karnegijeva 4, 11120 Belgrade (Serbia); Radovic, Tanja, E-mail: tradovic@tmf.bg.ac.rs [Faculty of Technology and Metallurgy, University of Belgrade, Karnegijeva 4, 11120 Belgrade (Serbia); Vione, Davide, E-mail: davide.vione@unito.it [Dipartimento di Chimica Analitica, Universita di Torino, Via Pietro Giuria 5, 10125 Torino (Italy)

    2011-12-30

    Highlights: Black-Right-Pointing-Pointer Kinetics and efficiency of photocatalytic degradation of the {beta}{sub 1}-blocker metoprolol tartrate (MET). Black-Right-Pointing-Pointer Two TiO{sub 2} specimens employed. Black-Right-Pointing-Pointer Faster degradation of MET, but slower mineralization, obtained with the TiO{sub 2} specimen having lower surface area. Black-Right-Pointing-Pointer Photocatalytic transformation pathways of MET including mineralization. - Abstract: This study investigates the efficiency of the photocatalytic degradation of metoprolol tartrate (MET), a widely used {beta}{sub 1}-blocker, in TiO{sub 2} suspensions of Wackherr's 'Oxyde de titane standard' and Degussa P25. The study encompasses transformation kinetics and efficiency, identification of intermediates and reaction pathways. In the investigated range of initial concentrations (0.01-0.1 mM), the photocatalytic degradation of MET in the first stage of the reaction followed approximately a pseudo-first order kinetics. The TiO{sub 2} Wackherr induced a significantly faster MET degradation compared to TiO{sub 2} Degussa P25 when relatively high substrate concentrations were used. By examining the effect of ethanol as a scavenger of hydroxyl radicals ({center_dot}OH), it was shown that the reaction with {center_dot}OH played the main role in the photocatalytic degradation of MET. After 240 min of irradiation the reaction intermediates were almost completely mineralized to CO{sub 2} and H{sub 2}O, while the nitrogen was predominantly present as NH{sub 4}{sup +}. Reaction intermediates were studied in detail and a number of them were identified using LC-MS/MS (ESI+), which allowed the proposal of a tentative pathway for the photocatalytic transformation of MET as a function of the TiO{sub 2} specimen.

  14. Cycle Inhibiting Factors (Cifs): Cyclomodulins That Usurp the Ubiquitin-Dependent Degradation Pathway of Host Cells

    Science.gov (United States)

    Taieb, Frédéric; Nougayrède, Jean-Philippe; Oswald, Eric

    2011-01-01

    Cycle inhibiting factors (Cifs) are type III secreted effectors produced by diverse pathogenic bacteria. Cifs are “cyclomodulins” that inhibit the eukaryotic host cell cycle and also hijack other key cellular processes such as those controlling the actin network and apoptosis. This review summarizes current knowledge on Cif since its first characterization in enteropathogenic Escherichia coli, the identification of several xenologues in distant pathogenic bacteria, to its structure elucidation and the recent deciphering of its mode of action. Cif impairs the host ubiquitin proteasome system through deamidation of ubiquitin or the ubiquitin-like protein NEDD8 that regulates Cullin-Ring-ubiquitin Ligase (CRL) complexes. The hijacking of the ubiquitin-dependent degradation pathway of host cells results in the modulation of various cellular functions such as epithelium renewal, apoptosis and immune response. Cif is therefore a powerful weapon in the continuous arm race that characterizes host-bacteria interactions. PMID:22069713

  15. Cycle inhibiting factors (cifs): cyclomodulins that usurp the ubiquitin-dependent degradation pathway of host cells.

    Science.gov (United States)

    Taieb, Frédéric; Nougayrède, Jean-Philippe; Oswald, Eric

    2011-04-01

    Cycle inhibiting factors (Cifs) are type III secreted effectors produced by diverse pathogenic bacteria. Cifs are "cyclomodulins" that inhibit the eukaryotic host cell cycle and also hijack other key cellular processes such as those controlling the actin network and apoptosis. This review summarizes current knowledge on Cif since its first characterization in enteropathogenic Escherichia coli, the identification of several xenologues in distant pathogenic bacteria, to its structure elucidation and the recent deciphering of its mode of action. Cif impairs the host ubiquitin proteasome system through deamidation of ubiquitin or the ubiquitin-like protein NEDD8 that regulates Cullin-Ring-ubiquitin Ligase (CRL) complexes. The hijacking of the ubiquitin-dependent degradation pathway of host cells results in the modulation of various cellular functions such as epithelium renewal, apoptosis and immune response. Cif is therefore a powerful weapon in the continuous arm race that characterizes host-bacteria interactions.

  16. Cycle Inhibiting Factors (Cifs: Cyclomodulins That Usurp the Ubiquitin-Dependent Degradation Pathway of Host Cells

    Directory of Open Access Journals (Sweden)

    Eric Oswald

    2011-03-01

    Full Text Available Cycle inhibiting factors (Cifs are type III secreted effectors produced by diverse pathogenic bacteria. Cifs are “cyclomodulins” that inhibit the eukaryotic host cell cycle and also hijack other key cellular processes such as those controlling the actin network and apoptosis. This review summarizes current knowledge on Cif since its first characterization in enteropathogenic Escherichia coli, the identification of several xenologues in distant pathogenic bacteria, to its structure elucidation and the recent deciphering of its mode of action. Cif impairs the host ubiquitin proteasome system through deamidation of ubiquitin or the ubiquitin-like protein NEDD8 that regulates Cullin-Ring-ubiquitin Ligase (CRL complexes. The hijacking of the ubiquitin-dependent degradation pathway of host cells results in the modulation of various cellular functions such as epithelium renewal, apoptosis and immune response. Cif is therefore a powerful weapon in the continuous arm race that characterizes host-bacteria interactions.

  17. M2-like macrophages are responsible for collagen degradation through a mannose receptor-mediated pathway

    DEFF Research Database (Denmark)

    Madsen, Daniel H; Leonard, Daniel; Masedunskas, Andrius

    2013-01-01

    of the collagen receptors mannose receptor (Mrc1) and urokinase plasminogen activator receptor-associated protein (Endo180 and Mrc2) impaired this intracellular collagen degradation pathway. This study demonstrates the importance of receptor-mediated cellular uptake to collagen turnover in vivo and identifies......Tissue remodeling processes critically depend on the timely removal and remodeling of preexisting collagen scaffolds. Nevertheless, many aspects related to the turnover of this abundant extracellular matrix component in vivo are still incompletely understood. We therefore took advantage of recent...... advances in optical imaging to develop an assay to visualize collagen turnover in situ and identify cell types and molecules involved in this process. Collagen introduced into the dermis of mice underwent cellular endocytosis in a partially matrix metalloproteinase-dependent manner and was subsequently...

  18. Degradation pathways of lamotrigine under advanced treatment by direct UV photolysis, hydroxyl radicals, and ozone.

    Science.gov (United States)

    Keen, Olya S; Ferrer, Imma; Michael Thurman, E; Linden, Karl G

    2014-12-01

    Lamotrigine is recently recognized as a persistent pharmaceutical in the water environment and wastewater effluents. Its degradation was studied under UV and ozone advanced oxidation treatments with reaction kinetics of lamotrigine with ozone (≈4 M(-1)s(-1)), hydroxyl radical [(2.1 ± 0.3) × 10(9)M(-1)s(-1)] and by UV photolysis with low and medium pressure mercury vapor lamps [quantum yields ≈0 and (2.7 ± 0.4)× 10(-4) respectively] determined. All constants were measured at pH 6 and at temperature ≈20°C. The results indicate that lamotrigine is slow to respond to direct photolysis or oxidation by ozone and no attenuation of the contaminant is expected in UV or ozone disinfection applications. The compound reacts rapidly with hydroxyl radicals indicating that advanced oxidation processes would be effective for its treatment. Degradation products were identified under each treatment process using accurate mass time-of-flight spectrometry and pathways of decay were proposed. The main transformation pathways in each process were: dechlorination of the benzene ring during direct photolysis; hydroxyl group addition to the benzene ring during the reaction with hydroxyl radicals; and triazine ring opening after reaction with ozone. Different products that form in each process may be to a varying degree less environmentally stable than the parent lamotrigine. In addition, a novel method of ozone quenching without addition of salts is presented. The new quenching method would allow subsequent mass spectrometry analysis without a solid phase extraction clean-up step. The method involves raising the pH of the sample to approximately 10 for a few seconds and lowering it back and is therefore limited to applications for which temporary pH change is not expected to affect the outcome of the analysis.

  19. Revealing the fate of cell surface human P-glycoprotein (ABCB1): The lysosomal degradation pathway.

    Science.gov (United States)

    Katayama, Kazuhiro; Kapoor, Khyati; Ohnuma, Shinobu; Patel, Atish; Swaim, William; Ambudkar, Indu S; Ambudkar, Suresh V

    2015-10-01

    P-glycoprotein (P-gp) transports a variety of chemically dissimilar amphipathic compounds including anticancer drugs. Although mechanisms of P-gp drug transport are widely studied, the pathways involving its internalization are poorly understood. The present study is aimed at elucidating the pathways involved in degradation of cell surface P-gp. The fate of P-gp at the cell surface was determined by biotinylating cell surface proteins followed by flow cytometry and Western blotting. Our data shows that the half-life of endogenously expressed P-gp is 26.7±1.1 h in human colorectal cancer HCT-15 cells. Treatment of cells with Bafilomycin A1 (BafA1) a vacuolar H+ ATPase inhibitor increased the half-life of P-gp at the cell surface to 36.1±0.5 h. Interestingly, treatment with the proteasomal inhibitors MG132, MG115 or lactacystin alone did not alter the half-life of the protein. When cells were treated with both lysosomal and proteasomal inhibitors (BafA1 and MG132), the half-life was further prolonged to 39-50 h. Functional assays done with rhodamine 123 or calcein-AM, fluorescent substrates of P-gp, indicated that the transport function of P-gp was not affected by either biotinylation or treatment with BafA1 or proteasomal inhibitors. Immunofluorescence studies done with the antibody against lysosomal marker LAMP1 and the P-gp-specific antibody UIC2 in permeabilized cells indicated that intracellular P-gp is primarily localized in the lysosomal compartment. Our results suggest that the lysosomal degradation system could be targeted to increase the sensitivity of P-gp- expressing cancer cells towards chemotherapeutic drugs.

  20. Revealing the fate of cell surface human P-glycoprotein (ABCB1): The Lysosomal Degradation Pathway

    Science.gov (United States)

    Katayama, Kazuhiro; Kapoor, Khyati; Ohnuma, Shinobu; Patel, Atish; Swaim, William; Ambudkar, Indu S.; Ambudkar, Suresh V.

    2015-01-01

    P-glycoprotein (P-gp) transports a variety of chemically dissimilar amphipathic compounds including anticancer drugs. Although mechanisms of P-gp drug transport are widely studied, the pathways involving its internalization are poorly understood. The present study is aimed at elucidating the pathways involved in degradation of cell surface P-gp. The fate of P-gp at the cell surface was determined by biotinylating cell surface proteins followed by flow cytometry and Western blotting. Our data shows that the half-life of endogenously expressed P-gp is 26.7 ± 1.1 h in human colorectal cancer HCT-15 cells. Treatment of cells with Bafilomycin A1 (BafA1) a vacuolar H+ ATPase inhibitor increased the half-life of P-gp at the cell surface to 36.1± 0.5 h. Interestingly, treatment with the proteasomal inhibitors MG132, MG115 or lactacystin alone did not alter the half-life of the protein. When cells were treated with both lysosomal and proteasomal inhibitors (BafA1 and MG132), the half-life was further prolonged to 39-50 h. Functional assays done with rhodamine 123 or calcein-AM, fluorescent substrates of P-gp, indicated that the transport function of P-gp was not affected by either biotinylation or treatment with BafA1 or proteasomal inhibitors. Immunofluorescence studies done with the antibody against lysosomal marker LAMP1 and the P-gp-specific antibody UIC2 in permeabilized cells indicated that intracellular P-gp is primarily localized in the lysosomal compartment. Our results suggest that the lysosomal degradation system could be targeted to increase the sensitivity of P-gp expressing cancer cells towards chemotherapeutic drugs. PMID:26057472

  1. Involvement of PML nuclear bodies in CBP degradation through the ubiquitin-proteasome pathway.

    Science.gov (United States)

    St-Germain, Jonathan R; Chen, Jihong; Li, Qiao

    2008-11-01

    Transcriptional coactivator CBP is involved in the regulation of an array of biological processes including cellular differentiation, proliferation and survival. The function of CBP is critical for proper embryonic development and is relevant in cancer biology. Although much is known about the functional roles of CBP in these cellular processes, fewer studies have assessed what in turn regulates CBP activity per se. It has been reported that CBP colocalizes with PML bodies which are nuclear structures disrupted in acute promyelocytic leukemia. However, the biological relevance of CBP localization to PML nuclear bodies is still unclear. In this study, we demonstrate that histone deacetylase inhibitors such as valproic acid, a therapeutically relevant compound used for the treatment of epilepsy, modulates CBP activity. Valproic acid reduces the steady-state level of CBP by inducing CBP degradation through the ubiquitin-proteasome pathway, while increasing the colocalization of CBP with ubiquitin nuclear speckles and with PML nuclear bodies. Our results suggest that PML nuclear bodies are nuclear sites involved in the ubiquitin-dependent degradation of CBP, providing novel insights in the regulation of CBP function and highlighting the relevance of its localization to PML nuclear bodies.

  2. Characterization of the Complete Uric Acid Degradation Pathway in the Fungal Pathogen Cryptococcus neoformans

    Science.gov (United States)

    Lee, I. Russel; Yang, Liting; Sebetso, Gaseene; Allen, Rebecca; Doan, Thi H. N.; Blundell, Ross; Lui, Edmund Y. L.; Morrow, Carl A.; Fraser, James A.

    2013-01-01

    Degradation of purines to uric acid is generally conserved among organisms, however, the end product of uric acid degradation varies from species to species depending on the presence of active catabolic enzymes. In humans, most higher primates and birds, the urate oxidase gene is non-functional and hence uric acid is not further broken down. Uric acid in human blood plasma serves as an antioxidant and an immune enhancer; conversely, excessive amounts cause the common affliction gout. In contrast, uric acid is completely degraded to ammonia in most fungi. Currently, relatively little is known about uric acid catabolism in the fungal pathogen Cryptococcus neoformans even though this yeast is commonly isolated from uric acid-rich pigeon guano. In addition, uric acid utilization enhances the production of the cryptococcal virulence factors capsule and urease, and may potentially modulate the host immune response during infection. Based on these important observations, we employed both Agrobacterium-mediated insertional mutagenesis and bioinformatics to predict all the uric acid catabolic enzyme-encoding genes in the H99 genome. The candidate C. neoformans uric acid catabolic genes identified were named: URO1 (urate oxidase), URO2 (HIU hydrolase), URO3 (OHCU decarboxylase), DAL1 (allantoinase), DAL2,3,3 (allantoicase-ureidoglycolate hydrolase fusion protein), and URE1 (urease). All six ORFs were then deleted via homologous recombination; assaying of the deletion mutants' ability to assimilate uric acid and its pathway intermediates as the sole nitrogen source validated their enzymatic functions. While Uro1, Uro2, Uro3, Dal1 and Dal2,3,3 were demonstrated to be dispensable for virulence, the significance of using a modified animal model system of cryptococcosis for improved mimicking of human pathogenicity is discussed. PMID:23667704

  3. Pathways for degrading TNT by Thu-Z: a Pantoea sp. strain.

    Science.gov (United States)

    Zou, Liangdong; Lu, Diannan; Liu, Zheng

    2012-12-01

    2,4,6-Trinitrotoluene (TNT), an extensively used and versatile explosive, is harmful in soil and water. In the present study, four bacterial strains capable of degrading TNT have been isolated from contaminated sites and named as Thu-A, Thu-B, Thu-C, and Thu-Z. Thu-Z, which gave the highest degradation efficiency compared to the others, was assigned to the genus Pantoea according to its 16S rRNA gene. Similarities in both biochemical properties and morphology suggested that Thu-Z was a Pantoea sp. strain. Thu-Z was proved to be capable of using TNT as a sole nitrogen source by cleaving NO(2) from the nitroaromatic ring by direct aromatic ring reduction. Under nitrogen-limited conditions, 96.6 % N of TNT was consumed by Thu-Z for growth, which was determined in terms of NaNO(2). Trace nitro reduction metabolites such as 2,4-diamino-6-nitrotoluene (24Dam) and 2,6-diamino-4-nitrotoluene (26Dam) were identified in the presence of (NH(4))(2)SO(4). On the other hand, 4,4',6,6'-tetranitro-2,2'-azoxytoluene (22Azo) and 2,2',6,6'-tetranitro-4,4'-azoxytoluene (44Azo) were detected in the absence of (NH(4))(2)SO(4). These indicated the existence of a dual pathway for Thu-Z, while the direct aromatic ring reduction was predominant. Addition of a nitrogen source ((NH(4))(2)SO(4)) after inoculation stimulated the growth of Thu-Z and accelerated TNT degradation.

  4. Unusual starch degradation pathway via cyclodextrins in the hyperthermophilic sulfate-reducing archaeon Archaeoglobus fulgidus strain 7324.

    Science.gov (United States)

    Labes, Antje; Schönheit, Peter

    2007-12-01

    The hyperthermophilic archaeon Archaeoglobus fulgidus strain 7324 has been shown to grow on starch and sulfate and thus represents the first sulfate reducer able to degrade polymeric sugars. The enzymes involved in starch degradation to glucose 6-phosphate were studied. In extracts of starch-grown cells the activities of the classical starch degradation enzymes, alpha-amylase and amylopullulanase, could not be detected. Instead, evidence is presented here that A. fulgidus utilizes an unusual pathway of starch degradation involving cyclodextrins as intermediates. The pathway comprises the combined action of an extracellular cyclodextrin glucanotransferase (CGTase) converting starch to cyclodextrins and the intracellular conversion of cyclodextrins to glucose 6-phosphate via cyclodextrinase (CDase), maltodextrin phosphorylase (Mal-P), and phosphoglucomutase (PGM). These enzymes, which are all induced after growth on starch, were characterized. CGTase catalyzed the conversion of starch to mainly beta-cyclodextrin. The gene encoding CGTase was cloned and sequenced and showed highest similarity to a glucanotransferase from Thermococcus litoralis. After transport of the cyclodextrins into the cell by a transport system to be defined, these molecules are linearized via a CDase, catalyzing exclusively the ring opening of the cyclodextrins to the respective maltooligodextrins. These are degraded by a Mal-P to glucose 1-phosphate. Finally, PGM catalyzes the conversion of glucose 1-phosphate to glucose 6-phosphate, which is further degraded to pyruvate via the modified Embden-Meyerhof pathway.

  5. Characterization of a novel β-cypermethrin-degrading Aspergillus niger YAT strain and the biochemical degradation pathway of β-cypermethrin.

    Science.gov (United States)

    Deng, Weiqin; Lin, Derong; Yao, Kai; Yuan, Huaiyu; Wang, Zhilong; Li, Jianlong; Zou, Likou; Han, Xinfeng; Zhou, Kang; He, Li; Hu, Xinjie; Liu, Shuliang

    2015-10-01

    Aspergillus niger YAT strain was obtained from Chinese brick tea (Collection number: CGMCC 10,568) and identified on the basis of morphological characteristics and internal transcribed spacer (ITS) sequence. The strain could degrade 54.83 % of β-cypermethrin (β-CY; 50 mg L(-1)) in 7 days and 100 % of 3-phenoxybenzoic acid (3-PBA; 100 mg L(-1)) in 22 h. The half-lives of β-CY and 3-PBA range from 3.573 to 11.748 days and from 5.635 to 12.160 h, respectively. The degradation of β-CY and 3-PBA was further described using first-order kinetic models. The pathway and mechanism of β-CY degraded by YAT were investigated by analyzing the degraded metabolites through high-performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC-MS). Relevant enzymatic activities and substrate utilization were also investigated. β-CY degradation products were analyzed. Results indicated that YAT strain transformed β-CY into 3-PBA. 3-PBA was then gradually transformed into permethric acid, protocatechuic acid, 3-hydroxy-5-phenoxy benzoic acid, gallic acid, and phenol gradually. The YAT strain can also effectively degrade these metabolites. The results indicated that YAT strain has potential applications in bioremediation of pyrethroid insecticide (PI)-contaminated environments and fermented food.

  6. Connecting lignin-degradation pathway with pretreatment inhibitor sensitivity of Cupriavidus necator

    Directory of Open Access Journals (Sweden)

    Wei eWang

    2014-05-01

    Full Text Available To produce lignocellulosic biofuels economically, the complete release of monomers from the plant cell wall components, cellulose, hemicellulose and lignin, through pretreatment and hydrolysis (both enzymatic and chemical, and the efficient utilization of these monomers as carbon sources, is crucial. In addition, the identification and development of robust microbial biofuel production strains that can tolerate the toxic compounds generated during pretreatment and hydrolysis is also essential. In this work, Cupriavidus necator was selected due to its capabilities for utilizing lignin monomers and producing polyhydroxylbutyrate (PHB, a bioplastic as well as an advanced biofuel intermediate. We characterized the growth kinetics of C. necator in pretreated corn stover slurry as well as individually in the presence of 11 potentially toxic compounds in the saccharified slurry. We found that C. necator was sensitive to the saccharified slurry produced from dilute acid pretreated corn stover. Five out of 11 compounds within the slurry were characterized as toxic to C. necator, namely ammonium acetate, furfural, hydroxymethylfurfural (HMF, benzoic acid, and p-coumaric acid. Aldehydes (e.g., furfural and HMF were more toxic than the acetate and the lignin degradation products benzoic acid and p-coumaric acid; furfural was identified as the most toxic compound. Although toxic to C. necator at high concentration, ammonium acetate, benzoic acid, and p-coumaric acid could be utilized by C. necator with a stimulating effect on C. necator growth. Consequently, the lignin degradation pathway of C. necator was reconstructed based on genomic information and literature. The efficient conversion of intermediate catechol to downstream products of cis,cis-muconate or 2-hydroxymuconate-6-semialdehyde may help improve the robustness of C. necator to benzoic acid and p-coumaric acid as well as improve PHB productivity.

  7. Connecting lignin-degradation pathway with pre-treatment inhibitor sensitivity of Cupriavidus necator

    Science.gov (United States)

    Wang, Wei; Yang, Shihui; Hunsinger, Glendon B.; Pienkos, Philip T.; Johnson, David K.

    2014-01-01

    To produce lignocellulosic biofuels economically, the complete release of monomers from the plant cell wall components, cellulose, hemicellulose, and lignin, through pre-treatment and hydrolysis (both enzymatic and chemical), and the efficient utilization of these monomers as carbon sources, is crucial. In addition, the identification and development of robust microbial biofuel production strains that can tolerate the toxic compounds generated during pre-treatment and hydrolysis is also essential. In this work, Cupriavidus necator was selected due to its capabilities for utilizing lignin monomers and producing polyhydroxylbutyrate (PHB), a bioplastic as well as an advanced biofuel intermediate. We characterized the growth kinetics of C. necator in pre-treated corn stover slurry as well as individually in the pre-sence of 11 potentially toxic compounds in the saccharified slurry. We found that C. necator was sensitive to the saccharified slurry produced from dilute acid pre-treated corn stover. Five out of 11 compounds within the slurry were characterized as toxic to C. necator, namely ammonium acetate, furfural, hydroxymethylfurfural (HMF), benzoic acid, and p-coumaric acid. Aldehydes (e.g., furfural and HMF) were more toxic than the acetate and the lignin degradation products benzoic acid and p-coumaric acid; furfural was identified as the most toxic compound. Although toxic to C. necator at high concentration, ammonium acetate, benzoic acid, and p-coumaric acid could be utilized by C. necator with a stimulating effect on C. necator growth. Consequently, the lignin degradation pathway of C. necator was reconstructed based on genomic information and literature. The efficient conversion of intermediate catechol to downstream products of cis,cis-muconate or 2-hydroxymuconate-6-semialdehyde may help improve the robustness of C. necator to benzoic acid and p-coumaric acid as well as improve PHB productivity. PMID:24904560

  8. Connecting Lignin-Degradation Pathway with Pre-Treatment Inhibitor Sensitivity of Cupriavidus necator

    Energy Technology Data Exchange (ETDEWEB)

    Wang, W. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Yang, S. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Hunsinger, G. B. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Pienkos, P. T. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Johnson, D. K. [National Renewable Energy Lab. (NREL), Golden, CO (United States)

    2014-05-27

    In order to produce lignocellulosic biofuels economically, the complete release of monomers from the plant cell wall components, cellulose, hemicellulose, and lignin, through pre-treatment and hydrolysis (both enzymatic and chemical), and the efficient utilization of these monomers as carbon sources, is crucial. In addition, the identification and development of robust microbial biofuel production strains that can tolerate the toxic compounds generated during pre-treatment and hydrolysis is also essential. In this work, Cupriavidus necator was selected due to its capabilities for utilizing lignin monomers and producing polyhydroxylbutyrate (PHB), a bioplastic as well as an advanced biofuel intermediate. We characterized the growth kinetics of C. necator in pre-treated corn stover slurry as well as individually in the pre-sence of 11 potentially toxic compounds in the saccharified slurry. We found that C. necator was sensitive to the saccharified slurry produced from dilute acid pre-treated corn stover. Five out of 11 compounds within the slurry were characterized as toxic to C. necator, namely ammonium acetate, furfural, hydroxymethylfurfural (HMF), benzoic acid, and p-coumaric acid. Aldehydes (e.g., furfural and HMF) were more toxic than the acetate and the lignin degradation products benzoic acid and p-coumaric acid; furfural was identified as the most toxic compound. Although toxic to C. necator at high concentration, ammonium acetate, benzoic acid, and p-coumaric acid could be utilized by C. necator with a stimulating effect on C. necator growth. Consequently, the lignin degradation pathway of C. necator was reconstructed based on genomic information and literature. The efficient conversion of intermediate catechol to downstream products of cis,cis-muconate or 2-hydroxymuconate-6-semialdehyde may help improve the robustness of C. necator to benzoic acid and p-coumaric acid as well as improve PHB productivity.

  9. Connecting lignin-degradation pathway with pre-treatment inhibitor sensitivity of Cupriavidus necator.

    Science.gov (United States)

    Wang, Wei; Yang, Shihui; Hunsinger, Glendon B; Pienkos, Philip T; Johnson, David K

    2014-01-01

    To produce lignocellulosic biofuels economically, the complete release of monomers from the plant cell wall components, cellulose, hemicellulose, and lignin, through pre-treatment and hydrolysis (both enzymatic and chemical), and the efficient utilization of these monomers as carbon sources, is crucial. In addition, the identification and development of robust microbial biofuel production strains that can tolerate the toxic compounds generated during pre-treatment and hydrolysis is also essential. In this work, Cupriavidus necator was selected due to its capabilities for utilizing lignin monomers and producing polyhydroxylbutyrate (PHB), a bioplastic as well as an advanced biofuel intermediate. We characterized the growth kinetics of C. necator in pre-treated corn stover slurry as well as individually in the pre-sence of 11 potentially toxic compounds in the saccharified slurry. We found that C. necator was sensitive to the saccharified slurry produced from dilute acid pre-treated corn stover. Five out of 11 compounds within the slurry were characterized as toxic to C. necator, namely ammonium acetate, furfural, hydroxymethylfurfural (HMF), benzoic acid, and p-coumaric acid. Aldehydes (e.g., furfural and HMF) were more toxic than the acetate and the lignin degradation products benzoic acid and p-coumaric acid; furfural was identified as the most toxic compound. Although toxic to C. necator at high concentration, ammonium acetate, benzoic acid, and p-coumaric acid could be utilized by C. necator with a stimulating effect on C. necator growth. Consequently, the lignin degradation pathway of C. necator was reconstructed based on genomic information and literature. The efficient conversion of intermediate catechol to downstream products of cis,cis-muconate or 2-hydroxymuconate-6-semialdehyde may help improve the robustness of C. necator to benzoic acid and p-coumaric acid as well as improve PHB productivity.

  10. The Whole Genome Sequence of Sphingobium chlorophenolicum L-1: Insights into the Evolution of the Pentachlorophenol Degradation Pathway

    Energy Technology Data Exchange (ETDEWEB)

    Copley, Shelley D. [University of Colorado; Rokicki, Joseph [University of Colorado; Turner, Pernilla [University of Colorado; Daligault, Hajnalka E. [Los Alamos National Laboratory (LANL); Nolan, Matt [U.S. Department of Energy, Joint Genome Institute; Land, Miriam L [ORNL

    2012-01-01

    Sphingobium chlorophenolicum Strain L-1 can mineralize the toxic pesticide pentachlorophenol (PCP). We have sequenced the genome of S. chlorophenolicum Strain L-1. The genome consists of a primary chromosome that encodes most of the genes for core processes, a secondary chromosome that encodes primarily genes that appear to be involved in environmental adaptation, and a small plasmid. The genes responsible for degradation of PCP are found on chromosome 2. We have compared the genomes of S. chlorophenolicum Strain L-1 and Sphingobium japonicum, a closely related Sphingomonad that degrades lindane. Our analysis suggests that the genes encoding the first three enzymes in the PCP degradation pathway were acquired via two different horizontal gene transfer events, and the genes encoding the final two enzymes in the pathway were acquired from the most recent common ancestor of these two bacteria.

  11. EGF Uptake and Degradation Assay to Determine the Effect of HTLV Regulatory Proteins on the ESCRT-Dependent MVB Pathway.

    Science.gov (United States)

    Murphy, Colin; Sheehy, Noreen

    2017-01-01

    The endosomal sorting complex required for transport (ESCRT) pathway plays key roles in multivesicular bodies (MVBs) formation and lysosomal degradation of membrane receptors, viral budding, and midbody abscission during cytokinesis. The epidermal growth factor receptor (EGFR) is regarded as a prototypical cargo of the MVB/ESCRT pathway and following stimulation by epidermal growth factor (EGF) EGFR/EGF complexes are internalized, sorted into MVBs, and degraded by lysosomes or recycled back to the cell membrane. Here, we describe an assay to analyze the effect of human T-cell leukemia (HTLV) regulatory proteins on the functionality of ESCRT-dependent MVB/lysosomal trafficking of EGFR/EGF complexes. This is performed by direct visualization and quantification of the rate of EGF-Alexa595/EGFR internalization and degradation in HeLa cells expressing HTLV regulatory proteins by immunofluorescence and western blot.

  12. Ubiquitin proteasome-dependent degradation of the transcriptional coactivator PGC-1{alpha} via the N-terminal pathway.

    Science.gov (United States)

    Trausch-Azar, Julie; Leone, Teresa C; Kelly, Daniel P; Schwartz, Alan L

    2010-12-17

    PGC-1α is a potent, inducible transcriptional coactivator that exerts control on mitochondrial biogenesis and multiple cellular energy metabolic pathways. PGC-1α levels are controlled in a highly dynamic manner reflecting regulation at both transcriptional and post-transcriptional levels. Here, we demonstrate that PGC-1α is rapidly degraded in the nucleus (t(½ 0.3 h) via the ubiquitin proteasome system. An N-terminal deletion mutant of 182 residues, PGC182, as well as a lysine-less mutant form, are nuclear and rapidly degraded (t(½) 0.5 h), consistent with degradation via the N terminus-dependent ubiquitin subpathway. Both PGC-1α and PGC182 degradation rates are increased in cells under low serum conditions. However, a naturally occurring N-terminal splice variant of 270 residues, NT-PGC-1α is cytoplasmic and stable (t(½>7 h), providing additional evidence that PGC-1α is degraded in the nucleus. These results strongly suggest that the nuclear N terminus-dependent ubiquitin proteasome pathway governs PGC-1α cellular degradation. In contrast, the cellular localization of NT-PCG-1α results in a longer-half-life and possible distinct temporal and potentially biological actions.

  13. Insights from 14C into C loss pathways in degraded peatlands

    Science.gov (United States)

    Evans, Martin; Evans, Chris; Allott, Tim; Stimson, Andrew; Goulsbra, Claire

    2016-04-01

    Peatlands are important global stores of terrestrial carbon. Lowered water tables due to changing climate and direct or indirect human intervention produce a deeper aerobic zone and have the potential to enhance loss of stored carbon from the peat profile. The quasi continuous accumulation of organic matter in active peatlands means that the age of fluvial dissolved organic carbon exported from peatland systems is related to the source depth in the peat profile. Consequently 14C analysis of DOC in waters draining peatlands has the potential not only to tell us about the source of fluvial carbon and the stability of the peatland but also about the dominant hydrological pathways in the peatland system. This paper will present new radiocarbon determinations from peatland streams draining the heavily eroded peatlands of the southern Pennine uplands in the UK. These blanket peatland systems are highly degraded, with extensive bare peat and gully erosion resulting from air pollution during the industrial revolution, overgrazing, wildfire and climatic changes. Deep and extensive gullying has significantly modified the hydrology of these systems leading to local and more widespread drawdown of water table. 14C data from DOC in drainage waters are presented from two catchments; one with extensive gully erosion and the other with a combination of gully erosion and sheet erosion of the peat. At the gully eroded site DOC in drainage waters is as old as 160 BP but at the site with extensive sheet erosion dates of up to 1069 BP are amongst the oldest recorded from blanket peatland globally These data indicate significant degradation of stored carbon from the eroding peatlands. Initial comparisons of the 14C data with modelled water table for the catchments and depth-age curves for catchment peats suggests that erosion of the peat surface, allowing decomposition of exposed older organic material is a potential mechanism producing aged carbon from the eroded catchment. This

  14. Ribosomal Protein Mutations Result in Constitutive p53 Protein Degradation through Impairment of the AKT Pathway.

    Directory of Open Access Journals (Sweden)

    Ana T Antunes

    2015-07-01

    Full Text Available Mutations in ribosomal protein (RP genes can result in the loss of erythrocyte progenitor cells and cause severe anemia. This is seen in patients with Diamond-Blackfan anemia (DBA, a pure red cell aplasia and bone marrow failure syndrome that is almost exclusively linked to RP gene haploinsufficiency. While the mechanisms underlying the cytopenia phenotype of patients with these mutations are not completely understood, it is believed that stabilization of the p53 tumor suppressor protein may induce apoptosis in the progenitor cells. In stark contrast, tumor cells from zebrafish with RP gene haploinsufficiency are unable to stabilize p53 even when exposed to acute DNA damage despite transcribing wild type p53 normally. In this work we demonstrate that p53 has a limited role in eliciting the anemia phenotype of zebrafish models of DBA. In fact, we find that RP-deficient embryos exhibit the same normal p53 transcription, absence of p53 protein, and impaired p53 response to DNA damage as RP haploinsufficient tumor cells. Recently we reported that RP mutations suppress activity of the AKT pathway, and we show here that this suppression results in proteasomal degradation of p53. By re-activating the AKT pathway or by inhibiting GSK-3, a downstream modifier that normally represses AKT signaling, we are able to restore the stabilization of p53. Our work indicates that the anemia phenotype of zebrafish models of DBA is dependent on factors other than p53, and may hold clinical significance for both DBA and the increasing number of cancers revealing spontaneous mutations in RP genes.

  15. HIV/AIDS eradication

    OpenAIRE

    Marsden, Matthew D.; Zack, Jerome A.

    2013-01-01

    Antiretroviral therapy can inhibit HIV replication in patients and prevent progression to AIDS. However, it is not curative. Here we provide an overview of what antiretroviral drugs do and how the virus persists during therapy in rare reservoirs, such as latently infected CD4+ T cells. We also outline several innovative methods that are currently under development to eradicate HIV from infected individuals. These strategies include gene therapy approaches intended to create an HIV-resistant i...

  16. Ozonation degradation of microcystin-LR in aqueous solution: intermediates, byproducts and pathways.

    Science.gov (United States)

    Chang, Jing; Chen, Zhong-lin; Wang, Zhe; Shen, Ji-min; Chen, Qian; Kang, Jing; Yang, Lei; Liu, Xiao-wei; Nie, Chang-xin

    2014-10-15

    The intermediates and byproducts formed during the ozonation of microcystin-LR (MC-LR, m/z = 995.5) and the probable degradation pathway were investigated at different initial molar ratios of ozone to MC-LR ([O3]0/[MC-LR]0). Seven reaction intermediates with m/z ≥ 795.4 were observed by LC/MS, and four of them (m/z = 815.4, 827.3, 853.3 and 855.3) have not been previously reported. Meanwhile, six aldehyde-based byproducts with molecular weights of 30-160 were detected for the first time. Intermediates structures demonstrated that ozone reacted with two sites of MC-LR: the diene bonds in the Adda side chain and the Mdha amino acid in the cyclic structure. The fragment from the Adda side chain oxidative cleavage could be further oxidized to an aldehyde with a molecular weight of 160 at low [O3]0/[MC-LR]0. Meanwhile, the polypeptide structure of MC-LR was difficult to be further oxidized, unless [O3]0/[MC-LR]0 > 10. After further oxidation of the intermediates, five other aldehyde-based byproducts were detected by GC/MS: formaldehyde, acetaldehyde, isovaleraldehyde, glyoxal and methylglyoxal. Formaldehyde, isovaleraldehyde and methylglyoxal were the dominant species. The yields of the aldehydes varied greatly, depending on the value of [O3]0/[MC-LR]0.

  17. REGγ regulates ERα degradation via ubiquitin–proteasome pathway in breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Chai, Fan; Liang, Yan [Breast Disease Center, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); Bi, Jiong [Laboratory of General Surgery, First Affiliated Hospital, Sun Yet-sen University, Guangzhou 510080 (China); Chen, Li; Zhang, Fan [Breast Disease Center, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); Cui, Youhong [Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); Jiang, Jun, E-mail: jcbd@medmail.com.cn [Breast Disease Center, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China)

    2015-01-02

    Highlights: • High expression of REGγ is correlated with ERα status and poor clinical features. • Cell growth, mobility and invasion are significantly impaired by REGγ knockdown. • REGγ indirectly regulates ERα protein expression. - Abstract: REGγ is a proteasome coactivator which regulates proteolytic activity in eukaryotic cells. Abundant lines of evidence have showed that REGγ is over expressed in a number of human carcinomas. However, its precise role in the pathogenesis of cancer is still unclear. In this study, by examining 200 human breast cancer specimens, we demonstrated that REGγ was highly expressed in breast cancers, and the expression of REGγ was positively correlated with breast cancer patient estrogen receptor alpha (ERα) status. Moreover, the expression of REGγ was found positively associated with poor clinical features and low survival rates in ERα positive breast cancer patients. Further cell culture studies using MCF7 and BT474 breast cancer cell lines showed that cell proliferation, motility, and invasion capacities were decreased significantly by REGγ knockdown. Lastly, we demonstrated that REGγ indirectly regulates the degradation of ERα protein via ubiquitin–proteasome pathway. In conclusion, our findings provide the evidence that REGγ expression was positively correlated with ERα status and poor clinical prognosis in ERα positive breast cancer patients. As well, we disclose a new connection between the two molecules that are both highly expressed in most breast cancer cases.

  18. Evolutionary, computational, and biochemical studies of the salicylaldehyde dehydrogenases in the naphthalene degradation pathway

    Science.gov (United States)

    Jia, Baolei; Jia, Xiaomeng; Hyun Kim, Kyung; Ji Pu, Zhong; Kang, Myung-Suk; Ok Jeon, Che

    2017-01-01

    Salicylaldehyde (SAL) dehydrogenase (SALD) is responsible for the oxidation of SAL to salicylate using nicotinamide adenine dinucleotide (NAD+) as a cofactor in the naphthalene degradation pathway. We report the use of a protein sequence similarity network to make functional inferences about SALDs. Network and phylogenetic analyses indicated that SALDs and the homologues are present in bacteria and fungi. The key residues in SALDs were analyzed by evolutionary methods and a molecular simulation analysis. The results showed that the catalytic residue is most highly conserved, followed by the residues binding NAD+ and then the residues binding SAL. A molecular simulation analysis demonstrated the binding energies of the amino acids to NAD+ and/or SAL and showed that a conformational change is induced by binding. A SALD from Alteromonas naphthalenivorans (SALDan) that undergoes trimeric oligomerization was characterized enzymatically. The results showed that SALDan could catalyze the oxidation of a variety of aromatic aldehydes. Site-directed mutagenesis of selected residues binding NAD+ and/or SAL affected the enzyme’s catalytic efficiency, but did not eliminate catalysis. Finally, the relationships among the evolution, catalytic mechanism, and functions of SALD are discussed. Taken together, this study provides an expanded understanding of the evolution, functions, and catalytic mechanism of SALD. PMID:28233868

  19. Electrochemical treatment of iopromide under conditions of reverse osmosis concentrates--elucidation of the degradation pathway.

    Science.gov (United States)

    Lütke Eversloh, C; Henning, N; Schulz, M; Ternes, T A

    2014-01-01

    Application of reverse osmosis for the reuse of treated wastewater on the one hand offers a way to provide high quality effluent waters. On the other hand reverse osmosis concentrates exhibiting highly concentrated contaminants are produced simultaneously. Electrochemical treatment of those concentrates is regarded as one possible answer to the problem of their disposal into surface waters. Nevertheless, due to the diversity of direct and indirect degradation processes during electrolysis, special care has to be taken about the formation of toxic transformation products (TPs). In this study the electrochemical transformation of the X-ray contrast medium iopromide was investigated as a representative of biologically persistent compounds. For this purpose, anodic oxidation at boron doped diamond as well as cathodic reduction using a platinum electrode were considered. Kinetic analyses revealed a transformation of 100 μM iopromide with first order kinetic constants between 0.6 and 1.6 × 10(-4) s(-1) at the beginning and a subsequent increase of the reaction order due to the influence of secondary oxidants formed during electrolysis. Mineralization up to 96% was achieved after about 7.5 h. At shorter treatment times several oxidatively and reductively formed transformation products were detected, whereas deiodinated iopromide represented the major fraction. Nevertheless, the latter exhibited negligible toxicological relevance according to tests on vibrio fisheri. Additional experiments utilizing a divided cell setup enabled the elucidation of the transformation pathway, whereas emerging TPs could be identified by means of high resolution mass spectrometry and MS(n)-fragmentations. During electrolysis the iodine released from Iopromide was found to 90% as iodide and to 10% as iodate even in the open cell experiments, limiting the potential formation of toxic iodo-disinfection by-products. Chlorinated TPs were not found.

  20. Assessing degradation and recovery pathways in lakes impacted by eutrophication using the sediment record

    Directory of Open Access Journals (Sweden)

    Helen eBennion

    2015-08-01

    Full Text Available Efforts to restore enriched lakes have increased yet there remains uncertainty about whether restoration targets can be achieved and over what timescale. Paleoecological techniques, principally diatom analyses, were used to examine the degree of impact and recovery in 12 European lakes subject to eutrophication and subsequent reduction in nutrient loading. Dissimilarity scores showed that all sites experienced progressive deviation from the reference sample (core bottom prior to nutrient reduction, and principal curves indicated gradual compositional change with enrichment. When additive models were applied to the latter, the changes were statistically significant in 9 of the 12 sites. Shifts in diatom composition following reduction in nutrient loading were more equivocal, with a reversal towards the reference flora seen only in four of the deep lakes and one of the shallow lakes. Of these, only two were significant (Lake Bled and Mjøsa. Alternative nutrient sources seem to explain the lack of apparent recovery in the other deep lakes. In three shallow lakes diatom assemblages were replaced by a community associated with lower productivity but not the one seen prior to enrichment. Internal loading and top down control may influence recovery in shallow lakes and climate change may have confounded recovery in several of the study sites. Hence, ecosystem recovery is not simply a reversal of the degradation pathway and may take several decades to complete or, for some lakes, may not take place at all. By assessing ecological change over a decadal to centennial timescale, the study highlights the important role that paleolimnology can play in establishing a benchmark against which managers can evaluate the degree to which their restoration efforts are successful.

  1. Cytoplasmic Hsp70 promotes ubiquitination for endoplasmic reticulum-associated degradation of a misfolded mutant of the yeast plasma membrane ATPase, PMA1.

    Science.gov (United States)

    Han, Sumin; Liu, Yu; Chang, Amy

    2007-09-01

    Cells have a variety of strategies for dealing with misfolded proteins. Heat shock response involves transcriptional induction of chaperones to promote and/or correct folding, and also activation of the ubiquitin/proteasome system to degrade defective proteins. In the secretory pathway, it is primarily luminal misfolded or unassembled proteins that trigger the unfolded protein response which, like heat shock, induces chaperones and components of the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway. To understand cellular response to a misfolded polytopic membrane protein of the secretory pathway, we studied Pma1-D378S, a model ERAD substrate. Expression of misfolded Pma1 induces heat shock response in the absence of increased temperature. Overexpression of HSF1, the transcription factor that mediates heat shock response, increases degradation of Pma1-D378S without temperature upshift. Nevertheless, efficient Pma1-D378S degradation occurs in an hsf1 mutant that maintains basal transcription levels but cannot mediate transcriptional activation. Thus, heat shock protein induction enhances but is not necessary for ERAD. The Ssa group of cytoplasmic Hsp70 chaperones is required for ERAD of both Pma1-D378S and another transmembrane ERAD substrate, Ste6*. In the absence of Ssa chaperones, ubiquitination of both substrates is impaired, resulting in stabilization. We suggest a role for Hsp70 cytoplasmic chaperones in recognition by the endoplasmic reticulum-associated ubiquitination machinery.

  2. Electro-catalytic oxidation of phenacetin with a three-dimensional reactor: Degradation pathway and removal mechanism.

    Science.gov (United States)

    Xiao, Mengshi; Zhang, Yonggang

    2016-06-01

    Phenacetin is a common analgesic, anti-arthritic and anti-rheumatic drug. This study dealt with the degradation of phenacetin in alkaline media using a three-dimensional reactor with particle electrodes. Particular attention was paid to the degradation pathway and the reaction mechanism in the system. Liquid chromatography coupled with time-of-flight mass spectrometry was used to identify the intermediates. The phenacetin was observed to be firstly cut off the branch chains main by direct oxidation, and then the intermediates further degraded to ring opening products by hydroxyl radical resulting from indirect oxidation and finally mineralized to CO2, H2O. A possible removal mechanism was proposed that direct and indirect oxidation together did effect on the pollutants with oxygen.

  3. Effect of surface chemistry of Fe-Ni nanoparticles on mechanistic pathways of azo dye degradation.

    Science.gov (United States)

    Bokare, Alok D; Chikate, Rajeev C; Rode, Chandrashekhar V; Paknikar, Kishore M

    2007-11-01

    The degradation of Orange G, a monoazo dye, in aqueous solutions was investigated using as-synthesized and stored Fe-Ni bimetallic nanoparticles. Batch experiments with a nanocatalyst loading of 3 g/L showed complete dye degradation (150 mg/L) after 10 min of reaction time. HPLC-MS analysis of the degradation products showed that as-synthesized nanoparticles reductively cleaved the azo linkage to produce aniline as the major degradation product. However, 1-year-stored nanoparticles showed an oxidative degradation of Orange G through a hydroxyl-radical induced coupling of parent and/or product molecules. XPS analysis in corroboration with HPLC-MS data showed that the surface chemistry between Fe and Ni in as-synthesized and stored nanoparticles play a crucial role in directing the mode of degradation. Reductive dye degradation using as-synthesized nanoparticles proceeded through hydride transfer from nickel, whereas formation of a Fe2+ -Ni(0) galvanic cell in stored nanoparticles generated hydroxyl radicals from water in a nonFenton type reaction. The latter were responsible for the generation of radical centers on the dye molecule, which led to a coupling-mediated oxidative degradation of Orange G. The generation of hydroxyl radicals is further substantiated with radical quenching experiments using ascorbic acid indicating that stored nanoparticles degrade Orange G through a predominantly oxidative mechanism. HPLC-MS and XPS analysis of dye degradation using as-synthesized nanoparticles exposed to air and water confirmed that the reductive or oxidative degradation capability of Fe-Ni nanoparticles is decided by the time and type of catalyst aging process.

  4. TRIM22 Inhibits the TRAF6-stimulated NF-κB Pathway by Targeting TAB2 for Degradation

    Institute of Scientific and Technical Information of China (English)

    Hui Qiu; Fang Huang; Han Xiao; Binlian Sun; Rongge Yang

    2013-01-01

    Tripartite motif containing 22 (TRIM22),a member of the TRIM/RBCC family,has been reported to activate the nuclear factor-kappa B (NF-κB) pathway in unstimulated macrophage cell lines,but the detailed mechanisms governing this activation remains unclear.We investigated this mechanism in HEK293T cells.We found that overexpression of TRIM22 could activate the NF-κB pathway and conversely,could inhibit the tumor necrosis factor receptor-associated factor 6 (TRAF6)-stimulated NF-κB pathway in HEK293T cells.Further experiments showed that TRIM22 could decrease the self-ubiquitination of TRAF6,and interact with and degrade transforming growth factor-β activated kinase 1 binding protein 2 (TAB2),and that these effects could be partially rescued by a TRIM22 RING domain deletion mutant.Collectively,our data indicate that overexpression of TRIM22 may negatively regulate the TRAF6-stimulated NF-κB pathway by interacting with and degrading TAB2.

  5. Eradication of tetanus

    Science.gov (United States)

    Thwaites, C. L.; Loan, H. T.

    2015-01-01

    Introduction The causative agent of tetanus, Clostridium tetani is widespread in the environment throughout the world and cannot be eradicated. To reduce the number of cases of tetanus efforts are focussed on prevention using vaccination and post-exposure wound care. Sources of data Medline, Pubmed and Cochrane databases; World Health Organization and United Nations Children's Fund publications. Areas of agreement The maternal and neonatal tetanus elimination initiative has resulted in significant reductions in mortality from neonatal tetanus throughout the world. Areas of controversy Although there are few data available it is likely that large numbers of children and adults, particularly men, remain unprotected due to lack of booster immunization. Areas timely for developing research It remains unclear how HIV and malaria affect both responses to vaccination and transplacental transfer of antibodies or how this might affect timing of vaccination doses. PMID:26598719

  6. Hydrocarbon Degradation Pathways used by Coastal Sediment Microbial Communities exposed to Crude Oil

    Science.gov (United States)

    Spaulding-Astudillo, F.; Sharrar, A.; Orcutt, B.

    2016-02-01

    The site-specific microbial community response to crude oil exposure in marine environments is not well described. Moreover, the abundance of genes implicated in long-chain alkane (LCA) and polycyclic aromatic hydrocarbon (PAH) degradation are not well understood. Coastal sediments from the Beaufort Sea, Gulf of Alaska, and Portland Harbor were treated with crude oil and incubated aerobically. Deep-sea sediments from the Gulf of Mexico were treated with the same crude oil and anaerobically incubated in situ for five months before recovery. Cycloclasticus, a known hydrocarbon-degrader, was abundant in all oiled, aerobic samples regardless of temperature, demonstrating a generalist oil-response strategy. Other hydrocarbon degrading bacteria showed differential response to either site or temperature. Primers for alkB, assA, bssA, and ncr, catabolic gene markers for aerobic LCA degradation, anaerobic LCA degradation, anaerobic LCA & PAH degradation, and anaerobic PAH degradation, respectively, were found in literature and tested on DNA extracts in a QPCR-based assay. Gene abundance was site and condition variable.

  7. Biological Feasibility of Measles Eradication

    Science.gov (United States)

    Strebel, Peter

    2011-01-01

    Recent progress in reducing global measles mortality has renewed interest in measles eradication. Three biological criteria are deemed important for disease eradication: (1) humans are the sole pathogen reservoir; (2) accurate diagnostic tests exist; and (3) an effective, practical intervention is available at reasonable cost. Interruption of transmission in large geographical areas for prolonged periods further supports the feasibility of eradication. Measles is thought by many experts to meet these criteria: no nonhuman reservoir is known to exist, accurate diagnostic tests are available, and attenuated measles vaccines are effective and immunogenic. Measles has been eliminated in large geographical areas, including the Americas. Measles eradication is biologically feasible. The challenges for measles eradication will be logistical, political, and financial. PMID:21666201

  8. Glutamine supplementation stimulates protein-synthetic and inhibits protein-degradative signaling pathways in skeletal muscle of diabetic rats.

    Directory of Open Access Journals (Sweden)

    Adriana C Lambertucci

    Full Text Available In this study, we investigated the effect of glutamine (Gln supplementation on the signaling pathways regulating protein synthesis and protein degradation in the skeletal muscle of rats with streptozotocin (STZ-induced diabetes. The expression levels of key regulatory proteins in the synthetic pathways (Akt, mTOR, GSK3 and 4E-BP1 and the degradation pathways (MuRF-1 and MAFbx were determined using real-time PCR and Western blotting in four groups of male Wistar rats; 1 control, non-supplemented with glutamine; 2 control, supplemented with glutamine; 3 diabetic, non-supplemented with glutamine; and 4 diabetic, supplemented with glutamine. Diabetes was induced by the intravenous injection of 65 mg/kg bw STZ in citrate buffer (pH 4.2; the non-diabetic controls received only citrate buffer. After 48 hours, diabetes was confirmed in the STZ-treated animals by the determination of blood glucose levels above 200 mg/dL. Starting on that day, a solution of 1 g/kg bw Gln in phosphate buffered saline (PBS was administered daily via gavage for 15 days to groups 2 and 4. Groups 1 and 3 received only PBS for the same duration. The rats were euthanized, and the soleus muscles were removed and homogenized in extraction buffer for the subsequent measurement of protein and mRNA levels. The results demonstrated a significant decrease in the muscle Gln content in the diabetic rats, and this level increased toward the control value in the diabetic rats receiving Gln. In addition, the diabetic rats exhibited a reduced mRNA expression of regulatory proteins in the protein synthesis pathway and increased expression of those associated with protein degradation. A reduction in the skeletal muscle mass in the diabetic rats was observed and was alleviated partially with Gln supplementation. The data suggest that glutamine supplementation is potentially useful for slowing the progression of muscle atrophy in patients with diabetes.

  9. Identification of dimethylamine monooxygenase in marine bacteria reveals a metabolic bottleneck in the methylated amine degradation pathway.

    Science.gov (United States)

    Lidbury, Ian; Mausz, Michaela A; Scanlan, David J; Chen, Yin

    2017-07-01

    Methylated amines (MAs) are ubiquitous in the marine environment and their subsequent flux into the atmosphere can result in the formation of aerosols and ultimately cloud condensation nuclei. Therefore, these compounds have a potentially important role in climate regulation. Using Ruegeria pomeroyi as a model, we identified the genes encoding dimethylamine (DMA) monooxygenase (dmmABC) and demonstrate that this enzyme degrades DMA to monomethylamine (MMA). Although only dmmABC are required for enzyme activity in recombinant Escherichia coli, we found that an additional gene, dmmD, was required for the growth of R. pomeroyi on MAs. The dmmDABC genes are absent from the genomes of multiple marine bacteria, including all representatives of the cosmopolitan SAR11 clade. Consequently, the abundance of dmmDABC in marine metagenomes was substantially lower than the genes required for other metabolic steps of the MA degradation pathway. Thus, there is a genetic and potential metabolic bottleneck in the marine MA degradation pathway. Our data provide an explanation for the observation that DMA-derived secondary organic aerosols (SOAs) are among the most abundant SOAs detected in fine marine particles over the North and Tropical Atlantic Ocean.

  10. A novel role for ATM in regulating proteasome-mediated protein degradation through suppression of the ISG15 conjugation pathway.

    Directory of Open Access Journals (Sweden)

    Laurence M Wood

    Full Text Available Ataxia Telangiectasia (A-T is an inherited immunodeficiency disorder wherein mutation of the ATM kinase is responsible for the A-T pathogenesis. Although the precise role of ATM in A-T pathogenesis is still unclear, its function in responding to DNA damage has been well established. Here we demonstrate that in addition to its role in DNA repair, ATM also regulates proteasome-mediated protein turnover through suppression of the ISG15 pathway. This conclusion is based on three major pieces of evidence: First, we demonstrate that proteasome-mediated protein degradation is impaired in A-T cells. Second, we show that the reduced protein turnover is causally linked to the elevated expression of the ubiquitin-like protein ISG15 in A-T cells. Third, we show that expression of the ISG15 is elevated in A-T cells derived from various A-T patients, as well as in brain tissues derived from the ATM knockout mice and A-T patients, suggesting that ATM negatively regulates the ISG15 pathway. Our current findings suggest for the first time that proteasome-mediated protein degradation is impaired in A-T cells due to elevated expression of the ISG15 conjugation pathway, which could contribute to progressive neurodegeneration in A-T patients.

  11. Mechanism and Reaction Pathways for Microcystin-LR Degradation through UV/H2O2 Treatment.

    Science.gov (United States)

    Liu, Yafeng; Ren, Jing; Wang, Xiangrong; Fan, Zhengqiu

    2016-01-01

    Microcystin-LR (MCLR) is the most common cyanotoxin in contaminated aquatic systems. MCLR inhibits protein phosphatases 1 and 2A, leading to liver damage and tumor formation. MCLR is relatively stable owing to its cyclic structures. The combined UV/H2O2 technology can degrade MCLR efficiently. The second-order rate constant of the reaction between MCLR and hydroxyl radical (·OH) is 2.79(±0.23)×1010 M-1 s-1 based on the competition kinetics model using nitrobenzene as reference compound. The probable degradation pathway was analyzed through liquid chromatography mass spectrometry. Results suggested that the major destruction pathways of MCLR were initiated by ·OH attack on the benzene ring and diene of the Adda side chain. The corresponding aldehyde or ketone peptide residues were formed through further oxidation. Another minor destruction pathway involved ·OH attack on the methoxy group of the Adda side chain, followed by complete removal of the methoxy group. The combined UV/H2O2 system is a promising technology for MCLR removal in contaminated aquatic systems.

  12. Cell Biology: ERADicating Survival with BOK.

    Science.gov (United States)

    Chipuk, Jerry Edward; Luna-Vargas, Mark P

    2016-06-01

    Mechanistic insights into the function of the pro-apoptotic BCL-2 family member BOK have remained elusive. A recent study shows that healthy cells constitutively degrade BOK via the ER-associated degradation and ubiquitin-proteasome pathways; following proteasome inhibition, BOK is stabilized to initiate a unique pro-apoptotic death program.

  13. Photochemical degradation of atrazine in UV and UV/H2O2 process: pathways and toxic effects of products.

    Science.gov (United States)

    Choi, Hyun-Jin; Kim, Daekeun; Lee, Tae-Jin

    2013-01-01

    The degradation of atrazine in aqueous solution by UV or UV/H2O2 processes, and the toxic effects of the degradation products were explored. The mineralization of atrazine was not observed in the UV irradiation process, resulting in the production of hydroxyatrazine (OIET) as the final product. In the UV/H2O2 process, the final product was ammeline (OAAT), which was obtained by two different pathways of reaction: dechlorination followed by hydroxylation, and the de-alkylation of atrazine. The by-products of the reaction of dechlorination followed by hydroxylation were OIET and hydroxydeethyl atrazine (OIAT), and those of de-alkylation were deisopropyl atrazine (CEAT), deethyl atrazine (CIAT), and deethyldeisopropyl atrazine (CAAT). OIAT and OAAT appeared to be quite stable in the degradation of atrazine by the UV/H2O2 process. In a toxicity test using Daphnia magna, the acute toxic unit (TUa) was less than 1 of TUa (100/EC50, %) in the UV/H2O2 process after 30 min of reaction time, while 1.2 to 1.3 of TUa was observed in the UV process. The TUa values of atrazine and the degradation products have the following decreasing order: OIET> Atrazine> CEAT≈CIAT> CAAT. OIAT and OAAT did not show any toxic effects.

  14. Photolytic and photocatalytic degradation of quinclorac in ultrapure and paddy field water: identification of transformation products and pathways.

    Science.gov (United States)

    Pareja, Lucía; Pérez-Parada, Andrés; Agüera, Ana; Cesio, Verónica; Heinzen, Horacio; Fernández-Alba, Amadeo R

    2012-05-01

    Quinclorac (QNC) is an effective but rather persistent herbicide commonly used in rice production. This herbicide presents a mean persistence in the environment so its residues are considered of environmental relevance. However, few studies have been conducted to investigate its environmental behavior and degradation. In the present work, direct photolysis and TiO(2) photocatalysis of the target compound in ultrapure and paddy field water were investigated. After 10h photolysis in ultrapure water, the concentration of QNC declined 26% and 54% at 250 and 700 W m(-2), respectively. However, the amount of quinclorac in paddy field water remained almost constant under the same irradiation conditions. QNC dissipated completely after 40 min of TiO(2) photocatalysis in ultrapure water, whereas 130 min were necessary to degrade 98% of the initial concentration in paddy field water. Possible QNC photolytic and photocatalytic degradation pathways are proposed after structure elucidation of the main transformation products, through liquid chromatography-electrospray ionization-quadrupole time-of-flight mass spectrometry and exact mass measurements. Pyridine ring hydroxylation at C-9 followed by ring opening and/or oxidative dechlorination were the key steps of QNC degradation. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. Cometabolic degradation of chloramphenicol via a meta-cleavage pathway in a microbial fuel cell and its microbial community.

    Science.gov (United States)

    Zhang, Qinghua; Zhang, Yanyan; Li, Daping

    2017-04-01

    The performance of a microbial fuel cell (MFC) in terms of degradation of chloramphenicol (CAP) was investigated. Approximately 84% of 50mg/L CAP was degraded within 12h in the MFC. A significant interaction of pH, temperature, and initial CAP concentration was found on removal of CAP, and a maximum degradation rate of 96.53% could theoretically be achieved at 31.48°C, a pH of 7.12, and an initial CAP concentration of 106.37mg/L. Moreover, CAP was further degraded through a ring-cleavage pathway. The antibacterial activity of CAP towards Escherichia coli ATCC 25922 and Shewanella oneidensis MR-1 was largely eliminated by MFC treatment. High-throughput sequencing analysis indicated that Azonexus, Comamonas, Nitrososphaera, Chryseobacterium, Azoarcus, Rhodococcus, and Dysgonomonas were the predominant genera in the MFC anode biofilm. In conclusion, the MFC shows potential for the treatment of antibiotic residue-containing wastewater due to its high rates of CAP removal and energy recovery.

  16. Nicotine Dehydrogenase Complexed with 6-Hydroxypseudooxynicotine Oxidase Involved in the Hybrid Nicotine-Degrading Pathway in Agrobacterium tumefaciens S33.

    Science.gov (United States)

    Li, Huili; Xie, Kebo; Yu, Wenjun; Hu, Liejie; Huang, Haiyan; Xie, Huijun; Wang, Shuning

    2016-01-04

    Nicotine, a major toxic alkaloid in tobacco wastes, is degraded by bacteria, mainly via pyridine and pyrrolidine pathways. Previously, we discovered a new hybrid of the pyridine and pyrrolidine pathways in Agrobacterium tumefaciens S33 and characterized its key enzyme 6-hydroxy-3-succinoylpyridine (HSP) hydroxylase. Here, we purified the nicotine dehydrogenase initializing the nicotine degradation from the strain and found that it forms a complex with a novel 6-hydroxypseudooxynicotine oxidase. The purified complex is composed of three different subunits encoded by ndhAB and pno, where ndhA and ndhB overlap by 4 bp and are ∼26 kb away from pno. As predicted from the gene sequences and from chemical analyses, NdhA (82.4 kDa) and NdhB (17.1 kDa) harbor a molybdopterin cofactor and two [2Fe-2S] clusters, respectively, whereas Pno (73.3 kDa) harbors an flavin mononucleotide and a [4Fe-4S] cluster. Mutants with disrupted ndhA or ndhB genes did not grow on nicotine but grew well on 6-hydroxynicotine and HSP, whereas the pno mutant did not grow on nicotine or 6-hydroxynicotine but grew well on HSP, indicating that NdhA and NdhB are responsible for initialization of nicotine oxidation. We successfully expressed pno in Escherichia coli and found that the recombinant Pno presented 2,6-dichlorophenolindophenol reduction activity when it was coupled with 6-hydroxynicotine oxidation. The determination of reaction products catalyzed by the purified enzymes or mutants indicated that NdhAB catalyzed nicotine oxidation to 6-hydroxynicotine, whereas Pno oxidized 6-hydroxypseudooxynicotine to 6-hydroxy-3-succinoylsemialdehyde pyridine. These results provide new insights into this novel hybrid pathway of nicotine degradation in A. tumefaciens S33.

  17. Mankind's Magnificent Milestone: Smallpox Eradication.

    Science.gov (United States)

    Small, Parker A., Jr.; Small, Natalie S.

    1996-01-01

    Illustrates the complex interactions between disease, societal attitudes, and technology by looking at the history of smallpox. Describes one of mankind's most magnificent accomplishments--the eradication of smallpox from the earth. (JRH)

  18. UV photolysis of diclofenac in water; kinetics, degradation pathway and environmental aspects.

    Science.gov (United States)

    Kovacic, Marin; Juretic Perisic, Daria; Biosic, Martina; Kusic, Hrvoje; Babic, Sandra; Loncaric Bozic, Ana

    2016-08-01

    In this study, the photolysis behavior of commonly used anti-inflammatory drug diclofenac (DCF) was investigated using UV-C and UV-A irradiation. In that purpose, DCF conversion kinetics, mineralization of organic content, biodegradability, and toxicity were monitored and compared. The results showed different kinetics of DCF conversion regarding the type of UV source applied. However, in both cases, the mineralization extent reached upon complete DCF conversion is rather low (≤10 %), suggesting that the majority of DCF was transformed into by-products. Formation/degradation of main degradation by-products was monitored using high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS), whereas different profiles were obtained by UV-C and UV-A photolysis. The results of bioassays revealed that biodegradability of DCF solutions remained low through the applied treatments. The toxicity of irradiated DCF solutions was evaluated using Vibrio fischeri. A significant reduction of toxicity, especially in the case of UV-A radiation, was observed upon complete degradation of DCF. In addition to toxicity reduction, calculated Log K OW values of DCF degradation by-products indicate their low potential for bioaccumulation (Log K OW ≤ 3) in comparison to the parent substance.

  19. Peroxisome degradation in Saccharomyces cerevisiae is dependent on machinery of macroautophagy and the Cvt pathway

    NARCIS (Netherlands)

    Hutchins, Maria U.; Veenhuis, Marten; Klionsky, Daniel J.

    1999-01-01

    Organelle biogenesis and turnover are necessary to maintain biochemical processes that are appropriate to the needs of the eukaryotic cell. Specific degradation of organelles in response to changing environmental cues is one aspect of achieving proper metabolic function. For example, the yeast Sacch

  20. Peroxisome degradation in Saccharomyces cerevisiae is dependent on machinery of macroautophagy and the Cvt pathway

    NARCIS (Netherlands)

    Hutchins, Maria U.; Veenhuis, Marten; Klionsky, Daniel J.

    1999-01-01

    Organelle biogenesis and turnover are necessary to maintain biochemical processes that are appropriate to the needs of the eukaryotic cell. Specific degradation of organelles in response to changing environmental cues is one aspect of achieving proper metabolic function. For example, the yeast Sacch

  1. Understanding the degradation pathway of the pesticide, chlorpyrifos by noble metal nanoparticles.

    Science.gov (United States)

    Bootharaju, M S; Pradeep, T

    2012-02-01

    Application of nanoparticles (NPs) in environmental remediation such as water purification requires a detailed understanding of the mechanistic aspects of the interaction between the species involved. Here, an attempt was made to understand the chemistry of noble metal nanoparticle-pesticide interaction, as these nanosystems are being used extensively for water purification. Our model pesticide, chlorpyrifos (CP), belonging to the organophosphorothioate group, is shown to decompose to 3,5,6-trichloro-2-pyridinol (TCP) and diethyl thiophosphate at room temperature over Ag and Au NPs, in supported and unsupported forms. The degradation products were characterized by absorption spectroscopy and electrospray ionization mass spectrometry (ESI MS). These were further confirmed by ESI tandem mass spectrometry. The interaction of CP with NP surfaces was investigated using transmission electron microscopy, energy dispersive analysis of X-rays, Raman spectroscopy, and X-ray photoelectron spectroscopy (XPS). XPS reveals no change in the oxidation state of silver after the degradation of CP. It is proposed that the degradation of CP proceeds through the formation of AgNP-S surface complex, which is confirmed by Raman spectroscopy. In this complex, the P-O bond cleaves to yield a stable aromatic species, TCP. The rate of degradation of CP increases with increase of temperature and pH. Complete degradation of 10 mL of 2 ppm CP solution is achieved in 3 h using 100 mg of supported Ag@citrate NPs on neutral alumina at room temperature at a loading of ∼0.5 wt %. The effect of alumina and monolayer protection of NPs on the degradation of CP is also investigated. The rate of degradation of CP by Ag NPs is greater than that of Au NPs. The results have implications to the application of noble metal NPs for drinking water purification, as pesticide contamination is prevalent in many parts of the world. Study shows that supported Ag and Au NPs may be employed in sustainable

  2. Stability of 6:2 fluorotelomer sulfonate in advanced oxidation processes: degradation kinetics and pathway.

    Science.gov (United States)

    Yang, Xiaoling; Huang, Jun; Zhang, Kunlun; Yu, Gang; Deng, Shubo; Wang, Bin

    2014-03-01

    Perfluorooctane sulfonate (PFOS), a widely used mist suppressant in hard chrome electroplating industry, has been listed in the Stockholm Convention for global ban. 6:2 Fluorotelomer sulfonate (6:2 FTS) acid and salts have been adopted as alternative products in the market, but no data about their abiotic degradation has been reported. In the present study, the degradability of 6:2 FTS potassium salt (6:2 FTS-K) was evaluated under various advanced oxidation processes, including ultraviolet (UV) irradiation, UV with hydrogen peroxide (H2O2), alkaline ozonation (O3, pH = 11), peroxone (O3/H2O2), and Fenton reagent oxidation (Fe(2+)/H2O2). UV/H2O2 was found to be the most effective approach, where the degradation of 6:2 FTS-K followed the pseudo-first-order kinetics. The intermediates were mainly shorter chain perfluoroalkyl carboxylic acid (C7 to C2), while sulfate (SO4 (2-)) and fluoride (F(-)) were found to be the final products. The high yields of SO4 (2-) and F(-) indicate that 6:2 FTS-K can be nearly completely desulfonated and defluorinated under UV/H2O2 condition. The degradation should firstly begin with the substitution of hydrogen atom by hydroxyl radicals, followed by desulfonation, carboxylation, and sequential "flake off" of CF2 unit. Compared with PFOS which is inert in most advanced oxidation processes, 6:2 FTS-K is more degradable as the alternative.

  3. 13C Tracers for Glucose Degrading Pathway Discrimination in Gluconobacter oxydans 621H

    Directory of Open Access Journals (Sweden)

    Steffen Ostermann

    2015-09-01

    Full Text Available Gluconobacter oxydans 621H is used as an industrial production organism due to its exceptional ability to incompletely oxidize a great variety of carbohydrates in the periplasm. With glucose as the carbon source, up to 90% of the initial concentration is oxidized periplasmatically to gluconate and ketogluconates. Growth on glucose is biphasic and intracellular sugar catabolism proceeds via the Entner–Doudoroff pathway (EDP and the pentose phosphate pathway (PPP. Here we studied the in vivo contributions of the two pathways to glucose catabolism on a microtiter scale. In our approach we applied specifically 13C labeled glucose, whereby a labeling pattern in alanine was generated intracellularly. This method revealed a dynamic growth phase-dependent pathway activity with increased activity of EDP in the first and PPP in the second growth phase, respectively. Evidence for a growth phase-independent decarboxylation-carboxylation cycle around the pyruvate node was obtained from 13C fragmentation patterns of alanine. For the first time, down-scaled microtiter plate cultivation together with 13C-labeled substrate was applied for G. oxydans to elucidate pathway operation, exhibiting reasonable labeling costs and allowing for sufficient replicate experiments.

  4. Pathways of nitrobenzene degradation in horizontal subsurface flow constructed wetlands: Effect of intermittent aeration and glucose addition.

    Science.gov (United States)

    Kirui, Wesley K; Wu, Shubiao; Kizito, Simon; Carvalho, Pedro N; Dong, Renjie

    2016-01-15

    Intermittent aeration and addition of glucose were applied to horizontal subsurface flow constructed wetlands in order to investigate the effect on pathways of nitrobenzene (NB) degradation and interactions with microbial nitrogen and sulphur transformations. The experiment was carried out in three phases A, B and C consisting of different NB loading and glucose dosing. For each phase, the effect of aeration was assessed by intermittently aerating one wetland and leaving one unaerated. Regardless of whether or not the wetland was aerated, at an influent NB concentration of 140 mg/L, both wetlands significantly reduced NB to less than 2 mg/L, a reduction efficiency of 98%. However, once the influent NB concentration was increased to 280 mg/L, the aerated wetland had a higher removal performance 82% compared to that of the unaerated wetland 71%. Addition of glucose further intensified the NB removal to 95% in the aerated wetlands and 92% in the unaerated. Aeration of wetlands enhanced NB degradation, but also resulted in higher NB volatilization of 6 mg m(-2) d(-1). The detected high concentration of sulphide 20-60 mg/L in the unaerated wetland gave a strong indication that NB may act as an electron donor to sulphate-reducing bacteria, but this should be further investigated. Aeration positively improved NB removal in constructed wetlands, but resulted in higher NB volatilization. Glucose addition induced co-metabolism to enhance NB degradation.

  5. Electrochemical degradation of sulfonamides at BDD electrode: Kinetics, reaction pathway and eco-toxicity evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Fabiańska, Aleksandra; Białk-Bielińska, Anna; Stepnowski, Piotr [Faculty of Chemistry, University of Gdansk, ul. Wita Stwosza 63, 80-952 Gdansk (Poland); Stolte, Stefan [Faculty of Chemistry, University of Gdansk, ul. Wita Stwosza 63, 80-952 Gdansk (Poland); UFT-Centre of Environmental Research and Sustainable Technology, University of Bremen, Leobener Straße UFT, D-28359 Bremen (Germany); Siedlecka, Ewa Maria, E-mail: ewa.siedlecka@ug.edu.pl [Faculty of Chemistry, University of Gdansk, ul. Wita Stwosza 63, 80-952 Gdansk (Poland)

    2014-09-15

    Highlights: • SNs were electrochemically oxidized at BDD in one compartment reactor. • The efficiency of SN degradation was the highest in effluents from municipal WWTP. • The electro-degradation SNs based on oxidation but reduction was also possible. • Electrochemical oxidation of SNs led in some cases to mixtures toxic to L. minor. - Abstract: The investigation dealt with electrochemical oxidation of five sulfonamides (SNs): sulfadiazine (SDZ), sulfathiazole (STZ), sulfamerazine (SMR), sulfamethazine (SMN) and sulfadimethoxine (SDM) in aqueous solution at boron-doped diamond (BDD) electrode. All studied sulfonamides were degraded according to a pseudo first order kinetics. The structure of SNs had no significant effect on the values of pseudo first order rate constants. Increased degradation efficiency was observed in higher temperature and in acidic pH. Due to the presence of chlorine and nitrate SNs were more effectively oxidized from municipal wastewater treatment plant (WWTP) effluents than from pure supporting electrolyte Na{sub 2}SO{sub 4}. The intermediates identified by LC–MS and GC–MS analysis suggested that the hydroxyl radicals attack mainly the S-N bond, but also the aromatic ring systems (aniline, pyrimidine or triazole) of SNs. Finally, the toxicity of the SNs solutions and effluents after electrochemical treatment was assessed through the measurement of growth inhibition of green algae (Scenedesmus vacualatus) and duckweed (Lemna minor). Toxicity of SMR, STZ, SMN solutions before and after electrochemical oxidation and SDM solution after the process in L. minor test was observed. No significant toxicity of studied SNs was observed in algae test.

  6. Coupled Metabolic and Photolytic Pathway for Degradation of Pyridinedicarboxylic Acids, Especially Dipicolinic Acid

    OpenAIRE

    Amador, José A.; Taylor, Barrie F.

    1990-01-01

    Three isomers of pyridinedicarboxylic acid (PDCA) (2,3-, 2,5-, and 2,6-PDCA) were partially oxidized by marine bacteria when grown aerobically on the corresponding phthalate analogs. The metabolites, unlike the parent PDCAs, absorbed light in the solar actinic range (wavelengths greater than 300 nm) and were readily degraded in sunlight. The principal product from 2,6-PDCA (dipicolinic acid) metabolism was extracted from a culture fluid, purified by column chromatography, and analyzed by UV-v...

  7. Enhanced catalytic degradation of ciprofloxacin with FeS2/SiO2 microspheres as heterogeneous Fenton catalyst: Kinetics, reaction pathways and mechanism.

    Science.gov (United States)

    Diao, Zeng-Hui; Xu, Xiang-Rong; Jiang, Dan; Li, Gang; Liu, Jin-Jun; Kong, Ling-Jun; Zuo, Lin-Zi

    2017-04-05

    In this study, the application of FeS2/SiO2 microspheres as a catalyst to activate H2O2 for the degradation of ciprofloxacin (CIP) was systematically investigated. Results demonstrated that the presence of SiO2 microspheres on the surface of FeS2 could effectively make the reaction of aqueous Fe(2+) and H2O2 smoothly continuous by controlling the release of aqueous Fe(2+) from FeS2. Nearly 100% of CIP was degraded after 60min under the optimum conditions. A superior performance on the CIP degradation and high reusability of the catalyst was obtained in FeS2/SiO2 microspheres activated H2O2 system. A low concentration of ethylene diamine tetraacetie acid (EDTA) did positively affect the degradation rate of CIP. A synergetic effect between adsorption and oxidation processes contributed to the significant enhancement of CIP degradation. Seven oxidation intermediates were identified during the CIP degradation process, and the direct HO oxidation proved to be a main CIP degradation pathway. For degradation pathway of CIP, oxidation of piperazine ring would be its first step, followed by cleavage of the heterocyclic ring. Subsequently, the substitution, hydroxylation and decarboxylation processes occurred. This is the first report on the feasibility of FeS2/SiO2 microspheres activated H2O2 system for the enhanced degradation of CIP. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Population sinks resulting from degraded habitats of an obligate life-history pathway.

    Science.gov (United States)

    Hickford, Michael J H; Schiel, David R

    2011-05-01

    Many species traverse multiple habitats across ecosystems to complete their life histories. Degradation of critical, life stage-specific habitats can therefore lead to population bottlenecks and demographic deficits in sub-populations. The riparian zone of waterways is one of the most impacted areas of the coastal zone because of urbanisation, deforestation, farming and livestock grazing. We hypothesised that sink populations can result from alterations of habitats critical to the early life stages of diadromous fish that use this zone, and tested this with field-based sampling and experiments. We found that for Galaxias maculatus, one of the most widely distributed fishes of the southern hemisphere, obligate riparian spawning habitat was very limited and highly vulnerable to disturbance across 14 rivers in New Zealand. Eggs were laid only during spring tides, in the highest tidally influenced vegetation of waterways. Egg survival increased to >90% when laid in three riparian plant species and where stem densities were great enough to prevent desiccation, compared to no survival where vegetation was comprised of other species or was less dense. Experimental exclusion of livestock, one of the major sources of riparian degradation in rural waterways, resulted in quick regeneration, a tenfold increase in egg laying by fish and a threefold increase in survival, compared to adjacent controls. Overall, there was an inverse relationship between river size and egg production. Some of the largest rivers had little or no spawning habitat and very little egg production, effectively becoming sink populations despite supporting large adult populations, whereas some of the smallest pristine streams produced millions of eggs. We demonstrate that even a wide-ranging species with many robust adult populations can be compromised if a stage-specific habitat required to complete a life history is degraded by localised or more diffuse impacts.

  9. Pathways and substrate-specific regulation of amino acid degradation in Phaeobacter inhibens DSM 17395 (archetype of the marine Roseobacter clade).

    Science.gov (United States)

    Drüppel, Katharina; Hensler, Michael; Trautwein, Kathleen; Koßmehl, Sebastian; Wöhlbrand, Lars; Schmidt-Hohagen, Kerstin; Ulbrich, Marcus; Bergen, Nils; Meier-Kolthoff, Jan P; Göker, Markus; Klenk, Hans-Peter; Schomburg, Dietmar; Rabus, Ralf

    2014-01-01

    Combining omics and enzymatic approaches, catabolic routes of nine selected amino acids (tryptophan, phenylalanine, methionine, leucine, isoleucine, valine, histidine, lysine and threonine) were elucidated in substrate-adapted cells of Phaeobacter inhibens DSM 17395 (displaying conspicuous morphotypes). The catabolic network [excluding tricarboxylic acid (TCA) cycle] was reconstructed from 71 genes (scattered across the chromosome; one-third newly assigned), with 69 encoded proteins and 20 specific metabolites identified, and activities of 10 different enzymes determined. For example, Ph. inhibens DSM 17395 does not degrade lysine via the widespread saccharopine pathway but might rather employ two parallel pathways via 5-aminopentanoate or 2-aminoadipate. Tryptophan degradation proceeds via kynurenine and 2-aminobenzoate; the latter is metabolized as known from Azoarcus evansii. Histidine degradation is analogous to the Pseudomonas-type Hut pathway via N-formyl-l-glutamate. For threonine, only one of the three genome-predicted degradation pathways (employing threonine 3-dehydrogenase) is used. Proteins of the individual peripheral degradation sequences in Ph. inhibens DSM 17395 were apparently substrate-specifically formed contrasting the non-modulated TCA cycle enzymes. Comparison of genes for the reconstructed amino acid degradation network in Ph. inhibens DSM 17395 across 27 other complete genomes of Roseobacter clade members revealed most of them to be widespread among roseobacters.

  10. Insulin-degrading enzyme secretion from astrocytes is mediated by an autophagy-based unconventional secretory pathway in Alzheimer disease.

    Science.gov (United States)

    Son, Sung Min; Cha, Moon-Yong; Choi, Heesun; Kang, Seokjo; Choi, Hyunjung; Lee, Myung-Shik; Park, Sun Ah; Mook-Jung, Inhee

    2016-05-01

    The secretion of proteins that lack a signal sequence to the extracellular milieu is regulated by their transition through the unconventional secretory pathway. IDE (insulin-degrading enzyme) is one of the major proteases of amyloid beta peptide (Aβ), a presumed causative molecule in Alzheimer disease (AD) pathogenesis. IDE acts in the extracellular space despite having no signal sequence, but the underlying mechanism of IDE secretion extracellularly is still unknown. In this study, we found that IDE levels were reduced in the cerebrospinal fluid (CSF) of patients with AD and in pathology-bearing AD-model mice. Since astrocytes are the main cell types for IDE secretion, astrocytes were treated with Aβ. Aβ increased the IDE levels in a time- and concentration-dependent manner. Moreover, IDE secretion was associated with an autophagy-based unconventional secretory pathway, and depended on the activity of RAB8A and GORASP (Golgi reassembly stacking protein). Finally, mice with global haploinsufficiency of an essential autophagy gene, showed decreased IDE levels in the CSF in response to an intracerebroventricular (i.c.v.) injection of Aβ. These results indicate that IDE is secreted from astrocytes through an autophagy-based unconventional secretory pathway in AD conditions, and that the regulation of autophagy is a potential therapeutic target in addressing Aβ pathology.

  11. Regulation of protein degradation pathways by amino acids and insulin in skeletal muscle of neonatal pigs

    Institute of Scientific and Technical Information of China (English)

    Agus Suryawan; Teresa ADavis

    2014-01-01

    Background:The rapid gain in lean mass in neonates requires greater rates of protein synthesis than degradation. We previously delineated the molecular mechanisms by which insulin and amino acids, especially leucine, modulate skeletal muscle protein synthesis and how this changes with development. In the current study, we identified mechanisms involved in protein degradation regulation. In experiment 1, 6-and 26-d-old pigs were studied during 1) euinsulinemic-euglycemic-euaminoacidemic, 2) euinsulinemic-euglycemic-hyperaminoacidemic, and 3) hyperinsulinemic-euglycemic-euaminoacidemic clamps for 2 h. In experiment 2, 5-d-old pigs were studied during 1) euinsulinemic-euglycemic-euaminoacidemic-euleucinemic, 2) euinsulinemic-euglycemic-hypoaminoacidemic-hyperleucinemic, and 3) euinsulinemic-euglycemic-euaminoacidemic-hyperleucinemic clamps for 24 h. We determined in muscle indices of ubiquitin-proteasome, i.e., atrogin-1 (MAFbx) and muscle RING-finger protein-1 (MuRF1) and autophagy-lysosome systems, i.e., unc51-like kinase 1 (UKL1), microtubule-associated protein light chain 3 (LC3), and lysosomal-associated membrane protein 2 (Lamp-2). For comparison, we measured ribosomal protein S6 (rpS6) and eukaryotic initiation factor 4E (eIF4E) activation, components of translation initiation. Results:Abundance of atrogin-1, but not MuRF1, was greater in 26-than 6-d-old pigs and was not affected by insulin, amino acids, or leucine. Abundance of ULK1 and LC3 was higher in younger pigs and not affected by treatment. The LC3-II/LC3-I ratio was reduced and ULK1 phosphorylation increased by insulin, amino acids, and leucine. These responses were more profound in younger pigs. Abundance of Lamp-2 was not affected by treatment or development. Abundance of eIF4E, but not rpS6, was higher in 6-than 26-d-old-pigs but unaffected by treatment. Phosphorylation of eIF4E was not affected by treatment, however, insulin, amino acids, and leucine stimulated rpS6 phosphorylation, and the

  12. Bacterial degradation of benzoate: cross-regulation between aerobic and anaerobic pathways

    OpenAIRE

    2012-01-01

    We have studied for the first time the transcriptional regulatory circuit that controls the expression of the box genes encoding the aerobic hybrid pathway used to assimilate benzoate via coenzyme A (CoA) derivatives in bacteria. The promoters responsible for the expression of the box cluster in the β-proteobacterium Azoarcus sp., their cognate transcriptional repressor, the BoxR protein, and the inducer molecule (benzoyl-CoA) have been characterized. The BoxR protein shows a significant sequ...

  13. Impact of the NGF maturation and degradation pathway on the cortical cholinergic system phenotype.

    Science.gov (United States)

    Allard, Simon; Leon, Wanda C; Pakavathkumar, Prateep; Bruno, Martin A; Ribeiro-da-Silva, Alfredo; Cuello, A Claudio

    2012-02-08

    Cortical cholinergic atrophy plays a significant role in the cognitive loss seen with aging and in Alzheimer's disease (AD), but the mechanisms leading to it remain unresolved. Nerve growth factor (NGF) is the neurotrophin responsible for the phenotypic maintenance of basal forebrain cholinergic neurons in the mature and fully differentiated CNS. In consequence, its implication in cholinergic atrophy has been suspected; however, no mechanistic explanation has been provided. We have previously shown that the precursor of NGF (proNGF) is cleaved extracellularly by plasmin to form mature NGF (mNGF) and that mNGF is degraded by matrix metalloproteinase 9. Using cognitive-behavioral tests, Western blotting, and confocal and electron microscopy, this study demonstrates that a pharmacologically induced chronic failure in extracellular NGF maturation leads to a reduction in mNGF levels, proNGF accumulation, cholinergic degeneration, and cognitive impairment in rats. It also shows that inhibiting NGF degradation increases endogenous levels of the mature neurotrophin and increases the density of cortical cholinergic boutons. Together, the data point to a mechanism explaining cholinergic loss in neurodegenerative conditions such as AD and provide a potential therapeutic target for the protection or restoration of this CNS transmitter system in aging and AD.

  14. Bioremediation of soil polluted with crude oil and its derivatives: Microorganisms, degradation pathways, technologies

    Directory of Open Access Journals (Sweden)

    Beškoski Vladimir P.

    2012-01-01

    Full Text Available The contamination of soil and water with petroleum and its products occurs due to accidental spills during exploitation, transport, processing, storing and use. In order to control the environmental risks caused by petroleum products a variety of techniques based on physical, chemical and biological methods have been used. Biological methods are considered to have a comparative advantage as cost effective and environmentally friendly technologies. Bioremediation, defined as the use of biological systems to destroy and reduce the concentrations of hazardous waste from contaminated sites, is an evolving technology for the removal and degradation of petroleum hydrocarbons as well as industrial solvents, phenols and pesticides. Microorganisms are the main bioremediation agents due to their diverse metabolic capacities. In order to enhance the rate of pollutant degradation the technology optimizes the conditions for the growth of microorganisms present in soil by aeration, nutrient addition and, if necessary, by adding separately prepared microorganisms cultures. The other factors that influence the efficiency of process are temperature, humidity, presence of surfactants, soil pH, mineral composition, content of organic substance of soil as well as type and concentration of contaminant. This paper presents a review of our ex situ bioremediation procedures successfully implemented on the industrial level. This technology was used for treatment of soils contaminated by crude oil and its derivatives originated from refinery as well as soils polluted with oil fuel and transformer oil.

  15. Electrochemical degradation of sulfonamides at BDD electrode: kinetics, reaction pathway and eco-toxicity evaluation.

    Science.gov (United States)

    Fabiańska, Aleksandra; Białk-Bielińska, Anna; Stepnowski, Piotr; Stolte, Stefan; Siedlecka, Ewa Maria

    2014-09-15

    The investigation dealt with electrochemical oxidation of five sulfonamides (SNs): sulfadiazine (SDZ), sulfathiazole (STZ), sulfamerazine (SMR), sulfamethazine (SMN) and sulfadimethoxine (SDM) in aqueous solution at boron-doped diamond (BDD) electrode. All studied sulfonamides were degraded according to a pseudo first order kinetics. The structure of SNs had no significant effect on the values of pseudo first order rate constants. Increased degradation efficiency was observed in higher temperature and in acidic pH. Due to the presence of chlorine and nitrate SNs were more effectively oxidized from municipal wastewater treatment plant (WWTP) effluents than from pure supporting electrolyte Na2SO4. The intermediates identified by LC-MS and GC-MS analysis suggested that the hydroxyl radicals attack mainly the SN bond, but also the aromatic ring systems (aniline, pyrimidine or triazole) of SNs. Finally, the toxicity of the SNs solutions and effluents after electrochemical treatment was assessed through the measurement of growth inhibition of green algae (Scenedesmus vacualatus) and duckweed (Lemna minor). Toxicity of SMR, STZ, SMN solutions before and after electrochemical oxidation and SDM solution after the process in L. minor test was observed. No significant toxicity of studied SNs was observed in algae test. Copyright © 2014. Published by Elsevier B.V.

  16. Time evolution and competing pathways in photodegradation of trifluralin and three of its major degradation products.

    Science.gov (United States)

    Tagle, Martín G Sarmiento; Laura Salum, María; Buján, Elba I; Argüello, Gustavo A

    2005-11-01

    The herbicide trifluralin (I)(N,N-di-n-propyl-2,6-dinitro-4-trifluoromethylaniline) decomposes, by the action of UV-Vis light (lambda > 300 nm), to several products, the most important (because they give subsequent photochemical reactions) being N-n-propyl-2,6-dinitro-4-trifluoromethylaniline (VI), 2-ethyl-7-nitro-5-trifluoromethyl-1H-benzimidazole 3-oxide (VII) and 2,6-dinitro-4-trifluoromethylaniline (XII). The time evolution of degradation of trifluralin (I) and the aforementioned three main photoproducts was studied in water and acetonitrile as solvents. The pseudo-first order rate constants allow one to calculate the branching ratios for some of the reactions involved. The preference for either N-dealkylation or cyclization depends on the solvent employed. Dissolved oxygen accelerates the photodegradation, especially the dealkylation.

  17. Biochemical and structural characterization of Klebsiella pneumoniae oxamate amidohydrolase in the uric acid degradation pathway

    Energy Technology Data Exchange (ETDEWEB)

    Hicks, Katherine A.; Ealick, Steven E.

    2016-05-25

    HpxW from the ubiquitous pathogenKlebsiella pneumoniaeis involved in a novel uric acid degradation pathway downstream from the formation of oxalurate. Specifically, HpxW is an oxamate amidohydrolase which catalyzes the conversion of oxamate to oxalate and is a member of the Ntn-hydrolase superfamily. HpxW is autoprocessed from an inactive precursor to form a heterodimer, resulting in a 35.5 kDa α subunit and a 20 kDa β subunit. Here, the structure of HpxW is presented and the substrate complex is modeled. In addition, the steady-state kinetics of this enzyme and two active-site variants were characterized. These structural and biochemical studies provide further insight into this class of enzymes and allow a mechanism for catalysis consistent with other members of the Ntn-hydrolase superfamily to be proposed.

  18. Trafficking and degradation pathways in pathogenic conversion of prions and prion-like proteins in neurodegenerative diseases.

    Science.gov (United States)

    Victoria, Guiliana Soraya; Zurzolo, Chiara

    2015-09-02

    Several neurodegenerative diseases such as transmissible spongiform encephalopathies, Alzheimer's and Parkinson's diseases are caused by the conversion of cellular proteins to a pathogenic conformer. Despite differences in the primary structure and subcellular localization of these proteins, which include the prion protein, α-synuclein and amyloid precursor protein (APP), striking similarity has been observed in their ability to seed and convert naïve protein molecules as well as transfer between cells. This review aims to cover what is known about the intracellular trafficking of these proteins as well as their degradation mechanisms and highlight similarities in their movement through the endocytic pathway that could contribute to the pathogenic conversion and seeding of these proteins which underlies the basis of these diseases.

  19. Lipid rafts participate in aberrant degradative autophagic-lysosomal pathway of amyloid-beta peptide in Alzheimer’s disease

    Institute of Scientific and Technical Information of China (English)

    Xin Zhou; Chun Yang; Yufeng Liu; Peng Li; Huiying Yang; Jingxing Dai; Rongmei Qu; Lin Yuan

    2014-01-01

    Amyloid-beta peptide is the main component of amyloid plaques, which are found in Alzhei-mer’s disease. The generation and deposition of amyloid-beta is one of the crucial factors for the onset and progression of Alzheimer’s disease. Lipid rafts are glycolipid-rich liquid domains of the plasma membrane, where certain types of protein tend to aggregate and intercalate. Lipid rafts are involved in the generation of amyloid-beta oligomers and the formation of amyloid-beta peptides. In this paper, we review the mechanism by which lipid rafts disturb the aberrant deg-radative autophagic-lysosomal pathway of amyloid-beta, which plays an important role in the pathological process of Alzheimer’s disease. Moreover, we describe this mechanism from the view of the Two-system Theory of fasciology and thus, suggest that lipid rafts may be a new target of Alzheimer’s disease treatment.

  20. Degradation Pathways for Geogenic Volatile Organic Compounds (VOCs) in Soil Gases from the Solfatara Crater (Campi Flegrei, Southern Italy).

    Science.gov (United States)

    Tassi, F.; Venturi, S.; Cabassi, J.; Capecchiacci, F.; Nisi, B., Sr.; Vaselli, O.

    2014-12-01

    The chemical composition of volatile organic compounds (VOCs) in soil gases from the Solfatara crater (Campi Flegrei, Southern Italy) was analyzed to investigate the effects of biogeochemical processes occurring within the crater soil on gases discharged from the hydrothermal reservoir and released into the atmosphere through diffuse degassing. In this system, two fumarolic vents (namely Bocca Grande and Bocca Nuova) are the preferential pathways for hydrothermal fluid uprising. For our goal, the chemistry of VOCs discharged from these sites were compared to that of soil gases. Our results highlighted that C4-C9 alkanes, alkenes, S-bearing compounds and alkylated aromatics produced at depth were the most prone to degradation processes, such as oxidation-reduction and hydration-dehydration reactions, as well as to microbial activity. Secondary products, which were enriched in sites characterized by low soil gas fluxes, mostly consisted of aldheydes, ketons, esters, ethers, organic acids and, subordinately, alcohols. Benzene, phenol and hydrofluorocarbons (HCFCs) produced at depth were able to transit through the soil almost undisturbed, independently on the emission rate of diffuse degassing. The presence of cyclics was possibly related to an independent low-temperature VOC source, likely within sedimentary formations overlying the hydrothermal reservoir. Chlorofluorocarbons (CFCs) were possibly due to air contamination. This study demonstrated the strict control of biogeochemical processes on the behaviour of hydrothermal VOCs that, at least at a local scale, may have a significant impact on air quality. Laboratory experiments conducted at specific chemical-physical conditions and in presence of different microbial populations may provide useful information for the reconstruction of the degradation pathways controlling fate and behaviour of VOCs in the soil.

  1. Key enzymes of the protocatechuate branch of the β-ketoadipate pathway for aromatic degradation in Corynebacterium glutamicum

    Institute of Scientific and Technical Information of China (English)

    SHEN; Xihui; LIU; Shuangjiang

    2005-01-01

    Although the protocatechuate branch of the β-ketoadipate pathway in Gram bacteria has been well studied, this branch is less understood in Gram+ bacteria. In this study,Corynebacterium glutamicum was cultivated with protocatechuate, p-cresol, vanillate and 4-hydroxybenzoate as sole carbon and energy sources for growth. Enzymatic assays indicated that growing cells on these aromatic compounds exhibited protocatechuate 3,4-dioxygenase activities. Data-mining of the genome of this bacterium revealed that the genetic locus ncg12314-ncg12315 encoded a putative protocatechuate 3,4-dioxygenase. The genes,ncg12314 and ncg12315, were amplified by PCR technique and were cloned into plasmid (pET21aP34D). Recombinant Escherichia coli strain harboring this plasmid actively expressed protocatechuate 3,4-dioxygenase activity. Further, when this locus was disrupted in C. glutamicum, the ability to degrade and assimilate protocatechuate, p-cresol, vanillate or 4-hydroxybenzoate was lost and protocatechuate 3,4-dioxygenase activity was disappeared. The ability to grow with these aromatic compounds and protocatechuate 3,4-dioxygenase activity of C.glutamicum mutant could be restored by gene complementation. Thus, it is clear that the key enzyme for ring-cleavage, protocatechuate 3,4-dioxygenase, was encoded by ncg12314 and ncg12315. The additional genes involved in the protocatechuate branch of the β-ketoadipate pathway were identified by mining the genome data publically available in the GenBank. The functional identification of genes and their unique organization in C. glutamicum provided new insight into the genetic diversity of aromatic compound degradation.

  2. Oncogenic activation of the Met receptor tyrosine kinase fusion protein, Tpr-Met, involves exclusion from the endocytic degradative pathway.

    Science.gov (United States)

    Mak, H H L; Peschard, P; Lin, T; Naujokas, M A; Zuo, D; Park, M

    2007-11-01

    Multiple mechanisms of dysregulation of receptor tyrosine kinases (RTKs) are observed in human cancers. In addition to gain-of-function, loss of negative regulation also contributes to oncogenic activation of RTKs. Negative regulation of many RTKs involves their internalization and degradation in the lysosome, a process regulated through ubiquitination. RTK oncoproteins activated following chromosomal translocation, are no longer transmembrane proteins, and are predicted to escape lysosomal degradation. To test this, we used the Tpr-Met oncogene, generated following chromosomal translocation of the hepatocyte growth factor receptor (Met). Unlike Met, Tpr-Met is localized in the cytoplasm and also lacks the binding site for Cbl ubiquitin ligases. We determined whether subcellular localization of Tpr-Met, and/or loss of its Cbl-binding site, is important for oncogenic activity. Presence of a Cbl-binding site and ubiquitination of cytosolic Tpr-Met oncoproteins does not alter their transforming activity. In contrast, plasma membrane targeting allows Tpr-Met to enter the endocytic pathway, and Tpr-Met transforming activity as well as protein stability are decreased in a Cbl-dependent manner. We show that transformation by Tpr-Met is in part dependent on its ability to escape normal downregulatory mechanisms. This provides a paradigm for many RTK oncoproteins activated following chromosomal translocation.

  3. Biochemical, transcriptional and translational evidences of the phenol-meta-degradation pathway by the hyperthermophilic Sulfolobus solfataricus 98/2.

    Directory of Open Access Journals (Sweden)

    Alexia Comte

    Full Text Available Phenol is a widespread pollutant and a model molecule to study the biodegradation of monoaromatic compounds. After a first oxidation step leading to catechol in mesophilic and thermophilic microorganisms, two main routes have been identified depending on the cleavage of the aromatic ring: ortho involving a catechol 1,2 dioxygenase (C12D and meta involving a catechol 2,3 dioxygenase (C23D. Our work aimed at elucidating the phenol-degradation pathway in the hyperthermophilic archaea Sulfolobus solfataricus 98/2. For this purpose, the strain was cultivated in a fermentor under different substrate and oxygenation conditions. Indeed, reducing dissolved-oxygen concentration allowed slowing down phenol catabolism (specific growth and phenol-consumption rates dropped 55% and 39%, respectively and thus, evidencing intermediate accumulations in the broth. HPLC/Diode Array Detector and LC-MS analyses on culture samples at low dissolved-oxygen concentration (DOC  =  0.06 mg x L(-1 suggested, apart for catechol, the presence of 2-hydroxymuconic acid, 4-oxalocrotonate and 4-hydroxy-2-oxovalerate, three intermediates of the meta route. RT-PCR analysis on oxygenase-coding genes of S. solfataricus 98/2 showed that the gene coding for the C23D was expressed only on phenol. In 2D-DIGE/MALDI-TOF analysis, the C23D was found and identified only on phenol. This set of results allowed us concluding that S. solfataricus 98/2 degrade phenol through the meta route.

  4. Relative Contribution of Prolyl Hydroxylase-Dependent and -Independent Degradation of HIF-1alpha by Proteasomal Pathways in Cerebral Ischemia

    Directory of Open Access Journals (Sweden)

    Yomna Badawi

    2017-05-01

    Full Text Available Hypoxia inducible factor-1 (HIF-1 is a key regulator in hypoxia and can determine the fate of brain cells during ischemia. However, the mechanism of HIF-1 regulation is still not fully understood in ischemic brains. We tested a hypothesis that both the 26S and the 20S proteasomal pathways were involved in HIF-1α degradation under ischemic conditions. Using in vitro ischemic model (oxygen and glucose deprivation and a mouse model of middle cerebral artery occlusion, we tested effects of inhibitors of proteasomes and prolyl hydroxylase (PHD on HIF-1α stability and brain injury in cerebral ischemia. We observed that 30 and 60 min of oxygen-glucose deprivation significantly increased the 20S proteasomal activity. We demonstrated that proteasome inhibitors increased HIF-1α stabilization and cell viability and were more effective than PHD inhibitors in primary cultured cortical neurons exposed to oxygen and glucose deprivation. Furthermore, the administration of the proteasome inhibitor, epoxomicin, to mice resulted in smaller infarct size and brain edema than a PHD inhibitor. Our results indicate that 20S proteasomes are involved in HIF-1α degradation in ischemic neurons and that proteasomal inhibition provides more HIF-1α stabilization and neuroprotection than PHD inhibition in cerebral ischemia.

  5. Sources and Input Pathways of Glyphosate and its Degradation Product AMPA

    Science.gov (United States)

    Bischofberger, S.; Hanke, I.; Wittmer, I.; Singer, H.; Stamm, C.

    2009-04-01

    Despite being the pesticide used in the largest quantities worldwide, the environmental relevance of glyphosate has been considered low for many years. Reasons for this assessment were the observations that glyphosate degrades quickly into its degradation product AMPA and that it sorbs strongly to soil particles. Hence, little losses to water bodies had been expected. Research during the last few years however contradicts this expectation. Although glyphosate is a dominant pesticide used in agriculture, recent studies on other pesticides revealed that urban sources may play a significant role for water quality. Therefore this study compares glyphosate input into streams from agricultural and urban sources. For that purpose, a catchment of an area of 25 km2 was selected. It has by about 12'000 inhabitants and about 15 % of the area is used as arable land. Four sampling sites were selected in the river system in order to reflect different urban and agricultural sources. Additionally, we sampled a combined sewer overflow, a rain sewer and the outflow of a waste water treatment plant. At each site discharge was measured continuously from March to November 2007. During 16 rain events samples were taken by automatic devices at a high temporal resolution. To analyze the concentration of glyphosate and its degradation product AMPA, the samples were derivatized with FMOC-Cl at low pH conditions and then filtrated. The solid phase extraction was conducted with Strata-X sorbent cartridge. Glyphosate and AMPA were detected with API 4000 after the chromatography with X bridge column C18. To assure the data quality, interne standards of Glyphosate and AMPA were added to every sample. The limit of detection and quantification for glyphosate and AMPA are bellow 1ng/l. We analyzed two rain events at a high resolution for all stations and several events at the outlet of the catchment. We measured high glyphosate concentration in urban and agriculture dominated catchments with up to

  6. Abatement and degradation pathways of toluene in indoor air by positive corona discharge.

    Science.gov (United States)

    Van Durme, J; Dewulf, J; Sysmans, W; Leys, C; Van Langenhove, H

    2007-08-01

    Indoor air concentrations of volatile organic compounds often exceed outdoor levels by a factor of 5. There is much interest in developing new technologies in order to improve indoor air quality. In this work non-thermal plasma (DC positive corona discharge) is explored as an innovative technology for indoor air purification. An inlet gas stream of 10 l min(-1) containing 0.50+/-0.02 ppm toluene was treated by the plasma reactor in atmospheric conditions. Toluene removal proved to be achievable with a characteristic energy density epsilon(0) of 50 J l(-1). Removal efficiencies were higher for 26% relative humidity (epsilon(0)=35 J l(-1)), compared with those at increased humidities (50% relative humidity, epsilon(0)=49 J l(-1)). Reaction products such as formic acid, benzaldehyde, benzyl alcohol, 3-methyl-4-nitrophenol, 4-methyl-2-nitrophenol, 4-methyl-2-propyl furan, 5-methyl-2-nitrophenol, 4-nitrophenol, 2-methyl-4,6-dinitrophenol are identified by means of mass spectrometry. Based on these by-products a toluene degradation mechanism is proposed.

  7. Microbial oil-degradation under mild hydrostatic pressure (10 MPa): which pathways are impacted in piezosensitive hydrocarbonoclastic bacteria?

    Science.gov (United States)

    Scoma, Alberto; Barbato, Marta; Hernandez-Sanabria, Emma; Mapelli, Francesca; Daffonchio, Daniele; Borin, Sara; Boon, Nico

    2016-03-01

    Oil spills represent an overwhelming carbon input to the marine environment that immediately impacts the sea surface ecosystem. Microbial communities degrading the oil fraction that eventually sinks to the seafloor must also deal with hydrostatic pressure, which linearly increases with depth. Piezosensitive hydrocarbonoclastic bacteria are ideal candidates to elucidate impaired pathways following oil spills at low depth. In the present paper, we tested two strains of the ubiquitous Alcanivorax genus, namely A. jadensis KS_339 and A. dieselolei KS_293, which is known to rapidly grow after oil spills. Strains were subjected to atmospheric and mild pressure (0.1, 5 and 10 MPa, corresponding to a depth of 0, 500 and 1000 m, respectively) providing n-dodecane as sole carbon source. Pressures equal to 5 and 10 MPa significantly lowered growth yields of both strains. However, in strain KS_293 grown at 10 MPa CO2 production per cell was not affected, cell integrity was preserved and PO43- uptake increased. Analysis of its transcriptome revealed that 95% of its genes were downregulated. Increased transcription involved protein synthesis, energy generation and respiration pathways. Interplay between these factors may play a key role in shaping the structure of microbial communities developed after oil spills at low depth and limit their bioremediation potential.

  8. Microbial oil-degradation under mild hydrostatic pressure (10 MPa): which pathways are impacted in piezosensitive hydrocarbonoclastic bacteria?

    KAUST Repository

    Scoma, Alberto

    2016-03-29

    Oil spills represent an overwhelming carbon input to the marine environment that immediately impacts the sea surface ecosystem. Microbial communities degrading the oil fraction that eventually sinks to the seafloor must also deal with hydrostatic pressure, which linearly increases with depth. Piezosensitive hydrocarbonoclastic bacteria are ideal candidates to elucidate impaired pathways following oil spills at low depth. In the present paper, we tested two strains of the ubiquitous Alcanivorax genus, namely A. jadensis KS_339 and A. dieselolei KS_293, which is known to rapidly grow after oil spills. Strains were subjected to atmospheric and mild pressure (0.1, 5 and 10 MPa, corresponding to a depth of 0, 500 and 1000 m, respectively) providing n-dodecane as sole carbon source. Pressures equal to 5 and 10 MPa significantly lowered growth yields of both strains. However, in strain KS_293 grown at 10 MPa CO2 production per cell was not affected, cell integrity was preserved and PO43− uptake increased. Analysis of its transcriptome revealed that 95% of its genes were downregulated. Increased transcription involved protein synthesis, energy generation and respiration pathways. Interplay between these factors may play a key role in shaping the structure of microbial communities developed after oil spills at low depth and limit their bioremediation potential.

  9. Sulfoacetate is degraded via a novel pathway involving sulfoacetyl-CoA and sulfoacetaldehyde in Cupriavidus necator H16.

    Science.gov (United States)

    Weinitschke, Sonja; Hollemeyer, Klaus; Kusian, Bernhard; Bowien, Botho; Smits, Theo H M; Cook, Alasdair M

    2010-11-12

    Bacterial degradation of sulfoacetate, a widespread natural product, proceeds via sulfoacetaldehyde and requires a considerable initial energy input. Whereas the fate of sulfoacetaldehyde in Cupriavidus necator (Ralstonia eutropha) H16 is known, the pathway from sulfoacetate to sulfoacetaldehyde is not. The genome sequence of the organism enabled us to hypothesize that the inducible pathway, which initiates sau (sulfoacetate utilization), involved a four-gene cluster (sauRSTU; H16_A2746 to H16_A2749). The sauR gene, divergently orientated to the other three genes, probably encodes the transcriptional regulator of the presumed sauSTU operon, which is subject to inducible transcription. SauU was tentatively identified as a transporter of the major facilitator superfamily, and SauT was deduced to be a sulfoacetate-CoA ligase. SauT was a labile protein, but it could be separated and shown to generate AMP and an unknown, labile CoA-derivative from sulfoacetate, CoA, and ATP. This unknown compound, analyzed by MALDI-TOF-MS, had a relative molecular mass of 889.7, which identified it as protonated sulfoacetyl-CoA (calculated 889.6). SauS was deduced to be sulfoacetaldehyde dehydrogenase (acylating). The enzyme was purified 175-fold to homogeneity and characterized. Peptide mass fingerprinting confirmed the sauS locus (H16_A2747). SauS converted sulfoacetyl-CoA and NADPH to sulfoacetaldehyde, CoA, and NADP(+), thus confirming the hypothesis.

  10. [Polio vaccines, eradication and posterradication].

    Science.gov (United States)

    Salmerón García, Francisco; Portela Moreira, Agustín; Soler Soneira, Marta; López Hernández, Susana; Chamorro Somoza Díaz-Sarmiento, María; Pérez González, Isabel; Rubio Gómez, María Isabel; Pérez González, Alicia; Sagredo Rodríguez, Ana; Ruiz Antúnez, Sol; Timón Jiménez, Marcos; Frutos Cabanillas, Gloria

    2013-01-01

    Vaccination against polio generates herd immunity (both with the attenuated (OPV) and inactivated (IPV) vaccines) and this will allow the eradication of the disease. The OPV vaccine produces 2-4 polio cases per cohort of one million children and therefore IPV is used in countries that can afford its cost (about 15 times more expensive than OPV). In 1988 the World Health Assembly established the polio eradication goal as "interruption of wild poliovirus transmission". If the elimination of wild poliovirus were achieved, the use of OPV will produce annually between 250 and 500 cases of polio in the world. From 1999, it was clear that eradication would require ending of immunization with OPV. On the 25th of January, 2013 it is approved the plan for the eradication and containment of all polioviruses, wild or not, so that no child suffers paralytic poliomyelitis. The most important landmarks include the lack of wild polio cases after 2014, the introduction of at least one dose of IPV in all immunization programs and to cease the type 2 OPV vaccination by the end of 2016 and to stop the use of the oral bivalent vaccine in 2019. To achieve all this, a complex scientific work and economic solidarity will be required.

  11. Urothelial endocytic vesicle recycling and lysosomal degradative pathway regulated by lipid membrane composition.

    Science.gov (United States)

    Grasso, E J; Calderón, R O

    2013-02-01

    The urothelium, a specialized epithelium that covers the mucosa cell surface of the urinary bladder, undergoes dramatic morphological changes during the micturition cycle that involve a membrane apical traffic. This traffic was first described as a lysosomal pathway, in addition to the known endocytosis/exocytosis membrane recycling. In an attempt to understand the role of membrane lipid composition in those effects, we previously described the lipid-dependent leakage of the endocytosed vesicle content. In this work, we demonstrated clear differences in the traffic of both the fluid probe and the membrane-bound probe in urothelial umbrella cells by using spectrofluorometry and/or confocal and epifluorescence microscopy. Different membrane lipid compositions were established by using three diet formulae enriched in oleic acid, linoleic acid and a commercial formula. Between three and five animals for each dietary treatment were used for each analysis. The decreased endocytosis of both fluid and membrane-bound probes (approximately 32 and 49 % lower, respectively) in oleic acid-derived umbrella cells was concomitant with an increased recycling (approximately 4.0 and 3.7 times, respectively) and diminished sorting to the lysosome (approximately 23 and 37 %, respectively) when compared with the control umbrella cells. The higher intravesicular pH and the impairment of the lysosomal pathway of oleic acid diet-derived vesicles compared to linoleic acid diet-derived vesicles and control diet-derived vesicles correlate with our findings of a lower V-ATPase activity previously reported. We integrated the results obtained in the present and previous work to determine the sorting of endocytosed material (fluid and membrane-bound probes) into the different cell compartments. Finally, the weighted average effect of the individual alterations on the intracellular distribution was evaluated. The results shown in this work add evidences for the modulatory role of the membrane

  12. Cx31 is assembled and trafficked to cell surface by ER-Golgi pathway and degraded by proteasomal or lysosomal pathways

    Institute of Scientific and Technical Information of China (English)

    Li Qiang HE; Zhi Gao LONG; He Ping DAI; Kun XIA; Jia Hui XIA; Zhuo Hua ZHANG; Fang CAI; Yu LIU; Mu Jun LIU; Zhi Ping TAN; Qian PAN; Fai Yan FANG; De Sheng LIANG; Ling Qian WU

    2005-01-01

    Gap junctions, consisting of connexins, allow the exchange of small molecules (<1 kD) between adjacent cells, thus providing a mechanism for synchronizing the responses of groups of cells to environmental stimuli. Connexin 31 is a member of the connexin family. Mutations on connexin 31 are associated with erythrokeratodermia variabilis, hearing impairment and peripheral neuropathy. However, the pathological mechanism for connexin 31 mutants in these diseases are still unknown. In this study, we analyzed the assembly, trafficking and metabolism of connexin 31 in HeLa cells stably expressing connexin 31. Calcein transfer assay showed that calcein transfer was inhibited when cells were treated with Brefeldin A or cytochalasin D, but not when treated with nocodazole or α-glycyrrhetinic acid, suggesting that Golgi apparatus and actin filaments, but not microtubules, are crucial to the trafficking and assembly of connexin 31, as well as the formation of gap junction intercellular communication by connexin 31. Additionally, α-glycyrrhetinic acid did not effectively inhibit gap junctional intercellular communication formed by connexin 31. Pulse-chase assay revealed that connexin 31 had a half-life of about 6 h. Moreover, Western blotting and fluorescent staining demonstrated that in HeLa cells stably expressing connexin 31, the amount of connexin 31 was significantly increased after these cells were treated with proteasomal or lysosomal inhibitors. These findings indicate that connexin 31 was rapidly renewed,and possibly degraded by both proteasomal and lysosomal pathways.

  13. Streptococcus pyogenes malate degradation pathway links pH regulation and virulence.

    Science.gov (United States)

    Paluscio, Elyse; Caparon, Michael G

    2015-03-01

    The ability of Streptococcus pyogenes to infect different niches within its human host most likely relies on its ability to utilize alternative carbon sources. In examining this question, we discovered that all sequenced S. pyogenes strains possess the genes for the malic enzyme (ME) pathway, which allows malate to be used as a supplemental carbon source for growth. ME is comprised of four genes in two adjacent operons, with the regulatory two-component MaeKR required for expression of genes encoding a malate permease (maeP) and malic enzyme (maeE). Analysis of transcription indicated that expression of maeP and maeE is induced by both malate and low pH, and induction in response to both cues is dependent on the MaeK sensor kinase. Furthermore, both maePE and maeKR are repressed by glucose, which occurs via a CcpA-independent mechanism. Additionally, malate utilization requires the PTS transporter EI enzyme (PtsI), as a PtsI(-) mutant fails to express the ME genes and is unable to utilize malate. Virulence of selected ME mutants was assessed in a murine model of soft tissue infection. MaeP(-), MaeK(-), and MaeR(-) mutants were attenuated for virulence, whereas a MaeE(-) mutant showed enhanced virulence compared to that of the wild type. Taken together, these data show that ME contributes to S. pyogenes' carbon source repertory, that malate utilization is a highly regulated process, and that a single regulator controls ME expression in response to diverse signals. Furthermore, malate uptake and utilization contribute to the adaptive pH response, and ME can influence the outcome of infection.

  14. Degradation of {gamma}-HCH spiked soil using stabilized Pd/Fe{sup 0} bimetallic nanoparticles: Pathways, kinetics and effect of reaction conditions

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Ritu [Ecotoxicology Division, CSIR-Indian Institute of Toxicology Research, Post Box 80, Mahatma Gandhi Marg, Lucknow 226 001, UP (India); Department of Environmental Science, Babasaheb Bhimrao Ambedkar University, Raebareli Road, Lucknow 226 025, UP (India); Misra, Virendra, E-mail: virendra_misra2001@yahoo.co.in [Ecotoxicology Division, CSIR-Indian Institute of Toxicology Research, Post Box 80, Mahatma Gandhi Marg, Lucknow 226 001, UP (India); Mudiam, Mohana Krishna Reddy [Analytical Chemistry Division, CSIR-Indian Institute of Toxicology Research, Post Box 80, Mahatma Gandhi Marg, Lucknow 226 001, UP (India); Chauhan, Lalit Kumar Singh [Petroleum Toxicology Division, CSIR-Indian Institute of Toxicology Research, Post Box 80, Mahatma Gandhi Marg, Lucknow 226 001, UP (India); Singh, Rana Pratap [Department of Environmental Science, Babasaheb Bhimrao Ambedkar University, Raebareli Road, Lucknow 226 025, UP (India)

    2012-10-30

    Highlights: Black-Right-Pointing-Pointer This study explores the potential of CMC-Pd/nFe{sup 0} to degrade {gamma}-HCH in spiked soil. Black-Right-Pointing-Pointer Sorption-desorption characteristics and partitioning of {gamma}-HCH is investigated. Black-Right-Pointing-Pointer Three degradation pathways has been proposed and discussed. Black-Right-Pointing-Pointer {gamma}-HCH degradation mechanism and kinetics is elucidated. Black-Right-Pointing-Pointer Activation energy reveals that {gamma}-HCH degradation is a surface mediated reaction. - Abstract: This study investigates the degradation pathway of gamma-hexachlorocyclohexane ({gamma}-HCH) in spiked soil using carboxymethyl cellulose stabilized Pd/Fe{sup 0} bimetallic nanoparticles (CMC-Pd/nFe{sup 0}). GC-MS analysis of {gamma}-HCH degradation products showed the formation of pentachlorocyclohexene, tri- and di-chlorobenzene as intermediate products while benzene was formed as the most stable end product. On the basis of identified intermediates and final products, degradation pathway of {gamma}-HCH has been proposed. Batch studies showed complete {gamma}-HCH degradation at a loading of 0.20 g/L CMC-Pd/nFe{sup 0} within 6 h of incubation. The surface area normalized rate constant (k{sub SA}) was found to be 7.6 Multiplication-Sign 10{sup -2} L min{sup -1} m{sup -2}. CMC-Pd/nFe{sup 0} displayed {approx}7-fold greater efficiency for {gamma}-HCH degradation in comparison to Fe{sup 0} nanoparticles (nFe{sup 0}), synthesized without CMC and Pd. Further studies showed that increase in CMC-Pd/nFe{sup 0} loading and reaction temperature facilitates {gamma}-HCH degradation, whereas a declining trend in degradation was noticed with the increase in pH, initial {gamma}-HCH concentration and in the presence of cations. The data on activation energy (33.7 kJ/mol) suggests that {gamma}-HCH degradation is a surface mediated reaction. The significance of the study with respect to remediation of {gamma}-HCH contaminated soil using

  15. Metagenomic Analysis of Hot Springs in Central India Reveals Hydrocarbon Degrading Thermophiles and Pathways Essential for Survival in Extreme Environments

    Science.gov (United States)

    Saxena, Rituja; Dhakan, Darshan B.; Mittal, Parul; Waiker, Prashant; Chowdhury, Anirban; Ghatak, Arundhuti; Sharma, Vineet K.

    2017-01-01

    Extreme ecosystems such as hot springs are of great interest as a source of novel extremophilic species, enzymes, metabolic functions for survival and biotechnological products. India harbors hundreds of hot springs, the majority of which are not yet explored and require comprehensive studies to unravel their unknown and untapped phylogenetic and functional diversity. The aim of this study was to perform a large-scale metagenomic analysis of three major hot springs located in central India namely, Badi Anhoni, Chhoti Anhoni, and Tattapani at two geographically distinct regions (Anhoni and Tattapani), to uncover the resident microbial community and their metabolic traits. Samples were collected from seven distinct sites of the three hot spring locations with temperature ranging from 43.5 to 98°C. The 16S rRNA gene amplicon sequencing of V3 hypervariable region and shotgun metagenome sequencing uncovered a unique taxonomic and metabolic diversity of the resident thermophilic microbial community in these hot springs. Genes associated with hydrocarbon degradation pathways, such as benzoate, xylene, toluene, and benzene were observed to be abundant in the Anhoni hot springs (43.5–55°C), dominated by Pseudomonas stutzeri and Acidovorax sp., suggesting the presence of chemoorganotrophic thermophilic community with the ability to utilize complex hydrocarbons as a source of energy. A high abundance of genes belonging to methane metabolism pathway was observed at Chhoti Anhoni hot spring, where methane is reported to constitute >80% of all the emitted gases, which was marked by the high abundance of Methylococcus capsulatus. The Tattapani hot spring, with a high-temperature range (61.5–98°C), displayed a lower microbial diversity and was primarily dominated by a nitrate-reducing archaeal species Pyrobaculum aerophilum. A higher abundance of cell metabolism pathways essential for the microbial survival in extreme conditions was observed at Tattapani. Taken together

  16. Aqueous photochemical degradation of hydroxylated PAHs: Kinetics, pathways, and multivariate effects of main water constituents

    Energy Technology Data Exchange (ETDEWEB)

    Ge, Linke; Na, Guangshui [Key Laboratory for Ecological Environment in Coastal Areas (SOA), National Marine Environmental Monitoring Center, Dalian 116023 (China); Chen, Chang-Er [Lancaster Environment Centre, Lancaster University, Lancaster LA1 4YQ (United Kingdom); Li, Jun [Key Laboratory for Ecological Environment in Coastal Areas (SOA), National Marine Environmental Monitoring Center, Dalian 116023 (China); College of Marine Science, Shanghai Ocean University, Shanghai 201306 (China); Ju, Maowei; Wang, Ying; Li, Kai [Key Laboratory for Ecological Environment in Coastal Areas (SOA), National Marine Environmental Monitoring Center, Dalian 116023 (China); Zhang, Peng, E-mail: pzhang@nmemc.org.cn [Key Laboratory for Ecological Environment in Coastal Areas (SOA), National Marine Environmental Monitoring Center, Dalian 116023 (China); Yao, Ziwei [Key Laboratory for Ecological Environment in Coastal Areas (SOA), National Marine Environmental Monitoring Center, Dalian 116023 (China)

    2016-03-15

    PAHs. • Hydroxylated PAHs intrinsically photodegrade fast in sunlit surface waters. • Reaction types and transformation pathways of 9-Hydroxyfluorene were clarified. • Photolysis kinetics was affected by multivariate effects of main water constituents. • The photomodified toxicity of 9-Hydroxyfluorene was examined using Vibrio fischeri.

  17. Isolation of Alcaligenes sp strain L6 at low oxygen concentrations and degradation of 3-chlorobenzoate via a pathway not involving (chloro)catechols

    NARCIS (Netherlands)

    Krooneman, J; Wieringa, EBA; Moore, ERB; Gerritse, J; Prins, RA; Gottschal, JC

    1996-01-01

    Isolations of 3-chlorobenzoate (3CBA)-degrading aerobic bacteria under reduced O-2, partial pressures yielded organisms which metabolized 3CBA via the gentisate or the protocatechuate pathway rather than via the catechol route. The 3CBA metabolism of one of these isolates, L6, which,vas identified a

  18. Poliomyelitis eradication: Rhetoric or reality

    Science.gov (United States)

    Bhatnagar, Nidhi; Grover, Manoj; Sinha, Smita; Kaur, Ravneet

    2013-01-01

    Since the launch of Global Polio Eradication Initiative in 1988, disease burden has been reduced by more than 99% globally. Lately, India has witnessed a year without a case of poliomyelitis. It no longer stands endemic and is being regarded as a model for polio eradication efforts in other low income endemic countries: Pakistan, Nigeria and Afghanistan. The near elimination of wild polio virus in India has set forth new challenges of vaccine derived polio virus and need for newer strategies in oral poliomyelitis vaccine cessation preparatory phase. Stricter surveillance measures are needed to check for importations, any spread of virus in migratory populations and rapid containment of newly found virus. No stone should be left unturned in this last ditch effort for extermination of polio virus form environmental circulation. India's battle against polio will be cited as the biggest public health achievement or the most expensive public health failure.

  19. Dysregulation of protein degradation pathways may mediate the liver injury and phospholipidosis associated with a cationic amphiphilic antibiotic drug

    Energy Technology Data Exchange (ETDEWEB)

    Mosedale, Merrie [Hamner-University of North Carolina Institute for Drug Safety Sciences, The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709 (United States); Wu, Hong [Drug Safety Research and Development, Pfizer Global Research and Development, Groton, CT06340 (United States); Kurtz, C. Lisa [Hamner-University of North Carolina Institute for Drug Safety Sciences, The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709 (United States); Schmidt, Stephen P. [Drug Safety Research and Development, Pfizer Global Research and Development, Groton, CT06340 (United States); Adkins, Karissa, E-mail: Karissa.Adkins@pfizer.com [Drug Safety Research and Development, Pfizer Global Research and Development, Groton, CT06340 (United States); Harrill, Alison H. [Hamner-University of North Carolina Institute for Drug Safety Sciences, The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709 (United States); University of Arkansas for Medical Sciences, Little Rock, AR72205 (United States)

    2014-10-01

    A large number of antibiotics are known to cause drug-induced liver injury in the clinic; however, interpreting clinical risk is not straightforward owing to a lack of predictivity of the toxicity by standard preclinical species and a poor understanding of the mechanisms of toxicity. An example is PF-04287881, a novel ketolide antibiotic that caused elevations in liver function tests in Phase I clinical studies. In this study, a mouse diversity panel (MDP), comprised of 34 genetically diverse, inbred mouse strains, was utilized to model the toxicity observed with PF-04287881 treatment and investigate potential mechanisms that may mediate the liver response. Significant elevations in serum alanine aminotransferase (ALT) levels in PF-04287881-treated animals relative to vehicle-treated controls were observed in the majority (88%) of strains tested following a seven day exposure. The average fold elevation in ALT varied by genetic background and correlated with microscopic findings of hepatocellular hypertrophy, hepatocellular single cell necrosis, and Kupffer cell vacuolation (confirmed as phospholipidosis) in the liver. Global liver mRNA expression was evaluated in a subset of four strains to identify transcript and pathway differences that distinguish susceptible mice from resistant mice in the context of PF-04287881 treatment. The protein ubiquitination pathway was highly enriched among genes associated with PF-04287881-induced hepatocellular necrosis. Expression changes associated with PF-04287881-induced phospholipidosis included genes involved in drug transport, phospholipid metabolism, and lysosomal function. The findings suggest that perturbations in genes involved in protein degradation leading to accumulation of oxidized proteins may mediate the liver injury induced by this drug. - Highlights: • Identified susceptible and resistant mouse strains to liver injury induced by a CAD • Liver injury characterized by single cell necrosis, and phospholipidosis

  20. Experimental Priapism is Associated with Increased Oxidative Stress and Activation of Protein Degradation Pathways in Corporal Tissue

    Science.gov (United States)

    Kanika, Nirmala D.; Melman, Arnold; Davies, Kelvin P.

    2010-01-01

    Priapism is a debilitating disease for which there is at present no clinically accepted pharmacologic intervention. It has been estimated that priapism lasting more than 24 hours in patients is associated with a 44–90% rate of erectile dysfunction (ED). In this investigation we determined in two animal models of priapism (opiorpin-induced priapism in the rat and priapism in a mouse model of sickle cell disease) if there is evidence for an increase in markers of oxidative stress in corporal tissue. In both animal models we demonstrate that priapism results in increased levels of lipid peroxidation, glutathione S-transferase activity, and oxidatively damaged proteins in corporal tissue. Using Western blot analysis we demonstrated there is up regulation of the ubiquitination ligase proteins, Nedd-4 and Mdm-2, and the lysososomal autophage protein, LC3. The anti-apoptotic protein, Bcl-2, was also up regulated. Overall, we demonstrate that priapism is associated with increased oxidative stress in corporal tissue and the activation of protein degradation pathways. Since oxidative stress is known to mediate the development of ED resulting from several etiologies (for example ED resulting from diabetes and aging) we suggest that damage to erectile tissue resulting from priapism might be prevented by treatments targeting oxidative stress. PMID:21085184

  1. Effects of rapid or slow body weight reduction on intramuscular protein degradation pathways during equivalent weight loss on rats.

    Science.gov (United States)

    Nonaka, Y; Urashima, S; Inai, M; Nishimura, S; Higashida, K; Terada, S

    2017-07-18

    The purpose of this study was to compare the effects of short-term fasting-induced rapid weight loss with those of slower but equivalent body weight loss induced by daily calorie restriction on muscle protein degradation pathways and muscle protein content. Male Fischer rats were subjected to either 30 % calorie restriction for 2 weeks to slowly decrease body weight (Slow) or 3-day fasting to rapidly decrease body weight by a comparable level of that of the Slow group (Rapid). The final body weights were about 15 % lower in both the Slow and Rapid groups than in the Con group (pweight of fast-twitch plantaris muscle, but not slow-twitch soleus muscle, were significantly lower in the Rapid group compared with the control rats fed ad libitum. Substantial increases in the expression ratio of autophagosomal membrane proteins (LC3-II/-I ratio) and polyubiquitinated protein concentration, used as biomarkers of autophagy-lysosome and ubiquitin-proteasome activities, respectively, were observed in the plantaris muscle of the Rapid group. Moreover, the LC3-II/-I ratio and polyubiquitinated protein concentration were negatively correlated with the total protein content and wet weight of plantaris muscle. These results suggest that short-term fasting-induced rapid body weight loss activates autophagy-lysosome and ubiquitin-proteasome systems more strongly than calorie restriction-induced slower weight reduction, resulting in muscular atrophy in fast-twitch muscle.

  2. RINL, guanine nucleotide exchange factor Rab5-subfamily, is involved in the EphA8-degradation pathway with odin.

    Directory of Open Access Journals (Sweden)

    Hiroaki Kajiho

    Full Text Available The Rab family of small guanosine triphosphatases (GTPases plays a vital role in membrane trafficking. Its active GTP-bound state is driven by guanine nucleotide-exchange factors (GEFs. Ras and Rab interactor (or Ras interaction/interference-like (RINL, which contains a conserved VPS9 domain critical for GEF action, was recently identified as a new Rab5 subfamily GEF in vitro. However, its detailed function and interacting molecules have not yet been fully elucidated. Here we found that RINL has GEF activity for the Rab5 subfamily proteins by measuring their GTP-bound forms in cultured cells. We also found that RINL interacts with odin, a member of the ankyrin-repeat and sterile-alpha motif (SAM domain-containing (Anks protein family. In addition, the Eph tyrosine kinase receptor EphA8 formed a ternary complex with both RINL and odin. Interestingly, RINL expression in cultured cells reduced EphA8 levels in a manner dependent on both its GEF activity and interaction with odin. In addition, knockdown of RINL increased EphA8 level in HeLa cells. Our findings suggest that RINL, as a GEF for Rab5 subfamily, is implicated in the EphA8-degradation pathway via its interaction with odin.

  3. Degradation of ethyl paraben by heat-activated persulfate oxidation: statistical evaluation of operating factors and transformation pathways.

    Science.gov (United States)

    Frontistis, Zacharias; Antonopoulou, Maria; Konstantinou, Ioannis; Mantzavinos, Dionissios

    2017-01-01

    A factorial design methodology was implemented to evaluate the importance of ethyl paraben (EP) concentration (500-1500 μg/L), sodium persulfate concentration (400-500 mg/L), temperature (40-60 °C), reaction time (2-30 min), water matrix (pure water or secondary treated wastewater), and initial solution pH (3-9) on EP removal by heat-activated persulfate oxidation. All individual effects, except the solution pH, were statistically significant and so were the second-order interactions of ethyl paraben concentration with temperature or the reaction time. The influence of the water matrix was crucial, and the efficiency of the process was lower in secondary treated wastewater due to the presence of natural organic matter and inorganic salts that compete with ethyl paraben for the reactive oxygen species. Liquid chromatography time-of-flight mass spectrometry (LC-TOF-MS) was employed to identify major transformation by-products (TBPs); 13 compounds were detected as TBPs of EP. Degradation occurred through (i) hydroxylation, (ii) dealkylation, and (iii) oligomerization reactions leading to TBPs with ether and biphenyl structures. Oligomerization reactions were found to be the dominant pathway during the first steps of the reaction. The toxicity of 500 μg/L EP in secondary treated wastewater was tested against marine bacteria Vibrio fischeri; toxicity increased during the first minutes due to the production of several TBPs, but it consistently decreased thereafter.

  4. EDEM2 and OS-9 are required for ER-associated degradation of non-glycosylated sonic hedgehog.

    Directory of Open Access Journals (Sweden)

    Hsiang-Yun Tang

    Full Text Available Misfolded proteins of the endoplasmic reticulum (ER are eliminated by the ER-associated degradation (ERAD in eukaryotes. In S. cerevisiae, ER-resident lectins mediate substrate recognition through bipartite signals consisting of an unfolded local structure and the adjacent glycan. Trimming of the glycan is essential for the directional delivery of the substrates. Whether a similar recognition and delivery mechanism exists in mammalian cells is unknown. In this study, we systematically study the function and substrate specificity of known mammalian ER lectins, including EDEM1/2/3, OS-9 and XTP-3B using the recently identified ERAD substrate sonic hedgehog (SHH, a soluble protein carrying a single N-glycan, as well as its nonglycosylated mutant N278A. Efficient ERAD of N278A requires the core processing complex of HRD1, SEL1L and p97, similar to the glycosylated SHH. While EDEM2 was required for ERAD of both glycosylated and non-glycosylated SHHs, EDEM3 was only necessary for glycosylated SHH and EDEM1 was dispensable for both. Degradation of SHH and N278A also required OS-9, but not the related lectin XTP3-B. Robust interaction of both EDEM2 and OS-9 with a non-glycosylated SHH variant indicates that the misfolded polypeptide backbone, rather than a glycan signature, functions as the predominant signal for recognition for ERAD. Notably, SHH-N278A is the first nonglycosylated substrate to require EDEM2 for recognition and targeting for ERAD. EDEM2 also interacts with calnexin and SEL1L, suggesting a potential avenue by which misfolded glycoproteins may be shunted towards SEL1L and ERAD rather than being released into the secretory pathway. Thus, ER lectins participate in the recognition and delivery of misfolded ER substrates differently in mammals, with an underlying mechanism distinct from that of S. cerevisiae.

  5. Previously unknown role for the ubiquitin ligase Ubr1 in endoplasmic reticulum-associated protein degradation.

    Science.gov (United States)

    Stolz, Alexandra; Besser, Stefanie; Hottmann, Heike; Wolf, Dieter H

    2013-09-17

    Quality control and degradation of misfolded proteins are essential processes of all cells. The endoplasmic reticulum (ER) is the entry site of proteins into the secretory pathway in which protein folding occurs and terminally misfolded proteins are recognized and retrotranslocated across the ER membrane into the cytosol. Here, proteins undergo polyubiquitination by one of the membrane-embedded ubiquitin ligases, in yeast Hrd1/Der3 (HMG-CoA reductase degradation/degradation of the ER) and Doa10 (degradation of alpha), and are degraded by the proteasome. In this study, we identify cytosolic Ubr1 (E3 ubiquitin ligase, N-recognin) as an additional ubiquitin ligase that can participate in ER-associated protein degradation (ERAD) in yeast. We show that two polytopic ERAD substrates, mutated transporter of the mating type a pheromone, Ste6* (sterile), and cystic fibrosis transmembrane conductance regulator, undergo Ubr1-dependent degradation in the presence and absence of the canonical ER ubiquitin ligases. Whereas in the case of Ste6* Ubr1 is specifically required under stress conditions such as heat or ethanol or in the absence of the canonical ER ligases, efficient degradation of human cystic fibrosis transmembrane conductance regulator requires function of Ubr1 already in wild-type cells under standard growth conditions. Together with the Hsp70 (heat shock protein) chaperone Ssa1 (stress-seventy subfamily A) and the AAA-type ATPase Cdc48 (cell division cycle), Ubr1 directs the substrate to proteasomal degradation. These data unravel another layer of complexity in ERAD.

  6. Biodegradability of HCH in agricultural soils from Guadeloupe (French West Indies): identification of the lin genes involved in the HCH degradation pathway.

    Science.gov (United States)

    Laquitaine, L; Durimel, A; de Alencastro, L F; Jean-Marius, C; Gros, O; Gaspard, S

    2016-01-01

    Banana has been a main agricultural product in the French West Indies (Guadeloupe and Martinique) since the 1960s. This crop requires the intensive use of pesticides to prevent attacks by insect pests. Chlorinated pesticides, such as hexachlorocyclohexane (HCH), chlordecone and dieldrin, were used until the beginning of the 1990s, resulting in a generalized diffuse contamination of the soil and water in the areas of banana production, hence the need to develop solutions for cleanup of the polluted sites. The aims of this work were (i) to assess lindane degradation in soil slurry microcosms treated with lindane at 10 mg/L and (ii) to detect the catabolic genes involved in the HCH degradation pathway. The soil slurry microcosm system showed a 40% lindane degradation efficiency at the end of a 30-day experiment. Lower lindane removal was also detected in the abiotic controls, probably caused by pesticide adsorption to soil particles. Indeed, the lindane concentration decreased from 6000 to 1330 ng/mL and from 800 to 340 ng/mL for the biotic and abiotic soils, respectively. Nevertheless, some of the genes involved in the HCH degradation pathway were amplified by polymerase chain reaction (PCR) from crude deoxyribonucleic acid (DNA) extracted from the Guadeloupe agricultural soil, suggesting that HCH degradation is probably mediated by bacteria closely related to the family Sphingomonadaceae.

  7. Genetic associations of type 2 diabetes with islet amyloid polypeptide processing and degrading pathways in asian populations.

    Directory of Open Access Journals (Sweden)

    Vincent Kwok Lim Lam

    Full Text Available Type 2 diabetes (T2D is a complex disease characterized by beta cell dysfunctions. Islet amyloid polypeptide (IAPP is highly conserved and co-secreted with insulin with over 40% of autopsy cases of T2D showing islet amyloid formation due to IAPP aggregation. Dysregulation in IAPP processing, stabilization and degradation can cause excessive oligomerization with beta cell toxicity. Previous studies examining genetic associations of pathways implicated in IAPP metabolism have yielded conflicting results due to small sample size, insufficient interrogation of gene structure and gene-gene interactions. In this multi-staged study, we screened 89 tag single nucleotide polymorphisms (SNPs in 6 candidate genes implicated in IAPP metabolism and tested for independent and joint associations with T2D and beta cell dysfunctions. Positive signals in the stage-1 were confirmed by de novo and in silico analysis in a multi-centre unrelated case-control cohort. We examined the association of significant SNPs with quantitative traits in a subset of controls and performed bioinformatics and relevant functional analyses. Amongst the tag SNPs, rs1583645 in carboxypeptidase E (CPE and rs6583813 in insulin degrading enzyme (IDE were associated with 1.09 to 1.28 fold increased risk of T2D (P Meta = 9.4×10(-3 and 0.02 respectively in a meta-analysis of East Asians. Using genetic risk scores (GRS with each risk variant scoring 1, subjects with GRS≥3 (8.2% of the cohort had 56% higher risk of T2D than those with GRS = 0 (P = 0.01. In a subcohort of control subjects, plasma IAPP increased and beta cell function index declined with GRS (P = 0.008 and 0.03 respectively. Bioinformatics and functional analyses of CPE rs1583645 predicted regulatory elements for chromatin modification and transcription factors, suggesting differential DNA-protein interactions and gene expression. Taken together, these results support the importance of dysregulation of IAPP

  8. Genetic Associations of Type 2 Diabetes with Islet Amyloid Polypeptide Processing and Degrading Pathways in Asian Populations

    Science.gov (United States)

    Lam, Vincent Kwok Lim; Ma, Ronald Ching Wan; Lee, Heung Man; Hu, Cheng; Park, Kyong Soo; Furuta, Hiroto; Wang, Ying; Tam, Claudia Ha Ting; Sim, Xueling; Ng, Daniel Peng-Keat; Liu, Jianjun; Wong, Tien-Yin; Tai, E. Shyong; Morris, Andrew P.; Tang, Nelson Leung Sang; Woo, Jean; Leung, Ping Chung; Kong, Alice Pik Shan; Ozaki, Risa; Jia, Wei Ping; Lee, Hong Kyu; Nanjo, Kishio; Xu, Gang; Ng, Maggie Chor Yin; So, Wing-Yee; Chan, Juliana Chung Ngor

    2013-01-01

    Type 2 diabetes (T2D) is a complex disease characterized by beta cell dysfunctions. Islet amyloid polypeptide (IAPP) is highly conserved and co-secreted with insulin with over 40% of autopsy cases of T2D showing islet amyloid formation due to IAPP aggregation. Dysregulation in IAPP processing, stabilization and degradation can cause excessive oligomerization with beta cell toxicity. Previous studies examining genetic associations of pathways implicated in IAPP metabolism have yielded conflicting results due to small sample size, insufficient interrogation of gene structure and gene-gene interactions. In this multi-staged study, we screened 89 tag single nucleotide polymorphisms (SNPs) in 6 candidate genes implicated in IAPP metabolism and tested for independent and joint associations with T2D and beta cell dysfunctions. Positive signals in the stage-1 were confirmed by de novo and in silico analysis in a multi-centre unrelated case-control cohort. We examined the association of significant SNPs with quantitative traits in a subset of controls and performed bioinformatics and relevant functional analyses. Amongst the tag SNPs, rs1583645 in carboxypeptidase E (CPE) and rs6583813 in insulin degrading enzyme (IDE) were associated with 1.09 to 1.28 fold increased risk of T2D (PMeta = 9.4×10−3 and 0.02 respectively) in a meta-analysis of East Asians. Using genetic risk scores (GRS) with each risk variant scoring 1, subjects with GRS≥3 (8.2% of the cohort) had 56% higher risk of T2D than those with GRS = 0 (P = 0.01). In a subcohort of control subjects, plasma IAPP increased and beta cell function index declined with GRS (P = 0.008 and 0.03 respectively). Bioinformatics and functional analyses of CPE rs1583645 predicted regulatory elements for chromatin modification and transcription factors, suggesting differential DNA-protein interactions and gene expression. Taken together, these results support the importance of dysregulation of IAPP metabolism in

  9. Small heat shock proteins target mutant cystic fibrosis transmembrane conductance regulator for degradation via a small ubiquitin-like modifier-dependent pathway.

    Science.gov (United States)

    Ahner, Annette; Gong, Xiaoyan; Schmidt, Bela Z; Peters, Kathryn W; Rabeh, Wael M; Thibodeau, Patrick H; Lukacs, Gergely L; Frizzell, Raymond A

    2013-01-01

    Small heat shock proteins (sHsps) bind destabilized proteins during cell stress and disease, but their physiological functions are less clear. We evaluated the impact of Hsp27, an sHsp expressed in airway epithelial cells, on the common protein misfolding mutant that is responsible for most cystic fibrosis. F508del cystic fibrosis transmembrane conductance regulator (CFTR), a well-studied protein that is subject to cytosolic quality control, selectively associated with Hsp27, whose overexpression preferentially targeted mutant CFTR to proteasomal degradation. Hsp27 interacted physically with Ubc9, the small ubiquitin-like modifier (SUMO) E2 conjugating enzyme, implying that F508del SUMOylation leads to its sHsp-mediated degradation. Enhancing or disabling the SUMO pathway increased or blocked Hsp27's ability to degrade mutant CFTR. Hsp27 promoted selective SUMOylation of F508del NBD1 in vitro and of full-length F508del CFTR in vivo, which preferred endogenous SUMO-2/3 paralogues that form poly-chains. The SUMO-targeted ubiquitin ligase (STUbL) RNF4 recognizes poly-SUMO chains to facilitate nuclear protein degradation. RNF4 overexpression elicited F508del degradation, whereas Hsp27 knockdown blocked RNF4's impact on mutant CFTR. Similarly, the ability of Hsp27 to degrade F508del CFTR was lost during overexpression of dominant-negative RNF4. These findings link sHsp-mediated F508del CFTR degradation to its SUMOylation and to STUbL-mediated targeting to the ubiquitin-proteasome system and thereby implicate this pathway in the disposal of an integral membrane protein.

  10. The Role of Lectin-Carbohydrate Interactions in the Regulation of ER-Associated Protein Degradation

    Directory of Open Access Journals (Sweden)

    Monika Słomińska-Wojewódzka

    2015-05-01

    Full Text Available Proteins entering the secretory pathway are translocated across the endoplasmic reticulum (ER membrane in an unfolded form. In the ER they are restricted to a quality control system that ensures correct folding or eventual degradation of improperly folded polypeptides. Mannose trimming of N-glycans on newly synthesized proteins plays an important role in the recognition and sorting of terminally misfolded glycoproteins for ER-associated protein degradation (ERAD. In this process misfolded proteins are retrotranslocated into the cytosol, polyubiquitinated, and eventually degraded by the proteasome. The mechanism by which misfolded glycoproteins are recognized and recruited to the degradation machinery has been extensively studied during last decade. In this review, we focus on ER degradation-enhancing α-mannosidase-like protein (EDEM family proteins that seem to play a key role in the discrimination between proteins undergoing a folding process and terminally misfolded proteins directed for degradation. We describe interactions of EDEM proteins with other components of the ERAD machinery, as well as with various protein substrates. Carbohydrate-dependent interactions together with N-glycan-independent interactions seem to regulate the complex process of protein recognition and direction for proteosomal degradation.

  11. Activation of the cAMP/PKA pathway induces UT-A1 urea transporter monoubiquitination and targets it for lysosomal degradation.

    Science.gov (United States)

    Su, Hua; Chen, Minguang; Sands, Jeff M; Chen, Guangping

    2013-12-15

    Regulation of urea transporter UT-A1 in the kidney is important for the urinary concentrating mechanism. We previously reported that activation of the cAMP/PKA pathway by forskolin (FSK) leads to UT-A1 ubiquitination, endocytosis, and degradation. In this study, we discovered that FSK-induced UT-A1 ubiquitination is monoubiquitination as judged by immunoblotting with specific ubiquitin antibodies to the different linkages of the ubiquitin chain. UT-A1 monoubiquitination induced by FSK was processed mainly on the cell plasma membrane. Monoubiquitination facilitates UT-A1 endocytosis, and internalized UT-A1 is accumulated in the early endosome. Inhibition of ubiquitination by E1 ubiquitin-activating enzyme inhibitor PYR-41 significantly reduced FSK-induced UT-A1 endocytosis and degradation. Interestingly, FSK-stimulated UT-A1 degradation occurs through a lysosomal protein degradation system. We further found that the PKA phosphorylation sites of UT-A1 at Ser486 and Ser499 are required for FSK-induced UT-A1 monoubiquitination. The physiological significance was confirmed using rat kidney inner medullary collecting duct suspensions, which showed that vasopressin treatment promotes UT-A1 ubiquitination. We conclude that unlike under basal conditions in which UT-A1 is subject to polyubiquitination and proteasome-mediated protein degradation, activation of UT-A1 by FSK induces UT-A1 monoubiquitination and protein lysosomal degradation.

  12. The ubiquitin+proteasome protein degradation pathway as a therapeutic strategy in the treatment of solid tumor malignancies.

    Science.gov (United States)

    Driscoll, James J; Minter, Alex; Driscoll, Daniel A; Burris, Jason K

    2011-02-01

    A concept that currently steers the development of cancer therapies has been that agents directed against specific proteins that facilitate tumorigenesis or maintain a malignant phenotype will have greater efficacy, less toxicity and a more sustained response relative to traditional cytotoxic chemotherapeutic agents. The clinical success of the targeted agent Imatinib mesylate as an inhibitor of the tyrosine kinase associated with the breakpoint cluster region-Abelson oncogene locus (BCR-ABL) in the treatment of Philadelphia-positive chronic myelogenous leukemia (CML) has served as a paradigm. While intellectually gratifying, the selective targeting of a single driver event by a small molecule, e.g., kinase inhibitor, to dampen a tumor-promoting pathway in the treatment of solid tumors is limited by many factors. Focus can alternatively be placed on targeting fundamental cellular processes that regulate multiple events, e.g., protein degradation, through the Ubiquitin (Ub)+Proteasome System (UPS). The UPS plays a critical role in modulating numerous cellular proteins to regulate cellular processes such as signal transduction, growth, proliferation, differentiation and apoptosis. Clinical success with the proteasome inhibitor bortezomib revolutionized treatment of B-cell lineage malignancies such as Multiple Myeloma (MM). However, many patients harbor primary resistance and do not respond to bortezomib and those that do respond inevitably develop resistance (secondary resistance). The lack of clinical efficacy of proteasome inhibitors in the treatment of solid tumors may be linked mechanistically to the resistance detected during treatment of hematologic malignancies. Potential mechanisms of resistance and means to improve the response to proteasome inhibitors in solid tumors are discussed.

  13. Photolysis of model emerging contaminants in ultra-pure water: kinetics, by-products formation and degradation pathways.

    Science.gov (United States)

    Benitez, F Javier; Acero, Juan L; Real, Francisco J; Roldan, Gloria; Rodriguez, Elena

    2013-02-01

    The photolysis of five frequent emerging contaminants (Benzotriazole, Chlorophene, N,N-diethyl-m-toluamide or DEET, Methylindole, and Nortriptyline HCl) was investigated in ultrapure water under monochromatic ultraviolet radiation at 254 nm and by a combination of UV and hydrogen peroxide. The results revealed that the photolysis rates followed first-order kinetics, with rate constant values depending on the nature of the specific compound, the pH, and the presence or absence of the scavenger tert-butanol. Quantum yields were also determined and values in the range of 53.8 × 10⁻³ - 9.4 × 10⁻³ mol E⁻¹ for Benzotriazole, 525 × 10⁻³ - 469 × 10⁻³ mol E⁻¹ for Chlorophene, 2.8 × 10⁻³ - 0.9 × 10⁻³ mol E⁻¹ for DEET, 108 × 10⁻³ - 165 × 10⁻³ mol E⁻¹ for Methylindole, and 13.8 × 10⁻³ - 15.0 × 10⁻³ mol E⁻¹ for Nortriptyline were obtained. The study also found that the UV/H₂O₂ process enhanced the oxidation rate in comparison to direct photolysis. High-performance liquid chromatography coupled to electrospray ionization quadrupole time-of-flight mass spectrometry (HPLC-ESI-QTOF-MS) technique was applied to the concentrations evaluation and further identification of the parent compounds and their by-products, which allowed the proposal of the degradation pathways for each compound. Finally, in order to assess the aquatic toxicity in the photodegradation of these compounds, the Vibrio fischeri acute toxicity test was used, and the results indicated an initial increase of this parameter in all cases, followed by a decrease in the specific case of Benzotriazole, DEET, Methylindole, and Chlorophene.

  14. GABA shunt and polyamine degradation pathway on γ-aminobutyric acid accumulation in germinating fava bean (Vicia faba L.) under hypoxia.

    Science.gov (United States)

    Yang, Runqiang; Guo, Qianghui; Gu, Zhenxin

    2013-01-01

    GABA shunt and polyamine degradation pathway on γ-aminobutyric acid (GABA) accumulation in germinating fava bean under hypoxia was investigated. GABA content, GAD and DAO activity were significantly increased under hypoxia treatment. Glu and polyamine contents enhanced largely and thus supplied as sufficient substrates for GABA formation. In contrast, GABA content decreased, mainly in the embryo, after removing the hypoxia stress. DAO activity, Glu and polyamines contents decreased, while an increment of GAD activity was observed. This indicated that GAD activity can be not only regulated by hypoxia, but by the rapid growth of embryo after the recovery from hypoxia stress. When treated with AG, DAO activity was almost inhibited completely, and the GABA content decreased by 32.96% and 32.07% after treated for 3 and 5 days, respectively. Hence, it can be inferred that about 30% of GABA formed in germinating fava bean under hypoxia was supplied by polyamine degradation pathway.

  15. Eradication of Helicobacter pylori infection.

    Science.gov (United States)

    Wu, Tzung-Shiun; Hu, Huang-Ming; Kuo, Fu-Chen; Kuo, Chao-Hung

    2014-04-01

    Eradication of Helicobacter pylori infection has become an important issue recently, because this bacterial species cluster can cause many gastrointestinal diseases. Elevated antibiotic resistance is related to an increasing failure rate of H. pylori eradication. Standard triple therapy is still the first-line therapy; however, according to the Maastricht IV Consensus Report, it should be abandoned in areas of high clarithromycin resistance. Alternative first-line therapies include bismuth-containing quadruple therapy, sequential, concomitant, and hybrid therapies. Quinolone-based triple therapy may be considered as first-line therapy in areas of clarithromycin resistance >15-20% and quinolone resistance <10%. Unique second-line therapy is still unclear, and bismuth-containing quadruple therapy or levofloxacin-based triple therapy can be used as rescue treatment. Third-line therapy should be under culture guidance to select the most effective regimens (such as levofloxacin-based, rifabutin-based, or furazolidone-based therapies). Antibiotics resistance, patient compliance, and CYP 2C19 genotypes could influence the outcome. Clinicians should use antibiotics according to local reports.

  16. CDC48 function during TMV infection: regulation of virus movement and replication by degradation?

    Science.gov (United States)

    Niehl, Annette; Amari, Khalid; Heinlein, Manfred

    2013-02-01

    Cell-division-cycle protein 48 (CDC48) is an essential, conserved ATP-driven chaperone in eukaryotic cells, which functions in diverse cellular processes including the targeting of misfolded and aggregated proteins for degradation via proteasomal and aggresomal-autophagic pathways. We recently demonstrated that plant CDC48 localizes to and interacts with Tobacco mosaic virus (TMV) movement protein (MP) in ER-associated viral protein inclusions. Our data suggest that CDC48 participates in the clearance of these viral protein inclusions in an ER-assisted protein degradation (ERAD)-like mechanism. As TMV MP-inclusions formed at late infection stages resemble aggresomes, we here propose that TMV MP enters both, ERAD-like and aggresomal pathways in its host cells and that CDC48 coordinates these processes. Moreover, as viruses often exploit host pathways for replication and spread, we propose a model in which CDC48 functions in the degradation pathway of overaccumulating viral protein and also actively participates in the regulation of TMV replication and cell-to-cell movement. 

  17. Cloning and expression of meta-cleavage enzyme (CarB of carbazole degradation pathway from Pseudomonas stutzeri

    Directory of Open Access Journals (Sweden)

    Ariane Leites Larentis

    2005-06-01

    Full Text Available In this work, the 1082bp PCR product corresponding to carBaBb genes that encode the heterotetrameric enzyme 2'-aminobiphenyl-2,3-diol 1,2-dioxygenase (CarB, involved in the Pseudomonas stutzeri ATCC 31258 carbazole degradation pathway, was cloned using the site-specific recombination system. Recombinant clones were confirmed by PCR, restriction enzyme digestion and sequencing. CarB dioxygenase was expressed in high levels and in active form in Escherichia coli BL21-SI using the His-tagged expression vector pDEST TM17 and salt induction for 4h.Carbazol e seus derivados são compostos nitrogenados aromáticos, presentes comumente em petróleo e potencialmente poluentes. A rota de biodegradação de carbazol a ácido antranílico em Pseudomonas sp. é composta por três enzimas responsáveis, respectivamente, pelas reações de dioxigenação angular, meta-clivagem e hidrólise. A segunda enzima da rota, 2'-aminobifenil-2,3-diol 1,2-dioxigenase (CarB, codificada por dois genes (carBa e carBb, é um heterotetrâmero com atividade catalítica na quebra do anel catecol do susbtrato na posição meta. Neste trabalho, foi clonado o produto de PCR de 1082pb correspondente aos genes carBaBb da bactéria degradadora de carbazol Pseudomonas stutzeri ATCC 31258. A estratégia de clonagem empregada foi a de recombinação sítio-específica e a construção dos plasmídeos foi confirmada por PCR, digestão com enzima de restrição e seqüenciamento. A enzima ativa foi expressa em altas concentrações em vetor pDEST TM17 com cauda de histidina e promotor T7 em Escherichia coli BL21-SI com indução por NaCl durante 4h.

  18. Eradicating cancer cells: struggle with a chameleon

    NARCIS (Netherlands)

    Di, J.; Duiveman-de Boer, T.; Figdor, C.G.; Torensma, R.

    2011-01-01

    Eradication of cancer stem cells to abrogate tumor growth is a new treatment modality. However, like normal cells cancer cells show plasticity. Differentiated tumor stem cells can acquire stem cell properties when they gain access to the stem cell niche. This indicates that eradicating of stem cells

  19. Eradicating a Disease: Lessons from Mathematical Epidemiology

    Science.gov (United States)

    Glomski, Matthew; Ohanian, Edward

    2012-01-01

    Smallpox remains the only human disease ever eradicated. In this paper, we consider the mathematics behind control strategies used in the effort to eradicate smallpox, from the life tables of Daniel Bernoulli, to the more modern susceptible-infected-removed (SIR)-type compartmental models. In addition, we examine the mathematical feasibility of…

  20. H pylori recurrence after successful eradication

    Institute of Scientific and Technical Information of China (English)

    Yaron Niv

    2008-01-01

    Recurrence of H pylori after eradication is rare in developed countries and more frequent in developing countries.Recrudescence(recolonization of the same strain within 12 mo after eradication)rather than reinfection(colonization with a new strain,more than 12 mo after eradication)is considered to be responsiblefor most of the cases.This observation was confirmed only in developed countries,while in developing countries a recent meta-analysis demonstrated a high rate of reinfection.The proportion of H pylori annual recurrence was 2.67% and 13.00% in developed and developing countries,respectively.Nested meta-analysis(only cases with a longer follow-up and a negative 13CUBT a year after eradication)revealed annual recurrence rate of 1.45%[relative risk(RR),0.54]and 12.00%(RR,0.92)in developed and developing countries,respectively.These findings support the notion that in developed countries many cases of recurrence are due to recrudescence within the first year after eradication,with a 46% drop in the recurrence rate after the first year post eradication,while in developing countries reinfection is more pronounced,and continue at the same rate since eradication.A different approach for follow-up after H pylori eradication is probably needed in patients of developing countries,since reinfection is highly prevalent.

  1. Activated ClpP kills persisters and eradicates a chronic biofilm infection.

    Energy Technology Data Exchange (ETDEWEB)

    Conlon, Brian P.; Nakayasu, Ernesto S.; Fleck, Laura E.; LaFleur, Michael D.; Isabella, Vincent M.; Coleman, K.; Leonard, Steve N.; Smith, Richard D.; Adkins, Joshua N.; Lewis, Kim

    2013-11-21

    The current antibiotic crisis stems from two distinct phenomena-drug resistance, and drug tolerance. Resistance mechanisms such as drug efflux or modification prevent antibiotics from binding to their targets 1, allowing pathogens to grow. Antibiotic tolerance is the property of persister cells, phenotypic variants of regular bacteria 2. Antibiotics kill by corrupting targets, but these are inactive in dormant persisters, leading to tolerance. Persisters were first identified by Joseph Bigger in 1944, when he discovered a surviving sub-population of Staphylococcus following treatment with penicillin3. Persisters are largely responsible for recalcitrance of chronic diseases such as tuberculosis, and various infections associated with biofilms - endocarditis, osteomyelitis, infections of catheters and indwelling devices, and deep-seated infections of soft tissues 4. There are a number of redundant pathways involved in persister formation5,6 precluding development of drugs inhibiting their formation. The acyldepsipeptide antibiotic (ADEP 4) has been shown to activate the ClpP protease resulting in death of growing cells 7. Here we show that ADEP4 activated ClpP becomes a fairly non-specific protease and kills persister cells by degradation of over 400 intracellular targets. clpP mutants are resistant to ADEP4 7, but we find that they display increased susceptibility to killing by a range of conventional antibiotics. Combining ADEP4 with rifampicin leads to eradication of persisters, stationary and biofilm populations of Staphylococcus aureus in vitro and in a deep-seated murine infection. Target corruption/activation provides an approach to killing persisters and eradicating chronic infections.

  2. α-Amino acid containing degradable polymers as functional biomaterials: rational design, synthetic pathway, and biomedical applications.

    Science.gov (United States)

    Sun, Huanli; Meng, Fenghua; Dias, Aylvin A; Hendriks, Marc; Feijen, Jan; Zhong, Zhiyuan

    2011-06-13

    Currently, biomedical engineering is rapidly expanding, especially in the areas of drug delivery, gene transfer, tissue engineering, and regenerative medicine. A prerequisite for further development is the design and synthesis of novel multifunctional biomaterials that are biocompatible and biologically active, are biodegradable with a controlled degradation rate, and have tunable mechanical properties. In the past decades, different types of α-amino acid-containing degradable polymers have been actively developed with the aim to obtain biomimicking functional biomaterials. The use of α-amino acids as building units for degradable polymers may offer several advantages: (i) imparting chemical functionality, such as hydroxyl, amine, carboxyl, and thiol groups, which not only results in improved hydrophilicity and possible interactions with proteins and genes, but also facilitates further modification with bioactive molecules (e.g., drugs or biological cues); (ii) possibly improving materials biological properties, including cell-materials interactions (e.g., cell adhesion, migration) and degradability; (iii) enhancing thermal and mechanical properties; and (iv) providing metabolizable building units/blocks. In this paper, recent developments in the field of α-amino acid-containing degradable polymers are reviewed. First, synthetic approaches to prepare α-amino acid-containing degradable polymers will be discussed. Subsequently, the biomedical applications of these polymers in areas such as drug delivery, gene delivery and tissue engineering will be reviewed. Finally, the future perspectives of α-amino acid-containing degradable polymers will be evaluated.

  3. Degradation of ciprofloxacin by 280 nm ultraviolet-activated persulfate: Degradation pathway and intermediate impact on proteome of Escherichia coli.

    Science.gov (United States)

    Ye, Jin-Shao; Liu, Juan; Ou, Hua-Se; Wang, Lin-Lin

    2016-12-01

    In this study, the degradation of ciprofloxacin (CIP) was explored using ultraviolet activated persulfate (UV/PS) with 280 nm ultraviolet light-emitting diodes (UV-LEDs), and the toxicological assessment of degrading intermediates was performed using iTRAQ labeling quantitative proteomic technology. The quantitative mass spectrum results showed that 280 nm UV/PS treatment had a high transformation efficiency of CIP ([CIP] = 3 μM, [S2O8(2-)] = 210 μM, apparent rate constants 0.2413 min(-1)). The high resolution mass spectrum analyses demonstrated that the primary intermediates included C15H16FN3O3 (m/z 306.1248) and C17H18FN3O4 (m/z 348.1354). The former one was formed by the cleavage of piperazine ring, while the later one was generated by the addition of a hydroxyl on the quinolone backbone. The toxicological assessment demonstrated that 56 and 110 proteins had significant up regulations and down regulations, respectively, in the Escherichia coli exposed to degraded CIP compared to untreated CIP. The majority of up-regulated proteins, such as GapA, SodC, were associated with primary metabolic process rather than responses to stress and toxic substance, inferring that the moderate UV/PS treatment can reduce the antibacterial activity of CIP by incomplete mineralization. Consequently, these results provided a novel insight into the application of UV-LED/PS treatment as a promising removal methodology for quinolones. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Fucoidan inhibition of lung cancer in vivo and in vitro : role of the Smurf2-dependent ubiquitin proteasome pathway in TGFβ receptor degradation.

    Science.gov (United States)

    Hsu, Hsien-Yeh; Lin, Tung-Yi; Wu, Yu-Chung; Tsao, Shu-Ming; Hwang, Pai-An; Shih, Yu-Wei; Hsu, Jason

    2014-09-15

    Fucoidan, a polysaccharide extracted from brown seaweeds, reduces tumor cell proliferation. In this study, we demonstrate that fucoidan reduces tumor size in LLC1-xenograft male C57BL/6 mice. Moreover, we found that LLC1-bearing mice continuously fed fucoidan showed greater antitumor activity than mice with discontinuous feeding. Fucoidan inhibited the in vitro growth of lung cancer cells. Transforming growth factor β (TGFβ) receptors (TGFRs) play important roles in the regulation of proliferation and progression, and high TGFRI expression in lung cancer specimens is associated with a worse prognosis. Herein, using lung cancer cells, we found that fucoidan effectively reduces TGFRI and TGFRII protein levels in vivo and in vitro. Moreover, fucoidan reduces TGFR downstream signaling events, including those in Smad2/3 and non-Smad pathways: Akt, Erk1/2, and FAK phosphorylation. Furthermore, fucoidan suppresses lung cancer cell mobility upon TGFβ stimulation. To elucidate how fucoidan decreases TGFR proteins in lung cancer cells, we found that fucoidan enhances the ubiquitination proteasome pathway (UPP)-mediated degradation of TGFRs in A549 and CL1-5 cells. Mechanistically, fucoidan promotes Smurf2 and Smad7 to conjugate TGFRs, resulting in TGF degradation; however, Smurf2-shRNA abolishes fucoidan-enhanced UPP-mediated TGFR degradation. Our study is the first to identify a novel mechanism for the antitumor activity of fucoidan, namely decreasing tumor growth by modulating the TGFR/Smad7/Smurf2-dependent axis, leading to TGFR protein degradation and inhibition of lung cancer cell progression in vitro and in vivo. Our current findings indicate that fucoidan is a potential therapeutic agent or dietary supplementation for lung cancer, acting via the Smurf2-dependent ubiquitin degradation of TGFβ receptors.

  5. Reaction pathways of dimethyl phthalate degradation in TiO2-UV-O2 and TiO2-UV-Fe(VI) systems.

    Science.gov (United States)

    Yuan, Bao-ling; Li, Xiang-zhong; Graham, Nigel

    2008-05-01

    The photocatalytic degradation of dimethyl phthalate (DMP) in aqueous TiO2 suspension under UV illumination has been investigated using oxygen (O2) and ferrate (Fe(VI)) as electron acceptors. The experiments demonstrated that Fe(VI) was a more effective electron acceptor than O2 for scavenging the conduction band electrons from the surface of the catalyst. Some major intermediate products from DMP degradation were identified by HPLC and GC/MS analyses. The analytical results identified dimethyl 3-hydroxyphthalate and dimethyl 2-hydroxyphthalate as the two main intermediate products from the DMP degradation in the TiO2-UV-O2 system, while in contrast phthalic acid was found to be the main intermediate product in the TiO2-UV-Fe(VI) system. These findings indicate that DMP degradation in the TiO2-UV-O2 and TiO2-UV-Fe(VI) systems followed different reaction pathways. An electron spin resonance analysis confirmed that hydroxyl radicals existed in the TiO2-UV-O2 reaction system and an unknown radical species (most likely an iron-oxo species) is suspected to exist in the TiO2-UV-Fe(VI) reaction system. Two pathway schemes of DMP degradation in the TiO2-UV-O2 and TiO2-UV-Fe(VI) reaction systems are proposed. It is believed that the radicals formed in the TiO2-UV-O2 reaction system preferably attack the aromatic ring of the DMP, while in contrast the radicals formed in the TiO2-UV-Fe(VI) reaction systems attack the alkyl chain of DMP.

  6. Phosphate Shifted Oxygen Reduction Pathway on Fe@Fe2O3 Core-Shell Nanowires for Enhanced Reactive Oxygen Species Generation and Aerobic 4-Chlorophenol Degradation.

    Science.gov (United States)

    Mu, Yi; Ai, Zhihui; Zhang, Lizhi

    2017-07-18

    Phosphate ions widely exist in the environment. Previous studies revealed that the adsorption of phosphate ions on nanoscale zerovalent iron would generate a passivating oxide shell to block reactive sites and thus decrease the direct pollutant reduction reactivity of zerovalent iron. Given that molecular oxygen activation process is different from direct pollutant reduction with nanoscale zerovalent iron, it is still unclear how phosphate ions will affect molecular oxygen activation and reactive oxygen species generation with nanoscale zerovalent iron. In this study, we systematically studied the effect of phosphate ions on molecular oxygen activation with Fe@Fe2O3 nanowires, a special nanoscale zerovalent iron, taking advantages of rotating ring disk electrochemical analysis. It was interesting to find that the oxygen reduction pathway on Fe@Fe2O3 nanowires was gradually shifted from a four-electron reduction pathway to a sequential one-electron reduction one, along with increasing the phosphate ions concentration from 0 to 10 mmol·L(-1). This oxygen reduction pathway change greatly enhanced the molecular oxygen activation and reactive oxygen species generation performances of Fe@Fe2O3 nanowires, and thus increased their aerobic 4-chlorophenol degradation rate by 10 times. These findings shed insight into the possible roles of widely existed phosphate ions in molecular oxygen activation and organic pollutants degradation with nanoscale zerovalent iron.

  7. Non-degradative ubiquitination of the Notch1 receptor by the E3 ligase MDM2 activates the Notch signalling pathway.

    Science.gov (United States)

    Pettersson, Susanne; Sczaniecka, Matylda; McLaren, Lorna; Russell, Fiona; Gladstone, Karen; Hupp, Ted; Wallace, Maura

    2013-03-15

    The Notch receptor is necessary for modulating cell fate decisions throughout development, and aberrant activation of Notch signalling has been associated with many diseases, including tumorigenesis. The E3 ligase MDM2 (murine double minute 2) plays a role in regulating the Notch signalling pathway through its interaction with NUMB. In the present study we report that MDM2 can also exert its oncogenic effects on the Notch signalling pathway by directly interacting with the Notch 1 receptor through dual-site binding. This involves both the N-terminal and acidic domains of MDM2 and the RAM [RBP-Jκ (recombination signal-binding protein 1 for Jκ)-associated molecule] and ANK (ankyrin) domains of Notch 1. Although the interaction between Notch1 and MDM2 results in ubiquitination of Notch1, this does not result in degradation of Notch1, but instead leads to activation of the intracellular domain of Notch1. Furthermore, MDM2 can synergize with Notch1 to inhibit apoptosis and promote proliferation. This highlights yet another target for MDM2-mediated ubiquitination that results in activation of the protein rather than degradation and makes MDM2 an attractive target for drug discovery for both the p53 and Notch signalling pathways.

  8. Matrix Metalloproteinase-9 Leads to Claudin-5 Degradation via the NF-κB Pathway in BALB/c Mice with Eosinophilic Meningoencephalitis Caused by Angiostrongylus cantonensis

    Science.gov (United States)

    Chiu, Ping-Sung; Lai, Shih-Chan

    2013-01-01

    The epithelial barrier regulates the movement of ions, macromolecules, immune cells and pathogens. The objective of this study was to investigate the role of the matrix metalloproteinase (MMP)-9 in the degradation of tight junction protein during infection with rat nematode lungworm Angiostrongylus cantonensis. The results showed that phosphorylation of IκB and NF-κB was increased in mice with eosinophilic meningoencephalitis. Treatment with MG132 reduced the phosphorylation of NF-κB and the activity of MMP-9, indicating upregulation of MMP-9 through the NF-κB signaling pathway. Claudin-5 was reduced in the brain but elevated in the cerebrospinal fluid (CSF), implying that A. cantonensis infection caused tight junction breakdown and led to claudin-5 release into the CSF. Degradation of claudin-5 coincided with alteration of the blood-CSF barrier permeability and treatment with the MMP inhibitor GM6001 attenuated the degradation of claudin-5. These results suggested that degradation of claudin-5 was caused by MMP-9 in angiostrongyliasis meningoencephalitis. Claudin-5 could be used for the pathophysiologic evaluation of the blood-CSF barrier breakdown and tight junction disruption after infection with A. cantonensis. PMID:23505411

  9. Common Degradative Pathways of Morpholine, Thiomorpholine, and Piperidine by Mycobacterium aurum MO1: Evidence from 1H-Nuclear Magnetic Resonance and Ionspray Mass Spectrometry Performed Directly on the Incubation Medium

    Science.gov (United States)

    Combourieu, Bruno; Besse, Pascale; Sancelme, Martine; Godin, Jean-Philippe; Monteil, André; Veschambre, Henri; Delort, Anne-Marie

    2000-01-01

    In order to see if the biodegradative pathways for morpholine and thiomorpholine during degradation by Mycobacterium aurum MO1 could be generalized to other heterocyclic compounds, the degradation of piperidine by this strain was investigated by performing 1H-nuclear magnetic resonance directly with the incubation medium. Ionspray mass spectrometry, performed without purification of the samples, was also used to confirm the structure of some metabolites during morpholine and thiomorpholine degradation. The results obtained with these two techniques suggested a general pathway for degradation of nitrogen heterocyclic compounds by M. aurum MO1. The first step of the degradative pathway is cleavage of the C—N bond; this leads formation of an intermediary amino acid, which is followed by deamination and oxidation of this amino acid into a diacid. Except in the case of thiodiglycolate obtained from thiomorpholine degradation, the dicarboxylates are completely mineralized by the bacterial cells. A comparison with previously published data showed that this pathway could be a general pathway for degradation by other strains of members of the genus Mycobacterium. PMID:10919768

  10. The Challenge of Global Poliomyelitis Eradication.

    Science.gov (United States)

    Garon, Julie R; Cochi, Stephen L; Orenstein, Walter A

    2015-12-01

    In the United States during the 1950's, polio was on the forefront of every provider and caregiver's mind. Today, most providers in the United States have never seen a case. The Global Polio Eradication Initiative (GPEI), which began in 1988 has reduced the number of cases by over 99%. The world is closer to achieving global eradication of polio than ever before but as long as poliovirus circulates anywhere in the world, every country is vulnerable. The global community can support the polio eradication effort through continued vaccination, surveillance, enforcing travel regulations and contributing financial support, partnerships and advocacy.

  11. MIR125B1 represses the degradation of the PML-RARA oncoprotein by an autophagy-lysosomal pathway in acute promyelocytic leukemia.

    Science.gov (United States)

    Zeng, Cheng-Wu; Chen, Zhen-Hua; Zhang, Xing-Ju; Han, Bo-Wei; Lin, Kang-Yu; Li, Xiao-Juan; Wei, Pan-Pan; Zhang, Hua; Li, Yangqiu; Chen, Yue-Qin

    2014-10-01

    Acute promyelocytic leukemia (APL) is characterized by the t(15;17)-associated PML-RARA fusion gene. We have previously found that MIR125B1 is highly expressed in patients with APL and may be associated with disease pathogenesis; however, the mechanism by which MIR125B1 exerts its oncogenic potential has not been fully elucidated. Here, we demonstrated that MIR125B1 abundance correlates with the PML-RARA status. MIR125B1 overexpression enhanced PML-RARA expression and inhibited the ATRA-induced degradation of the PML-RARA oncoprotein. RNA-seq analysis revealed a direct link between the PML-RARA degradation pathway and MIR125B1-arrested differentiation. We further demonstrated that the MIR125B1-mediated blockade of PML-RARA proteolysis was regulated via an autophagy-lysosomal pathway, contributing to the inhibition of APL differentiation. Furthermore, we identified DRAM2 (DNA-damage regulated autophagy modulator 2), a critical regulator of autophagy, as a novel target that was at least partly responsible for the function of MIR125B1 involved in autophagy. Importantly, the knockdown phenotypes for DRAM2 are similar to the effects of overexpressing MIR125B1 as impairment of PML-RARA degradation, inhibition of autophagy, and myeloid cell differentiation arrest. These effects of MIR125B1 and its target DRAM2 were further confirmed in an APL mouse model. Thus, MIR125B1 dysregulation may interfere with the effectiveness of ATRA-mediated differentiation through an autophagy-dependent pathway, representing a novel potential APL therapeutic target.

  12. Poverty eradication: a new paradigm.

    Science.gov (United States)

    Pethe, V P

    1998-08-01

    This article offers a new paradigm for eradicating poverty in India. It was assumed incorrectly by Mahatma Gandhi that a good society without mass poverty would follow after independence. India copied Western models of development and developed giant factories, big dams, and megacities. Agriculture did not expand the number of jobs for people. The Western paradigm failed in India because of the false assumption of "trickle down" of income to the masses. The targeted programs to the poor did not directly benefit enough of the poor. Mega-industrialization led to reduced employment and higher skill needs. The model failed mainly because it was a proxy and relied on indirect ways of reaching the poor. The models failed to be adapted to conditions in India. The Swadeshi paradigm is a direct model for addressing mass poverty. Poverty is affected by immediate, intermediate, and ultimate determinants. Poverty begets social and economic problems, such as ignorance, ill health, high fertility, unemployment, and crime. In India and developing countries, mass poverty results from under use of human resources; lack of equal opportunities; and an outdated non-egalitarian social structure, an unjust global economic order, human cruelty, and erosion of ethical values. Indians are squandering their precious resources mimicking Western consumerism. Poverty leads to rapid population growth. People become productive assets with universal literacy, compulsory and free education, health services and sanitation, vocational training, and work ethics. India needs people-oriented policies with less emphasis on capital accumulation.

  13. NEDD4 E3 ligase inhibits the activity of the Hippo pathway by targeting LATS1 for degradation.

    Science.gov (United States)

    Salah, Zaidoun; Cohen, Sherri; Itzhaki, Ella; Aqeilan, Rami I

    2013-12-15

    Proper regulation of cell proliferation, cell apoptosis, and cell death are vital for the development and survival of living organisms. Failure or dysfunction of any of these processes can have devastating effects, including cancer. The Hippo pathway, first discovered in Drosophila, has been found to be a major growth-regulatory signaling pathway that controls these crucial processes and has been implicated in cell-progress regulation and organ size determination. Abnormal regulation of this pathway has been found in several cancer types. However, the mechanisms that regulate the pathway and its core members yet have to be elucidated. One of the main core components of this pathway is LATS1, a serine/threonine kinase. Therefore, understanding how LATS1 activity is regulated is expected to shed light on new mechanisms that regulate the Hippo pathway. In the current work, we identified several potential LATS1 regulators and proved that NEDD4 E3 ubiquitin ligase controls LATS1 stability. We demonstrate that NEDD4 directly interacts with LATS1, leading to ubiquitination and decreased levels of LATS1 and, thus, increased YAP localization in the nucleus, which subsequently increases the transcriptional activity of YAP. As such, we show that NEDD4 acts as an additional regulator of the Hippo pathway on the protein level via interactions between WW domain-containing and PPxY motif-containing proteins. These findings might be applied in the development of new therapeutic approaches through the activation of LATS1.

  14. Arctigenin promotes degradation of inducible nitric oxide synthase through CHIP-associated proteasome pathway and suppresses its enzyme activity.

    Science.gov (United States)

    Yao, Xiangyang; Li, Guilan; Lü, Chaotian; Xu, Hui; Yin, Zhimin

    2012-10-01

    Arctigenin, a natural dibenzylbutyrolactone lignan compound, has been reported to possess anti-inflammatory properties. Previous works showed that arctigenin decreased lipopolysaccharide (LPS)-induced iNOS at transcription level. However, whether arctigenin could regulate iNOS at the post-translational level is still unclear. In the present study, we demonstrated that arctigenin promoted the degradation of iNOS which is expressed under LPS stimulation in murine macrophage-like RAW 264.7 cells. Such degradation of iNOS protein is due to CHIP-associated ubiquitination and proteasome-dependency. Furthermore, arctigenin decreased iNOS phosphorylation through inhibiting ERK and Src activation, subsequently suppressed iNOS enzyme activity. In conclusion, our research displays a new finding that arctigenin can promote the ubiqitination and degradation of iNOS after LPS stimulation. iNOS activity regulated by arctigenin is likely to involve a multitude of crosstalking mechanisms.

  15. Synthesized TiO{sub 2}/ZSM-5 composites used for the photocatalytic degradation of azo dye: Intermediates, reaction pathway, mechanism and bio-toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Kefu; Hu, Xin-Yan [College of the Environment and Ecology, Xiamen University, Xiamen (China); Chen, Bor-Yann; Hsueh, Chung-Chuan [Department of Chemical and Materials Engineering, National I-Lan University, I-Lan, Taiwan (China); Zhang, Qian [Department of Environmental Engineering, National Taiwan University, Taipei, Taiwan (China); Wang, Jiajie; Lin, Yu-Jung [College of the Environment and Ecology, Xiamen University, Xiamen (China); Chang, Chang-Tang, E-mail: ctchang73222@gmail.com [Department of Environmental Engineering, National I-Lan University, I-Lan, Taiwan (China)

    2016-10-15

    Highlights: • The major photo-catalytic degradation pathway of azo-dye was elaborated according to the identification of by-products from GC–MS and IC analysis. • Comparative assessment on characteristics of abiotic and biotic dye decolorization was analyzed. • EDTA (hole scavengers) and t-BuOH (radical scavengers) were used to determine the main active oxidative species in the system. • The toxicity effects of degradation intermediates of Reactive Black 5 (RB5) on the cellular respiratory activity were assessed. - Abstract: In this study, a one-step solid dispersion method was used to synthesize titanium dioxide (TiO{sub 2})/Zeolite Socony Mobil-5 (ZSM-5) composites with substantially reduced time and energy consumption. A degradation efficiency of more than 95% was achieved within 10 min using 50% PTZ (synthesized TiO{sub 2}/ZSM-5 composites with TiO{sub 2} contents of 50 wt% loaded on ZSM-5) at pH 7 and 25 °C. The possible degradation pathway of azo-dye Reactive Black 5 (RB5) was investigated using gas chromatography–mass spectrometry and ion chromatography (IC). The bonds between the N atoms and naphthalene groups are likely attacked first and cleaved by hydroxyl radicals, ultimately resulting in the decolorization and mineralization of the azo dye. A comparative assessment of the characteristics of abiotic and biotic dye decolorization was completed. In addition, the toxicity effects of the degradation intermediates of azo-dye RB5 on cellular respiratory activity were analyzed. The bio-toxicity results showed that the decay rate constants of CO{sub 2} production from the azo-dye RB5 samples at different degradation times increased initially and subsequently decreased, indicating that intermediates of higher toxicity could adhere to the catalyst surface and gradually destroyed by further photocatalytic oxidation. Additionally, EDTA (hole scavengers) and t-BuOH (radical scavengers) were used to detect the main active oxidative species in the system

  16. Oxidative degradation of decabromodiphenyl ether (BDE 209) by potassium permanganate: reaction pathways, kinetics, and mechanisms assisted by density functional theory calculations.

    Science.gov (United States)

    Shi, Jiaqi; Qu, Ruijuan; Feng, Mingbao; Wang, Xinghao; Wang, Liansheng; Yang, Shaogui; Wang, Zunyao

    2015-04-07

    This study found that decabromodiphenyl ether (BDE 209) could be oxidized effectively by potassium permanganate (KMnO4) in sulfuric acid medium. A total of 15 intermediate oxidative products were detected. The reaction pathways were proposed, which primarily included cleavage of the ether bond to form pentabromophenol. Direct oxidation on the benzene ring also played an important role because hydroxylated polybrominated diphenyl ethers (PBDEs) were produced during the oxidation process. The degradation occurred dramatically in the first few minutes and fitted pseudo-first-order kinetics. Increasing the water content decelerated the reaction rate, whereas increasing the temperature facilitated the reaction. In addition, density functional theory (DFT) was employed to determine the frontier molecular orbital (FMO) and frontier electron density (FED) of BDE 209 and the oxidative products. The theoretical calculation results confirmed the proposed reaction pathways.

  17. Identification and characterization of the furfural and 5-(hydroxymethyl)furfural degradation pathways of Cupriavidus basilensis HMF14

    OpenAIRE

    Koopman, Frank; Wierckx, Nick; de Winde, Johannes H; Ruijssenaars, Harald J.

    2010-01-01

    The toxic fermentation inhibitors in lignocellulosic hydrolysates pose significant problems for the production of second-generation biofuels and biochemicals. Among these inhibitors, 5-(hydroxymethyl)furfural (HMF) and furfural are specifically notorious. In this study, we describe the complete molecular identification and characterization of the pathway by which Cupriavidus basilensis HMF14 metabolizes HMF and furfural. The identification of this pathway enabled the construction of an HMF an...

  18. Metabolic analysis of the soil microbe Dechloromonas aromatica str. RCB: indications of a surprisingly complex life-style and cryptic anaerobic pathways for aromatic degradation

    Directory of Open Access Journals (Sweden)

    Feil Helene

    2009-08-01

    Full Text Available Abstract Background Initial interest in Dechloromonas aromatica strain RCB arose from its ability to anaerobically degrade benzene. It is also able to reduce perchlorate and oxidize chlorobenzoate, toluene, and xylene, creating interest in using this organism for bioremediation. Little physiological data has been published for this microbe. It is considered to be a free-living organism. Results The a priori prediction that the D. aromatica genome would contain previously characterized "central" enzymes to support anaerobic aromatic degradation of benzene proved to be false, suggesting the presence of novel anaerobic aromatic degradation pathways in this species. These missing pathways include the benzylsuccinate synthase (bssABC genes (responsible for fumarate addition to toluene and the central benzoyl-CoA pathway for monoaromatics. In depth analyses using existing TIGRfam, COG, and InterPro models, and the creation of de novo HMM models, indicate a highly complex lifestyle with a large number of environmental sensors and signaling pathways, including a relatively large number of GGDEF domain signal receptors and multiple quorum sensors. A number of proteins indicate interactions with an as yet unknown host, as indicated by the presence of predicted cell host remodeling enzymes, effector enzymes, hemolysin-like proteins, adhesins, NO reductase, and both type III and type VI secretory complexes. Evidence of biofilm formation including a proposed exopolysaccharide complex and exosortase (epsH are also present. Annotation described in this paper also reveals evidence for several metabolic pathways that have yet to be observed experimentally, including a sulphur oxidation (soxFCDYZAXB gene cluster, Calvin cycle enzymes, and proteins involved in nitrogen fixation in other species (including RubisCo, ribulose-phosphate 3-epimerase, and nif gene families, respectively. Conclusion Analysis of the D. aromatica genome indicates there is much to be

  19. Metabolic analysis of the soil microbe Dechloromonas aromatica str. RCB: indications of a surprisingly complex life-style and cryptic anaerobic pathways for aromatic degradation

    Energy Technology Data Exchange (ETDEWEB)

    Salinero, Kennan Kellaris; Keller, Keith; Feil, William S.; Feil, Helene; Trong, Stephan; Di Bartolo, Genevieve; Lapidus, Alla

    2008-11-17

    Initial interest in Dechloromonas aromatica strain RCB arose from its ability to anaerobically degrade benzene. It is also able to reduce perchlorate and oxidize chlorobenzoate, toluene, and xylene, creating interest in using this organism for bioremediation. Little physiological data has been published for this microbe. It is considered to be a free-living organism. The a priori prediction that the D. aromatica genome would contain previously characterized 'central' enzymes involved in anaerobic aromatic degradation proved to be false, suggesting the presence of novel anaerobic aromatic degradation pathways in this species. These missing pathways include the benzyl succinyl synthase (bssABC) genes (responsible for formate addition to toluene) and the central benzoylCoA pathway for monoaromatics. In depth analyses using existing TIGRfam, COG, and InterPro models, and the creation of de novo HMM models, indicate a highly complex lifestyle with a large number of environmental sensors and signaling pathways, including a relatively large number of GGDEF domain signal receptors and multiple quorum sensors. A number of proteins indicate interactions with an as yet unknown host, as indicated by the presence of predicted cell host remodeling enzymes, effector enzymes, hemolysin-like proteins, adhesins, NO reductase, and both type III and type VI secretory complexes. Evidence of biofilm formation including a proposed exopolysaccharide complex with the somewhat rare exosortase (epsH), is also present. Annotation described in this paper also reveals evidence for several metabolic pathways that have yet to be observed experimentally, including a sulphur oxidation (soxFCDYZAXB) gene cluster, Calvin cycle enzymes, and nitrogen fixation (including RubisCo, ribulose-phosphate 3-epimerase, and nif gene families, respectively). Analysis of the D. aromatica genome indicates there is much to be learned regarding the metabolic capabilities, and life-style, for this microbial

  20. Willapa - Spartina Mapping and Eradication 2015

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — The Willapa National Wildlife Refuge (Willapa NWR) continues to work toward the eradication of the non-native cordgrass, Spartina alterniflora (Spartina) from...

  1. Willapa - Spartina Mapping and Eradication 2014

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — The Willapa National Wildlife Refuge (Willapa NWR) continued a successful program aimed at eradicating the non-native cordgrass, Spartina alterniflora (Spartina)...

  2. Poverty Eradication Dilemma: Understanding Poverty Dynamics in ...

    African Journals Online (AJOL)

    sulaiman.adebowale

    2008-10-20

    Oct 20, 2008 ... dilemma using the Poverty Eradication Action Plan (PEAP), an all-inclusive ... security, conflict resolution and disaster management; (iv) good .... modernization and industrialization even if it has meant forest, schools and.

  3. Roles of reactive chlorine species in trimethoprim degradation in the UV/chlorine process: Kinetics and transformation pathways.

    Science.gov (United States)

    Wu, Zihao; Fang, Jingyun; Xiang, Yingying; Shang, Chii; Li, Xuchun; Meng, Fangang; Yang, Xin

    2016-11-01

    The UV/chlorine process, which forms several reactive species including hydroxyl radicals (HO) and reactive chlorine species (RCS) to degrade contaminants, is being considered to be an advanced oxidation process. This study investigated the kinetics and mechanism of the degradation of trimethoprim (TMP) by the UV/chlorine process. The degradation of TMP was much faster by UV/chlorine compared to UV/H2O2. The degradation followed pseudo first-order kinetics, and the rate constant (k') increased linearly as the chlorine dosage increased from 20 μM to 200 μM and decreased as pH rose from 6.1 to 8.8. k' was not affected by chloride and bicarbonate but decreased by 50% in the presence of 1-mg/L NOM. The contribution of RCS, including Cl, Cl2(-) and ClO, to the degradation removal rate was much higher than that of HO and increased from 67% to 87% with increasing pH from 6.1 to 8.8 under the experimental condition. The increasing contribution of RCS to the degradation with increasing pH was attributable to the increase in the ClO concentration. Kinetic modeling and radical scavenging tests verified that ClO mainly attacked the trimethoxybenzyl moiety of TMP. RCS reacted with TMP much faster than HOCl/OCl(-) to form chlorinated products (i.e., m/z 325) and chlorinated disinfection byproducts such as chloroform, chloral hydrate, dichloroacetonitrile and trichloronitromethane. The hydroxylation and demethylation of m/z 325 driven by HO generated m/z 327 and m/z 341. Meanwhile, reactions of m/z 325 with HO and RCS/HOCl/OCl(-) generated dichlorinated and hydroxylated products (i.e., m/z 377). All the chlorinated products could be further depleted to produce products with less degree of halogenation in the UV/chlorine process, compared to dark chlorination. The acute toxicity to Vibrio fischeri by UV/chlorine was lower than chlorination at the same removal rate of TMP. This study demonstrated the importance of RCS, in particular, ClO, in the degradation of micropollutants

  4. Eradication of Ebola Based on Dynamic Programming

    Science.gov (United States)

    Zhu, Jia-Ming; Wang, Lu; Liu, Jia-Bao

    2016-01-01

    This paper mainly studies the eradication of the Ebola virus, proposing a scientific system, including three modules for the eradication of Ebola virus. Firstly, we build a basic model combined with nonlinear incidence rate and maximum treatment capacity. Secondly, we use the dynamic programming method and the Dijkstra Algorithm to set up M-S (storage) and several delivery locations in West Africa. Finally, we apply the previous results to calculate the total cost, production cost, storage cost, and shortage cost. PMID:27313655

  5. A Research Agenda for Malaria Eradication: Vaccines

    OpenAIRE

    ,

    2011-01-01

    Vaccines could be a crucial component of efforts to eradicate malaria. Current attempts to develop malaria vaccines are primarily focused on Plasmodium falciparum and are directed towards reducing morbidity and mortality. Continued support for these efforts is essential, but if malaria vaccines are to be used as part of a repertoire of tools for elimination or eradication of malaria, they will need to have an impact on malaria transmission. We introduce the concept of “vaccines that interrupt...

  6. Which factors affect the success or failure of eradication campaigns against alien species?

    Directory of Open Access Journals (Sweden)

    Therese Pluess

    Full Text Available Although issues related to the management of invasive alien species are receiving increasing attention, little is known about which factors affect the likelihood of success of management measures. We applied two data mining techniques, classification trees and boosted trees, to identify factors that relate to the success of management campaigns aimed at eradicating invasive alien invertebrates, plants and plant pathogens. We assembled a dataset of 173 different eradication campaigns against 94 species worldwide, about a half of which (50.9% were successful. Eradications in man-made habitats, greenhouses in particular, were more likely to succeed than those in (semi-natural habitats. In man-made habitats the probability of success was generally high in Australasia, while in Europe and the Americas it was higher for local infestations that are easier to deal with, and for international campaigns that are likely to profit from cross-border cooperation. In (semi- natural habitats, eradication campaigns were more likely to succeed for plants introduced as an ornamental and escaped from cultivation prior to invasion. Averaging out all other factors in boosted trees, pathogens, bacteria and viruses were most, and fungi the least likely to be eradicated; for plants and invertebrates the probability was intermediate. Our analysis indicates that initiating the campaign before the extent of infestation reaches the critical threshold, starting to eradicate within the first four years since the problem has been noticed, paying special attention to species introduced by the cultivation pathway, and applying sanitary measures can substantially increase the probability of eradication success. Our investigations also revealed that information on socioeconomic factors, which are often considered to be crucial for eradication success, is rarely available, and thus their relative importance cannot be evaluated. Future campaigns should carefully document

  7. Which factors affect the success or failure of eradication campaigns against alien species?

    Science.gov (United States)

    Pluess, Therese; Jarošík, Vojtěch; Pyšek, Petr; Cannon, Ray; Pergl, Jan; Breukers, Annemarie; Bacher, Sven

    2012-01-01

    Although issues related to the management of invasive alien species are receiving increasing attention, little is known about which factors affect the likelihood of success of management measures. We applied two data mining techniques, classification trees and boosted trees, to identify factors that relate to the success of management campaigns aimed at eradicating invasive alien invertebrates, plants and plant pathogens. We assembled a dataset of 173 different eradication campaigns against 94 species worldwide, about a half of which (50.9%) were successful. Eradications in man-made habitats, greenhouses in particular, were more likely to succeed than those in (semi-)natural habitats. In man-made habitats the probability of success was generally high in Australasia, while in Europe and the Americas it was higher for local infestations that are easier to deal with, and for international campaigns that are likely to profit from cross-border cooperation. In (semi-) natural habitats, eradication campaigns were more likely to succeed for plants introduced as an ornamental and escaped from cultivation prior to invasion. Averaging out all other factors in boosted trees, pathogens, bacteria and viruses were most, and fungi the least likely to be eradicated; for plants and invertebrates the probability was intermediate. Our analysis indicates that initiating the campaign before the extent of infestation reaches the critical threshold, starting to eradicate within the first four years since the problem has been noticed, paying special attention to species introduced by the cultivation pathway, and applying sanitary measures can substantially increase the probability of eradication success. Our investigations also revealed that information on socioeconomic factors, which are often considered to be crucial for eradication success, is rarely available, and thus their relative importance cannot be evaluated. Future campaigns should carefully document socioeconomic factors to

  8. Unique nonstructural proteins of Pneumonia Virus of Mice (PVM) promote degradation of interferon (IFN) pathway components and IFN-stimulated gene proteins.

    Science.gov (United States)

    Dhar, Jayeeta; Barik, Sailen

    2016-12-01

    Pneumonia Virus of Mice (PVM) is the only virus that shares the Pneumovirus genus of the Paramyxoviridae family with Respiratory Syncytial Virus (RSV). A deadly mouse pathogen, PVM has the potential to serve as a robust animal model of RSV infection, since human RSV does not fully replicate the human pathology in mice. Like RSV, PVM also encodes two nonstructural proteins that have been implicated to suppress the IFN pathway, but surprisingly, they exhibit no sequence similarity with their RSV equivalents. The molecular mechanism of PVM NS function, therefore, remains unknown. Here, we show that recombinant PVM NS proteins degrade the mouse counterparts of the IFN pathway components. Proteasomal degradation appears to be mediated by ubiquitination promoted by PVM NS proteins. Interestingly, NS proteins of PVM lowered the levels of several ISG (IFN-stimulated gene) proteins as well. These results provide a molecular foundation for the mechanisms by which PVM efficiently subverts the IFN response of the murine cell. They also reveal that in spite of their high sequence dissimilarity, the two pneumoviral NS proteins are functionally and mechanistically similar.

  9. Water deficit induces chlorophyll degradation via the 'PAO/phyllobilin' pathway in leaves of homoio- (Craterostigma pumilum) and poikilochlorophyllous (Xerophyta viscosa) resurrection plants.

    Science.gov (United States)

    Christ, Bastien; Egert, Aurélie; Süssenbacher, Iris; Kräutler, Bernhard; Bartels, Dorothea; Peters, Shaun; Hörtensteiner, Stefan

    2014-11-01

    Angiosperm resurrection plants exhibit poikilo- or homoiochlorophylly as a response to water deficit. Both strategies are generally considered as effective mechanisms to reduce oxidative stress associated with photosynthetic activity under water deficiency. The mechanism of water deficit-induced chlorophyll (Chl) degradation in resurrection plants is unknown but has previously been suggested to occur as a result of non-enzymatic photooxidation. We investigated Chl degradation during dehydration in both poikilochlorophyllous (Xerophyta viscosa) and homoiochlorophyllous (Craterostigma pumilum) species. We demonstrate an increase in the abundance of PHEOPHORBIDE a OXYGENASE (PAO), a key enzyme of Chl breakdown, together with an accumulation of phyllobilins, that is, products of PAO-dependent Chl breakdown, in both species. Phyllobilins and PAO levels diminished again in leaves from rehydrated plants. We conclude that water deficit-induced poikilochlorophylly occurs via the well-characterized PAO/phyllobilin pathway of Chl breakdown and that this mechanism also appears conserved in a resurrection species displaying homoiochlorophylly. The roles of the PAO/phyllobilin pathway during different plant developmental processes that involve Chl breakdown, such as leaf senescence and desiccation, fruit ripening and seed maturation, are discussed. © 2014 John Wiley & Sons Ltd.

  10. Degradation pathways of aniline in aqueous solutions during electro-oxidation with BDD electrodes and UV/H2O2 treatment.

    Science.gov (United States)

    Benito, Aleix; Penadés, Aida; Lliberia, Josep Lluis; Gonzalez-Olmos, Rafael

    2017-01-01

    In this work, it has been studied the mineralization of aniline, a toxic substance of low biodegradability typically found in many industrial wastewaters, through electro-oxidation using boron doped diamond (BDD) electrodes and photo-oxidation (UV photolysis and UV/H2O2 treatments). It was observed that in electro-oxidation and UV/H2O2, it was feasible to reach aniline mineralizations higher than 85%. Two different degradation routes have been observed during the aniline oxidation in these two treatments. The first route was the mineralization pathway, in which aniline was oxidized to CO2, water and nitrate. The second route was the polyaniline pathway in which polyanilines of high molecular weight are formed. The intermediate compounds involved in both degradation routes are different depending on the treatment used. In the electro-oxidation, denitrification processes were also observed. From an economical point of view, electro-oxidation of aniline using BDD electrodes is more interesting than UV/H2O2 due it has an 87% lower operational cost. So, electro-oxidation using BDD electrodes seems to be a more suitable technique for the mineralization of wastewater containing aniline than UV or H2O2 based technologies.

  11. Degradation of 2,4-dihydroxibenzoic acid by vacuum UV process in aqueous solution: Kinetic, identification of intermediates and reaction pathway

    Energy Technology Data Exchange (ETDEWEB)

    Azrague, Kamal [Laboratoire IMRCP, CNRS UMR 5623, University of Toulouse, 118 route de Narbonne, 31062 Toulouse (France); Department for Water and Environment, SINTEF, Klaebuveien 153, Trondheim 7465 (Norway); Pradines, Vincent; Bonnefille, Eric [Laboratoire IMRCP, CNRS UMR 5623, University of Toulouse, 118 route de Narbonne, 31062 Toulouse (France); Laboratoire LCC, CNRS, 205 route de Narbonne, F31077 Toulouse Cedex 4 (France); Claparols, Catherine [Laboratoire LCC, CNRS, 205 route de Narbonne, F31077 Toulouse Cedex 4 (France); Universite de Toulouse, UPS, Service Commun de Spectrometrie de Masse, 118 route de Narbonne, F31062 Toulouse Cedex 9 (France); Maurette, Marie-Therese [Laboratoire IMRCP, CNRS UMR 5623, University of Toulouse, 118 route de Narbonne, 31062 Toulouse (France); Benoit-Marquie, Florence, E-mail: florence@chimie.ups-tlse.fr [Laboratoire IMRCP, CNRS UMR 5623, University of Toulouse, 118 route de Narbonne, 31062 Toulouse (France)

    2012-10-30

    Highlights: Black-Right-Pointing-Pointer Degradation of 2,4-dihydroxybenzoic acid (DHBA) by vacuum UV photolysis of water. Black-Right-Pointing-Pointer V-UV Xe-excimer lamps produced essentially hydroxyl radicals (HO Degree-Sign ). Black-Right-Pointing-Pointer Identification of all intermediates formed allowed us to propose a reaction pathway. Black-Right-Pointing-Pointer This reaction pathway showed that DHBA reacts differently with HO Degree-Sign and h+. Black-Right-Pointing-Pointer DHBA would be used as a probe to determine which of these entities were involved. - Abstract: 2,4-Dihydroxybenzoic acid (2,4-DHBA) is found frequently as a pollutant in natural waters and represents a threat to water quality because it is a precursor to the formation of quinones which are highly toxic. The degradation of 2,4-DHBA using the vacuum UV photolysis of water has been investigated. Irradiation was carried out in an annular photoreactor equipped with a Xe-excimer lamp situated in the centre and emitting at 172 nm. The degradation kinetic followed a pseudo first order and the reaction has been found to be very heterogeneous, especially at low concentration. Impacts of oxygen or temperature have also been investigated but no effect has been shown. LC-MS and HPLC-UV combined with other analytical techniques allowed the identification of the formation of trihydroxybenzoiec acids and trihydroxybenzenes which underwent a ring opening, conducting to the formation of aliphatic products named {alpha}, {beta}, {delta} and {gamma}. These products were in turn degraded successively into maleiec acid, malic and succinic acid, malonic acid, glyoxalic acid and oxalic acid before reaching the complete mineralization in about 180 min. The proposed reaction pathway has shown to be very different from the one observed for the TiO{sub 2} photocatalysis which involves only holes (h{sup +}) without any formation of aromatic intermediates. The different behaviours of 2,4-DHBA towards the h

  12. A calmodulin-like protein suppresses RNA silencing and promotes geminivirus infection by degrading SGS3 via the autophagy pathway in Nicotiana benthamiana

    Science.gov (United States)

    Li, Fangfang; Zhao, Nan; Xu, Xiongbiao; Wang, Yaqin; Yang, Xiuling; Liu, Shu-Sheng; Wang, Aiming; Zhou, Xueping

    2017-01-01

    A recently characterized calmodulin-like protein is an endogenous RNA silencing suppressor that suppresses sense-RNA induced post-transcriptional gene silencing (S-PTGS) and enhances virus infection, but the mechanism underlying calmodulin-like protein-mediated S-PTGS suppression is obscure. Here, we show that a calmodulin-like protein from Nicotiana benthamiana (NbCaM) interacts with Suppressor of Gene Silencing 3 (NbSGS3). Deletion analyses showed that domains essential for the interaction between NbSGS3 and NbCaM are also required for the subcellular localization of NbSGS3 and NbCaM suppressor activity. Overexpression of NbCaM reduced the number of NbSGS3-associated granules by degrading NbSGS3 protein accumulation in the cytoplasm. This NbCaM-mediated NbSGS3 degradation was sensitive to the autophagy inhibitors 3-methyladenine and E64d, and was compromised when key autophagy genes of the phosphatidylinositol 3-kinase (PI3K) complex were knocked down. Meanwhile, silencing of key autophagy genes within the PI3K complex inhibited geminivirus infection. Taken together these data suggest that NbCaM acts as a suppressor of RNA silencing by degrading NbSGS3 through the autophagy pathway. PMID:28212430

  13. Biodegradation of RDX and MNX with Rhodococcus sp. Strain DN22: New Insights into the Degradation Pathway

    Science.gov (United States)

    2010-11-15

    ENVIRONMENTAL SCIENCE & TECHNOLOGY / VOL. 44, NO. 24, 2010 10.1021/es1023724  2010 American Chemical Society Published on Web 11/24/2010 Report...exclusively; how- FIGURE 1. Time course of aerobic biodegradation of RDX with Rhodococcus sp. DN22 VOL. 44, NO. 24, 2010 / ENVIRONMENTAL SCIENCE & TECHNOLOGY 9...water (H216O) (C) or H218O (D). 9332 9 ENVIRONMENTAL SCIENCE & TECHNOLOGY / VOL. 44, NO. 24, 2010 Degradation of MNX with Rhodococcus sp. strain

  14. The dominant acetate degradation pathway/methanogenic composition in full-scale anaerobic digesters operating under different ammonia levels

    DEFF Research Database (Denmark)

    Fotidis, Ioannis; Karakashev, Dimitar Borisov; Angelidaki, Irini

    2014-01-01

    Ammonia is a major environmental factor influencing biomethanation in full-scale anaerobic digesters. In this study, the effect of different ammonia levels on methanogenic pathways and methanogenic community composition of full-scale biogas plants was investigated. Eight full-scale digesters...... operating under different ammonia levels were sampled, and the residual biogas production was followed in fed-batch reactors. Acetate, labelled in the methyl group, was used to determine the methanogenic pathway by following the 14CH4 and 14CO2 production. Fluorescence in situ hybridisation was used...

  15. HUWE1 interacts with BRCA1 and promotes its degradation in the ubiquitin–proteasome pathway (Biochemical and Biophysical Research Communications, v. 444, isse 4)

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Xiaozhen [Department of Cell Biology, Peking University Health Science Center, Beijing 100191 (China); Institute of Systems Biology, Peking University, Beijing 100191 (China); Lu, Guang; Li, Li; Yi, Juan; Yan, Kaowen; Wang, Yaqing; Zhu, Baili; Kuang, Jingyu; Lin, Ming; Zhang, Sha [Department of Cell Biology, Peking University Health Science Center, Beijing 100191 (China); Shao, Genze, E-mail: gzshao@bjmu.edu.cn [Department of Cell Biology, Peking University Health Science Center, Beijing 100191 (China); Institute of Systems Biology, Peking University, Beijing 100191 (China)

    2014-02-21

    Highlights: • The 2000–2634aa region of HUWE1 mediates the interaction with BRCA1 degron. • HUWE1 promotes the degradation of BRCA1 through the ubiquitin–proteasome pathway. • HUWE1 expression is inversely correlated with BRCA1 in breast cancer cells. • RNAi inhibition of HUWE1 confers increased resistance of MCF-10F cells to IR and MMC. - Abstract: The cellular BRCA1 protein level is essential for its tumor suppression activity and is tightly regulated through multiple mechanisms including ubiquitn–proteasome system. E3 ligases are involved to promote BRCA1 for ubiquitination and degradation. Here, we identified HUWE1/Mule/ARF-BP1 as a novel BRCA1-interacting protein involved in the control of BRCA1 protein level. HUWE1 binds BRCA1 through its N-terminus degron domain. Depletion of HUWE1 by siRNA-mediated interference significantly increases BRCA1 protein levels and prolongs the half-life of BRCA1. Moreover, exogenous expression of HUWE1 promotes BRCA1 degradation through the ubiquitin–proteasome pathway, which could explain an inverse correlation between HUWE1 and BRCA1 levels in MCF10F, MCF7 and MDA-MB-231 breast cancer cells. Consistent with a functional role for HUWE1 in regulating BRCA1-mediated cellular response to DNA damage, depletion of HUWE1 by siRNA confers increased resistance to ionizing radiation and mitomycin. These data indicate that HUWE1 is a critical negative regulator of BRCA1 and suggest a new molecular mechanism for breast cancer pathogenesis.

  16. HUWE1 interacts with BRCA1 and promotes its degradation in the ubiquitin–proteasome pathway (Biochemical and Biophysical Research Communications, v. 444 issue 3)

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Xiaozhen [Department of Cell Biology, Peking University Health Science Center, Beijing 100191 (China); Institute of Systems Biology, Peking University, Beijing 100191 (China); Lu, Guang; Li, Li; Yi, Juan; Yan, Kaowen; Wang, Yaqing; Zhu, Baili; Kuang, Jingyu; Lin, Ming; Zhang, Sha [Department of Cell Biology, Peking University Health Science Center, Beijing 100191 (China); Shao, Genze, E-mail: gzshao@bjmu.edu.cn [Department of Cell Biology, Peking University Health Science Center, Beijing 100191 (China); Institute of Systems Biology, Peking University, Beijing 100191 (China)

    2014-02-14

    Highlights: • The 2000–2634 aa region of HUWE1 mediates the interaction with BRCA1 degron. • HUWE1 promotes the degradation of BRCA1 through the ubiquitin–proteasome pathway. • HUWE1 expression is inversely correlated with BRCA1 in breast cancer cells. • RNAi inhibition of HUWE1 confers increased resistance of MCF-10F cells to IR and MMC. - Abstract: The cellular BRCA1 protein level is essential for its tumor suppression activity and is tightly regulated through multiple mechanisms including ubiquitn–proteasome system. E3 ligases are involved to promote BRCA1 for ubiquitination and degradation. Here, we identified HUWE1/Mule/ARF-BP1 as a novel BRCA1-interacting protein involved in the control of BRCA1 protein level. HUWE1binds BRCA1 through its N-terminus degron domain. Depletion of HUWE1 by siRNA-mediated interference significantly increases BRCA1 protein levels and prolongs the half-life of BRCA1. Moreover, exogenous expression of HUWE1 promotes BRCA1 degradation through the ubiquitin–proteasome pathway, which could explain an inverse correlation between HUWE1 and BRCA1 levels in MCF10F, MCF7 and MDA-MB-231 breast cancer cells. Consistent with a functional role for HUWE1 in regulating BRCA1-mediated cellular response to DNA damage, depletion of HUWE1 by siRNA confers increased resistance to ionizing radiation and mitomycin. These data indicate that HUWE1 is a critical negative regulator of BRCA1 and suggest a new molecular mechanism for breast cancer pathogenesis.

  17. Potentiality of yeast Candida sp. SMN04 for degradation of cefdinir, a cephalosporin antibiotic: kinetics, enzyme analysis and biodegradation pathway.

    Science.gov (United States)

    Selvi, A; Das, Devlina; Das, Nilanjana

    2015-01-01

    A new yeast strain isolated from the pharmaceutical wastewater was capable of utilizing cefdinir as a sole carbon source for their growth in mineral medium. The yeast was identified and named as Candida sp. SMN04 based on morphology and 18S-ITS-D1/D2/D3 rRNA sequence analysis. The interaction between factors pH (3.0-9.0), inoculum dosage (1-7%), time (1-11 day) and cefdinir concentration (50-450 mg/L) was studied using a Box-Behnken design. The factors were studied as a result of their effect on cell dry weight (R1; g/L), extended spectrum β-lactamase (ESBL) assay (R2; mm), P450 activity (R3; U/mL) and degradation (R4; %). Maximum values of R1, R2, R3 and R4 were obtained at central values of all the parameters. The isolated yeast strain efficiently degraded 84% of 250 mg L⁻¹ of cefdinir within 6 days with a half-life of 2.97 days and degradation rate constant of 0.2335 per day. Pseudo-first-order model efficiently described the process. Among the various enzymes tested, the order of activity at the end of Day 4 was noted to be: cytochrome P450 (1.76 ± 0.03) > NADPH reductase (1.51 ± 0.20) > manganese peroxidase and amylase (0.66 ± 0.15; 0.66 ± 0.70). Intermediates were successfully characterized by liquid chromatography-mass spectrometry. The opening of the β-lactam ring involving ESBL activity was considered as one of the major steps in the cefdinir degradation process. Fourier transform-infrared spectroscopy analysis showed the absence of spectral vibrations between 1766 and 1519 cm⁻¹ confirming the complete removal of lactam ring during cefdinir degradation. The results of the present study are promising for the use of isolated yeast Candida sp. SMN04 as a potential bioremediation agent.

  18. Eradication of measles: remaining challenges.

    Science.gov (United States)

    Holzmann, Heidemarie; Hengel, Hartmut; Tenbusch, Matthias; Doerr, H W

    2016-06-01

    , epidemiological and virological surveillance by the use of modern laboratory diagnostics and reporting systems. By consequent implementation of carefully designed epidemiologic and prophylactic measures, it should be possible to eradicate MeV globally out of mankind, as the closely related morbillivirus of rinderpest could be successfully eliminated out of the cattle on a global scale.

  19. Biodegradation of octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) by Phanerochaete chrysosporium: new insight into the degradation pathway.

    Science.gov (United States)

    Fournier, Diane; Halasz, Annamaria; Thiboutot, Sonia; Ampleman, Guy; Manno, Dominic; Hawari, Jalal

    2004-08-01

    Octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) is a recalcitrant energetic chemical that tends to accumulate in soil, close to the surface. The present study describes the aerobic biodegradability of HMX using Phanerochaete chrysosporium. When added to 7 day old static P. chrysosporium liquid cultures, HMX (600 nmol) degraded within 25 days of incubation. The removal of HMX was concomitant with the formation of transient amounts of its mono-nitroso derivative (1-NO-HMX). The latter apparently degraded via two potential routes: the first involved N-denitration followed by hydrolytic ring cleavage, and the second involved alpha-hydroxylation prior to ring cleavage. The degradation of 1-NO-HMX gave the ring-cleavage product 4-nitro-2,4-diazabutanal (NDAB), nitrite (NO2 -), nitrous oxide (N2O), and formaldehyde (HCHO). Using [14C]-HMX, we obtained 14CO2 (70% in 50 days), representing three C atoms of HMX. Incubation of real soils, contaminated with either HMX (403 micromol kg(-1)) (military base soil) or HMX (3057 micromol kg(-1)), and RDX (342 micromol kg(-1)) (ammunition soil) with the fungus led to 75 and 19.8% mineralization of HMX (liberated 14CO2), respectively, also via the intermediary formation of 1-NO-HMX. Mineralization in the latter soil increased to 35% after the addition of glucose, indicating that a fungus-based remediation process for heavily contaminated soils is promising. The present findings improve our understanding about the degradation pathway of HMX and demonstrate the utility of using the robust and versatile fungus P. chrysosporium to develop effective remediation processes for the removal of HMX.

  20. Synthesized TiO2/ZSM-5 composites used for the photocatalytic degradation of azo dye: Intermediates, reaction pathway, mechanism and bio-toxicity

    Science.gov (United States)

    Zhou, Kefu; Hu, Xin-Yan; Chen, Bor-Yann; Hsueh, Chung-Chuan; Zhang, Qian; Wang, Jiajie; Lin, Yu-Jung; Chang, Chang-Tang

    2016-10-01

    In this study, a one-step solid dispersion method was used to synthesize titanium dioxide (TiO2)/Zeolite Socony Mobil-5 (ZSM-5) composites with substantially reduced time and energy consumption. A degradation efficiency of more than 95% was achieved within 10 min using 50% PTZ (synthesized TiO2/ZSM-5 composites with TiO2 contents of 50 wt% loaded on ZSM-5) at pH 7 and 25 °C. The possible degradation pathway of azo-dye Reactive Black 5 (RB5) was investigated using gas chromatography-mass spectrometry and ion chromatography (IC). The bonds between the N atoms and naphthalene groups are likely attacked first and cleaved by hydroxyl radicals, ultimately resulting in the decolorization and mineralization of the azo dye. A comparative assessment of the characteristics of abiotic and biotic dye decolorization was completed. In addition, the toxicity effects of the degradation intermediates of azo-dye RB5 on cellular respiratory activity were analyzed. The bio-toxicity results showed that the decay rate constants of CO2 production from the azo-dye RB5 samples at different degradation times increased initially and subsequently decreased, indicating that intermediates of higher toxicity could adhere to the catalyst surface and gradually destroyed by further photocatalytic oxidation. Additionally, EDTA (hole scavengers) and t-BuOH (radical scavengers) were used to detect the main active oxidative species in the system. The results showed that the hydroxyl radicals are the main oxidation species in the photocatalytic process.

  1. Degradation characteristics and identification and the degradation pathway of the atrazine-degrading strain DNS32%阿特拉津降解菌株DNS32的降解特性及分类鉴定与降解途径研究

    Institute of Scientific and Technical Information of China (English)

    郭火生; 王志刚; 孟冬芳; 王洋; 张庆媛; 张颖

    2012-01-01

    [Objective] The objective was to study the identification, degradation characteristics and the degradation pathway of the atrazine-degrading strain DNS32, and enrich the resources of atrazine-degrading bacteria. [Methods] Strain DNS32, which was isolated from black soil in this study, could utilize atrazine as the sole nitrogen source for growth, and its basic degradation characteristics were studied. The 16S rRNA gene phylogenetic analysis was used to identify of the strain DNS32. The degradation pathway was studied by degrading genes amplification and the measurement of the content of the final catabolite. [Results] The results showed that strain DNS32 had greater degradation capacity and could utilize certain amount of atrazine even under a relative low temperature. The 16S rRNA gene phylogenetic analysis showed that the 16S rRNA gene sequence of the strain DNS32 had a 99% similarity with that of Acinetobacter lwoffii. Atrazine-degrading genes trzN, atzB and atzC were amplified by PCR, and these genes enabled strain DNS32 decompose atrazine to cyanuric acid, in accordance with the degradation pathway of Arthrobacter aurescens TC1 proved by the measurement of the atrazine degradation rate and the content of the final catabolite. [Conclusion] This study enriched the resources of atrazine-degrading bacteria and provided useful informations to the study of the atrazine-degrading strains belonging to Acinetobacter.%[目的]研究阿特拉津降解菌株DNS32的菌种分类、降解特性及降解途径,丰富阿特拉津降解菌菌种资源.[方法]在长期施用阿特拉津的东北地区寒地黑土中筛选出一株以阿特拉津为唯一氮源生长的降解菌株DNS32,测定其基本降解特性,通过16SrRNA序列分析进行分类鉴定,并利用阿特拉津降解基因PCR扩增技术及降解产物生成量的测定,进一步揭示其降解途径.[结果]实验结果发现DNS32菌株具有较好的降解能力,且在相对较低温度下

  2. Helicobacter pylori eradication for preventing gastric cancer.

    Science.gov (United States)

    Lu, Bin; Li, Meng

    2014-05-21

    Helicobacter pylori (H. pylori) infection is a major risk factor for gastric cancer (GC) development, which is one of the most challenging malignant diseases worldwide with limited treatments. In the multistep pathogenesis of GC, H. pylori infection slowly induces chronic active gastritis, which progresses through the premalignant stages of atrophic gastritis, intestinal metaplasia, and dysplasia, and then finally to GC. Although eradication of H. pylori is a reasonable approach for the prevention of GC, there have been some contradictory reports, with only some long-term follow-up data showing efficacy of this approach. The inconsistencies are likely due to the insufficient number of participants, relatively short follow-up periods, poor quality of study designs, and the degree and extent of preneoplastic changes at the time of H. pylori eradication. This review analyzes recent high-quality studies to resolve the discrepancies regarding the eradication of H. pylori for GC prevention. The relationship between H. pylori eradication and GC/precancerous lesions/metachronous GC is examined, and the cost-effectiveness of this strategy in the prevention of GC is assessed. Although it is assumed that eradication of H. pylori has the potential to prevent GC, the feasibility and appropriate timing of this strategy for cancer prevention remain to be determined. As a result, additional well-designed trials with longer follow-up periods are needed to clarify this issue.

  3. Murrayafoline A attenuates the Wnt/{beta}-catenin pathway by promoting the degradation of intracellular {beta}-catenin proteins

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Hyuk; Gwak, Jungsug; Cho, Munju; Ryu, Min-Jung [PharmacoGenomics Research Center, Inje University, Busan 614-735 (Korea, Republic of); Lee, Jee-Hyun; Kim, Sang Kyum; Kim, Young Ho [College of Pharmacy, Chungnam National University, Daejeon 305-764 (Korea, Republic of); Lee, Gye Won [Department of Pharmaceutical Engineering, Konyang University, Nonsan 320-711 (Korea, Republic of); Yun, Mi-Young [Department of Beauty Health Care, Daejeon University, Daejeon 305-764 (Korea, Republic of); Cuong, Nguyen Manh [Institute of Natural Products Chemistry, Vietnam Academy of Science and Technology, Hanoi (Viet Nam); Shin, Jae-Gook [PharmacoGenomics Research Center, Inje University, Busan 614-735 (Korea, Republic of); Song, Gyu-Yong, E-mail: gysong@cnu.ac.kr [College of Pharmacy, Chungnam National University, Daejeon 305-764 (Korea, Republic of); Oh, Sangtaek, E-mail: ohsa@inje.ac.kr [PharmacoGenomics Research Center, Inje University, Busan 614-735 (Korea, Republic of)

    2010-01-01

    Molecular lesions in Wnt/{beta}-catenin signaling and subsequent up-regulation of {beta}-catenin response transcription (CRT) occur frequently during the development of colon cancer. To identify small molecules that suppress CRT, we screened natural compounds in a cell-based assay for detection of TOPFalsh reporter activity. Murrayafoline A, a carbazole alkaloid isolated from Glycosmis stenocarpa, antagonized CRT that was stimulated by Wnt3a-conditioned medium (Wnt3a-CM) or LiCl, an inhibitor of glycogen synthase kinase-3{beta} (GSK-3{beta}), and promoted the degradation of intracellular {beta}-catenin without altering its N-terminal phosphorylation at the Ser33/37 residues, marking it for proteasomal degradation, or the expression of Siah-1, an E3 ubiquitin ligase. Murrayafoline A repressed the expression of cyclin D1 and c-myc, which is known {beta}-catenin/T cell factor (TCF)-dependent genes and thus inhibited the proliferation of various colon cancer cells. These findings indicate that murrayafoline A may be a potential chemotherapeutic agent for use in the treatment of colon cancer.

  4. Carbofuran removal in continuous-photocatalytic reactor: Reactor optimization, rate-constant determination and carbofuran degradation pathway analysis.

    Science.gov (United States)

    Vishnuganth, M A; Remya, Neelancherry; Kumar, Mathava; Selvaraju, N

    2017-02-22

    Carbofuran (CBF) removal in a continuous-flow photocatalytic reactor with granular activated carbon supported titanium dioxide (GAC-TiO2) catalyst was investigated. The effects of feed flow rate, TiO2 concentration and addition of supplementary oxidants on CBF removal were investigated. The central composite design (CCD) was used to design the experiments and to estimate the effects of feed flow rate and TiO2 concentration on CBF removal. The outcome of CCD experiments demonstrated that reactor performance was influenced mainly by feed flow rate compared to TiO2 concentration. A second-order polynomial model developed based on CCD experiments fitted the experimental data with good correlation (R(2) ∼ 0.964). The addition of 1 mL min(-1) hydrogen peroxide has shown complete CBF degradation and 76% chemical oxygen demand removal under the following operating conditions of CBF ∼50 mg L(-1), TiO2 ∼5 mg L(-1) and feed flow rate ∼82.5 mL min(-1). Rate constant of the photodegradation process was also calculated by applying the kinetic data in pseudo-first-order kinetics. Four major degradation intermediates of CBF were identified using GC-MS analysis. As a whole, the reactor system and GAC-TiO2 catalyst used could be constructive in cost-effective CBF removal with no impact to receiving environment through getaway of photocatalyst.

  5. The human papillomavirus E6 oncogene represses a cell adhesion pathway and disrupts focal adhesion through degradation of TAp63β upon transformation.

    Directory of Open Access Journals (Sweden)

    Youcef Ben Khalifa

    2011-09-01

    Full Text Available Cervical carcinomas result from cellular transformation by the human papillomavirus (HPV E6 and E7 oncogenes which are constitutively expressed in cancer cells. The E6 oncogene degrades p53 thereby modulating a large set of p53 target genes as shown previously in the cervical carcinoma cell line HeLa. Here we show that the TAp63β isoform of the p63 transcription factor is also a target of E6. The p63 gene plays an essential role in skin homeostasis and is expressed as at least six isoforms. One of these isoforms, ΔNp63α, has been found overexpressed in squamous cell carcinomas and is shown here to be constitutively expressed in Caski cells associated with HPV16. We therefore explored the role of p63 in these cells by performing microarray analyses after repression of endogenous E6/E7 expression. Upon repression of the oncogenes, a large set of p53 target genes was found activated together with many p63 target genes related to cell adhesion. However, through siRNA silencing and ectopic expression of various p63 isoforms we demonstrated that TAp63β is involved in activation of this cell adhesion pathway instead of the constitutively expressed ΔNp63α and β. Furthermore, we showed in cotransfection experiments, combined with E6AP siRNA silencing, that E6 induces an accelerated degradation of TAp63β although not through the E6AP ubiquitin ligase used for degradation of p53. Repression of E6 transcription also induces stabilization of endogenous TAp63β in cervical carcinoma cells that lead to an increased concentration of focal adhesions at the cell surface. Consequently, TAp63β is the only p63 isoform suppressed by E6 in cervical carcinoma as demonstrated previously for p53. Down-modulation of focal adhesions through disruption of TAp63β therefore appears as a novel E6-dependent pathway in transformation. These findings identify a major physiological role for TAp63β in anchorage independent growth that might represent a new critical

  6. Carbazole-degradative IncP-7 plasmid pCAR1.2 is structurally unstable in Pseudomonas fluorescens Pf0-1, which accumulates catechol, the intermediate of the carbazole degradation pathway.

    Science.gov (United States)

    Takahashi, Yurika; Shintani, Masaki; Li, Li; Yamane, Hisakazu; Nojiri, Hideaki

    2009-06-01

    We determined the effect of the host on the function and structure of the nearly identical IncP-7 carbazole-degradative plasmids pCAR1.1 and pCAR1.2. We constructed Pseudomonas aeruginosa PAO1(pCAR1.2) and P. fluorescens Pf0-1Km(pCAR1.2) and compared their growth on carbazole- and succinate-containing media with that of P. putida KT2440(pCAR1.1). We also assessed the stability of the genetic structures of the plasmids in each of the three hosts. Pf0-1Km(pCAR1.2) showed dramatically delayed growth when carbazole was supplied as the sole carbon source, while the three strains grew at nearly the same rate on succinate. Among the carbazole-grown Pf0-1Km(pCAR1.2) cells, two types of deficient strains appeared and dominated the population; such dominance was not observed in the other two strains or for succinate-grown Pf0-1Km(pCAR1.2). Genetic analysis showed that the two deficient strains possessed pCAR1.2 derivatives in which the carbazole-degradative car operon was deleted or its regulatory gene, antR, was deleted by homologous recombination between insertion sequences. From genomic information and quantitative reverse transcription-PCR analyses of the genes involved in carbazole mineralization by Pf0-1Km(pCAR1.2), we found that the cat genes on the chromosome of Pf0-1Km, which are necessary for the degradation of catechol (a toxic intermediate in the carbazole catabolic pathway), were not induced in the presence of carbazole. The resulting accumulation of catechol may have enabled the strain that lost its carbazole-degrading ability to have overall higher fitness than the wild-type strain. These results suggest that the functions of the chromosomal genes contributed to the selection of plasmid derivatives with altered structures.

  7. Biological degradation of 4-chlorobenzoic acid by a PCB-metabolizing bacterium through a pathway not involving (chloro)catechol.

    Science.gov (United States)

    Adebusoye, Sunday A

    2017-02-01

    Cupriavidus sp. strain SK-3, previously isolated on polychlorinated biphenyl mixtures, was found to aerobically utilize a wide spectrum of substituted aromatic compounds including 4-fluoro-, 4-chloro- and 4-bromobenzoic acids as a sole carbon and energy source. Other chlorobenzoic acid (CBA) congeners such as 2-, 3-, 2,3-, 2,5-, 3,4- and 3,5-CBA were all rapidly transformed to respective chlorocatechols (CCs). Under aerobic conditions, strain SK-3 grew readily on 4-CBA to a maximum concentration of 5 mM above which growth became impaired and yielded no biomass. Growth lagged significantly at concentrations above 3 mM, however chloride elimination was stoichiometric and generally mirrored growth and substrate consumption in all incubations. Experiments with resting cells, cell-free extracts and analysis of metabolite pools suggest that 4-CBA was metabolized in a reaction exclusively involving an initial hydrolytic dehalogenation yielding 4-hydroxybenzoic acid, which was then hydroxylated to protocatechuic acid (PCA) and subsequently metabolized via the β-ketoadipate pathway. When strain SK-3 was grown on 4-CBA, there was gratuitous induction of the catechol-1,2-dioxygenase and gentisate-1,2-dioxygenase pathways, even if both were not involved in the metabolism of the acid. While activities of the modified ortho- and meta-cleavage pathways were not detectable in all extracts, activity of PCA-3,4-dioxygenase was over ten-times higher than those of catechol-1,2- and gentisate-1,2-dioxygenases. Therefore, the only reason other congeners were not utilized for growth was the accumulation of CCs, suggesting a narrow spectrum of the activity of enzymes downstream of benzoate-1,2-dioxygenase, which exhibited affinity for a number of substituted analogs, and that the metabolic bottlenecks are either CCs or catabolites of the modified ortho-cleavage metabolic route.

  8. Genetic Variation in the Histamine Production, Response, and Degradation Pathway Is Associated with Histamine Pharmacodynamic Response in Children with Asthma

    Science.gov (United States)

    Jones, Bridgette L.; Sherwin, Catherine M. T.; Liu, Xiaoxi; Dai, Hongying; Vyhlidal, Carrie A.

    2017-01-01

    Introduction: There is growing knowledge of the wide ranging effects of histamine throughout the body therefore it is important to better understand the effects of this amine in patients with asthma. We aimed to explore the association between histamine pharmacodynamic (PD) response and genetic variation in the histamine pathway in children with asthma. Methods: Histamine Iontophoresis with Laser Doppler Monitoring (HILD) was performed in children with asthma and estimates for area under the effect curve (AUEC), maximal response over baseline (Emax), and time of Emax (Tmax) were calculated using non-compartmental analysis and non-linear mixed-effects model with a linked effect PK/PD model. DNA isolation and genotyping were performed among participants to detect known single nucleotide polymorphisms (SNPs) (n = 10) among genes (HDC, HNMT, ABP1, HRH1, HRH4) within the histamine pathway. General linear model was used to identify associations between histamine related genetic variants and measured histamine PD response parameters. Results: Genotyping and HILD response profiles were completed for 163 children. ABP1 47 C/T, ABP1 4107, and HNMT-1639 C/Twere associated with Emax (ABP1 47 CC genotype mean Emax 167.21 vs. CT/TT genotype mean Emax 139.20, p = 0.04; ABP1 4107 CC genotype mean Emax 141.72 vs. CG/GG genotype mean Emax 156.09, p = 0.005; HNMT-1639 CC genotype mean Emax 132.62 vs. CT/TT genotype mean Emax 155.3, p = 0.02). In a stratified analysis among African American children only, ABP1 and HNMT SNPs were also associated with PD response; HRH4 413 CC genotype was associated with lower Emax, p = 0.009. Conclusions: We show for the first time that histamine pathway genetic variation is associated with measureable changes in histamine response in children with asthma. The variability in histamine response and impact of histamine pathway genotype is important to further explore in patients with asthma so as to improve disease phenotyping leading to more

  9. Yaws: towards the WHO eradication target

    Science.gov (United States)

    Marks, Michael

    2016-01-01

    In 2012 WHO declared a target to eradicate yaws by 2020. The cornerstone of this strategy is community mass treatment with azithromycin. Initial studies suggest this is a very effective tool that may be capable of interrupting transmission. Alongside this there has been progress in the development and validation of diagnostic tests for yaws. Several new challenges have also emerged, in particular, evidence that Haemophilus ducreyi can cause phenotypically similar ulcers in yaws endemic communities, and evidence for a possible non-human primate reservoir. The 2020 eradication target remains ambitious and more challenges should be expected on the journey. PMID:27268712

  10. Yaws: towards the WHO eradication target.

    Science.gov (United States)

    Marks, Michael

    2016-06-01

    In 2012 WHO declared a target to eradicate yaws by 2020. The cornerstone of this strategy is community mass treatment with azithromycin. Initial studies suggest this is a very effective tool that may be capable of interrupting transmission. Alongside this there has been progress in the development and validation of diagnostic tests for yaws. Several new challenges have also emerged, in particular, evidence that Haemophilus ducreyi can cause phenotypically similar ulcers in yaws endemic communities, and evidence for a possible non-human primate reservoir. The 2020 eradication target remains ambitious and more challenges should be expected on the journey.

  11. Global eradication of measles: Are we poised?

    Science.gov (United States)

    Kulkarni, Raghavendra D; Ajantha, G S; Kiran, Aithal R; Pravinchandra, K R

    2017-01-01

    Measles, a highly infectious viral disease is the next target for eradication following poliovirus. Decades of experience with highly effective vaccination has invigorated us to take on this virus. The task is not only Titanic but is laced with intricate issues. Recently, an outbreak of fever with rash occurred on a tertiary care teaching hospital campus and was confirmed serologically as measles outbreak by IgMELISA. Therefore, we searched the literature related to outbreaks, transmission of the measles virus, age groups involved, vaccination strategies, vaccination failure and epidemiological features of the disease and reviewed the possible reasons for such outbreaks and problems in the global eradication of the virus.

  12. Global eradication of measles: Are we poised?

    Directory of Open Access Journals (Sweden)

    Raghavendra D Kulkarni

    2017-01-01

    Full Text Available Measles, a highly infectious viral disease is the next target for eradication following poliovirus. Decades of experience with highly effective vaccination has invigorated us to take on this virus. The task is not only Titanic but is laced with intricate issues. Recently, an outbreak of fever with rash occurred on a tertiary care teaching hospital campus and was confirmed serologically as measles outbreak by IgMELISA. Therefore, we searched the literature related to outbreaks, transmission of the measles virus, age groups involved, vaccination strategies, vaccination failure and epidemiological features of the disease and reviewed the possible reasons for such outbreaks and problems in the global eradication of the virus.

  13. Glutathione Utilization by Candida albicans Requires a Functional Glutathione Degradation (DUG) Pathway and OPT7, an Unusual Member of the Oligopeptide Transporter Family

    Science.gov (United States)

    Desai, Prashant Ramesh; Thakur, Anil; Ganguli, Dwaipayan; Paul, Sanjoy; Morschhäuser, Joachim; Bachhawat, Anand K.

    2011-01-01

    Candida albicans lacks the ability to survive within its mammalian host in the absence of endogenous glutathione biosynthesis. To examine the ability of this yeast to utilize exogenous glutathione, we exploited the organic sulfur auxotrophy of C. albicans met15Δ strains. We observed that glutathione is utilized efficiently by the alternative pathway of glutathione degradation (DUG pathway). The major oligopeptide transporters OPT1–OPT5 of C. albicans that were most similar to the known yeast glutathione transporters were not found to contribute to glutathione transport to any significant extent. A genomic library approach to identify the glutathione transporter of C. albicans yielded OPT7 as the primary glutathione transporter. Biochemical studies on OPT7 using radiolabeled GSH uptake revealed a Km of 205 μm, indicating that it was a high affinity glutathione transporter. OPT7 is unusual in several aspects. It is the most remote member to known yeast glutathione transporters, lacks the two highly conserved cysteines in the family that are known to be crucial in trafficking, and also has the ability to take up tripeptides. The transporter was regulated by sulfur sources in the medium. OPT7 orthologues were prevalent among many pathogenic yeasts and fungi and formed a distinct cluster quite remote from the Saccharomyces cerevisiae HGT1 glutathione transporter cluster. In vivo experiments using a systemic model of candidiasis failed to detect expression of OPT7 in vivo, and strains disrupted either in the degradation (dug3Δ) or transport (opt7Δ) of glutathione failed to show a defect in virulence. PMID:21994941

  14. Inhibition of ERK1/2 Pathway Suppresses Adiponectin Secretion via Accelerating Protein Degradation by Ubiquitin-Proteasome System: Relevance to Obesity-related Adiponectin Decline

    Science.gov (United States)

    Gu, Dongfang; Wang, Zhigang; Dou, Xiaobing; Zhang, Ximei; Li, Songtao; Vu, Lyndsey; Yao, Tong; Song, Zhenyuan

    2013-01-01

    Objective Predominantly secreted by adipose tissue, adiponectin possesses insulin-sensitizing, anti-atherogenic, anti-inflammatory, and anti-angiogenic properties. Paradoxically, obesity is associated with declined plasma adiponectin levels; however, the underlying mechanisms remain elusive. In this study, we investigated the mechanistic involvement of MEK/ERK1/2 pathway in obesity-related adiponectin decrease. Materials/Methods C57 BL/6 mice exposed to a high-fat diet (HFD) were employed as animal obesity model. Both fully-differentiated 3T3-L1 and mouse primary adipocytes were used in the in vitro experiments. Results Obesity and plasma adiponectin decline induced by prolonged HFD exposure was associated with suppressed ERK1/2 activation in adipose tissue. In adipocytes, specific inhibition of MEK/ERK1/2 pathway decreased intracellular and secretory adiponectin levels, whereas adiponectin gene expression was increased, suggesting that MEK/ERK1/2 inhibition may promote adiponectin protein degradation. Cycloheximide (CHX)-chase assay revealed that MEK/ERK1/2 inhibition accelerated adiponectin protein degradation, which was prevented by MG132, a potent proteasome inhibitor. Immunoprecipitation assay showed that intracellular MEK/ERK1/2 activity was negatively associated with ubiqutinated adiponectin protein levels. Consistently, long-term HFD feeing in mice increased ubiquitinated adiponectin levels in the epididymal fat pads. Conclusions Adipose tissue MEK/ERK1/2 activity can differentially regulates adiponectin gene expression and protein abundance and its suppression in obesity may play a mechanistic role in obesity-related plasma adiponectin decline. PMID:23490586

  15. Degradation of di(2-ethyl hexyl) phthalate by Fusarium culmorum: Kinetics, enzymatic activities and biodegradation pathway based on quantum chemical modelingpathway based on quantum chemical modeling

    Energy Technology Data Exchange (ETDEWEB)

    Ahuactzin-Pérez, Miriam [Doctorado en Biología Experimental, Universidad Autónoma Metropolitana-Iztapalapa (UAM-I) (Mexico); Facultad de Agrobiología, Universidad Autónoma de Tlaxcala, Ixtacuixtla, Tlaxcala (Mexico); Tlecuitl-Beristain, Saúl; García-Dávila, Jorge [Universidad Politécnica de Tlaxcala, San Pedro Xalcatzinco, Tepeyanco, Tlaxcala CP 90180 (Mexico); González-Pérez, Manuel [Universidad Popular Autónoma del Estado de Puebla, Puebla CP 72410 (Mexico); Gutiérrez-Ruíz, María Concepción [Departamento de Ciencias de la Salud, Universidad Autónoma Metropolitana-Iztapalapa, D.F (Mexico); Sánchez, Carmen, E-mail: sanher6@hotmail.com [Laboratory of Biotechnology, Research Centre for Biological Sciences, Universidad Autónoma de Tlaxcala, Ixtacuixtla, Tlaxcala CP. 90062 (Mexico)

    2016-10-01

    Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer widely used in the manufacture of plastics, and it is an environmental contaminant. The specific growth rate (μ), maximum biomass (X{sub max}), biodegradation constant of DEHP (k), half-life (t{sub 1/2}) of DEHP biodegradation and removal efficiency of DEHP, esterase and laccase specific activities, and enzymatic yield parameters were evaluated for Fusarium culmorum grown on media containing glucose and different concentrations of DEHP (0, 500 and 1000 mg/L). The greatest μ and the largest X{sub max} occurred in media supplemented with 1000 mg of DEHP/L. F. culmorum degraded 95% of the highest amount of DEHP tested (1000 mg/L) within 60 h of growth. The k and t{sub 1/2} were 0.024 h{sup −1} and 28 h, respectively, for both DEHP concentrations. The removal efficiency of DEHP was 99.8% and 99.9% for 1000 and 500 mg/L, respectively. Much higher specific esterase activity than specific laccase activity was observed in all media tested. The compounds of biodegradation of DEHP were identified by GC–MS. A DEHP biodegradation pathway by F. culmorum was proposed on the basis of the intermolecular flow of electrons of the identified intermediate compounds using quantum chemical modeling. DEHP was fully metabolized by F. culmorum with butanediol as the final product. This fungus offers great potential in bioremediation of environments polluted with DEHP. - Highlights: • F. culmorum degraded 95% of DEHP (1000 mg/L) within 60 h. • Removal efficiency of DEHP was 99.8% and 99.9% for 1000 and 500 mg/L, respectively. • DEHP was fully metabolized by F. culmorum, with butanediol as the final product. • A DEHP biodegradation pathway was proposed using on quantum chemical modeling.

  16. Heterogeneous photo-Fenton decolorization of Orange II over Al-pillared Fe-smectite: Response surface approach, degradation pathway, and toxicity evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Li, Huiyuan; Li, Yanli [Department of Environmental Engineering, Wuhan University, Wuhan 430079 (China); Xiang, Luojing [Department of Environmental Engineering, Wuhan University, Wuhan 430079 (China); Université de Poitiers, UMR CNRS 7285, IC2MP, ENSIP, B1, 1 rue Marcel Doré, TSA 41105, Poitiers 86073 Cedex 9 (France); Huang, Qianqian; Qiu, Juanjuan [Department of Environmental Engineering, Wuhan University, Wuhan 430079 (China); Zhang, Hui, E-mail: eeng@whu.edu.cn [Department of Environmental Engineering, Wuhan University, Wuhan 430079 (China); Sivaiah, Matte Venkata; Baron, Fabien; Barrault, Joel; Petit, Sabine [Université de Poitiers, UMR CNRS 7285, IC2MP, ENSIP, B1, 1 rue Marcel Doré, TSA 41105, Poitiers 86073 Cedex 9 (France); Valange, Sabine, E-mail: sabine.valange@univ-poitiers.fr [Université de Poitiers, UMR CNRS 7285, IC2MP, ENSIP, B1, 1 rue Marcel Doré, TSA 41105, Poitiers 86073 Cedex 9 (France)

    2015-04-28

    Highlights: • Al-pillared Fe-smectite was synthesized and used as the photo-Fenton catalyst. • Response surface methodology was used to study the effects of reaction parameters. • The main intermediate products were identified by GC–MS technique. • A possible degradation pathway of Orange II was proposed. • All the generated products of Orange II were less toxic than the original dye. - Abstract: A ferric smectite clay material was synthesized and further intercalated with Al{sub 2}O{sub 3} pillars for the first time with the aim of evaluating its ability to be used as heterogeneous catalyst for the photo-Fenton decolorization of azo dye Orange II. UV irradiation was found to enhance the activity of the catalyst in the heterogeneous photo-Fenton process. Catalyst loading of 0.5 g/L and hydrogen peroxide concentration of 13.5 mM yielded a remarkable color removal, accompanied by excellent catalyst stability. The decolorization of Orange II followed the pseudo-first-order kinetics for initial dye concentrations from 20 to 160 mg/L. The central composite design (CCD) based on the response surface methodology (RSM) was applied to evaluate the effects of several operating parameters, namely initial pH, catalyst loading and hydrogen peroxide concentration, on the decolorization efficiency. The RSM model was derived and the response surface plots were developed based on the results. Moreover, the main intermediate products were separated and identified using gas chromatography–mass spectrometry (GC–MS) and a possible degradation pathway was proposed accordingly. The acute toxicity experiments illustrated that the Daphniamagna immobilization rate continuously decreased during 150 min reaction, indicating that the effluent was suitable for sequential biological treatment.

  17. Decolorization of azo dye C.I. Reactive Black 5 by ozonation in aqueous solution: influencing factors, degradation products, reaction pathway and toxicity assessment.

    Science.gov (United States)

    Zheng, Qing; Dai, Yong; Han, Xiangyun

    2016-01-01

    In this study, ozonation treatment of C.I. Reactive Black 5 (RB5) was investigated at various operating parameters. The results showed that the aqueous solution initially containing 200 mg/L RB5 was quickly decolorized at pH 8.0 with an ozone dose of 3.2 g/h. Reaction intermediates with m/z 281, 546, 201, 350, 286 and 222 were elucidated using liquid chromatography-mass spectrometry, while sulfate ion, nitrate ion and three carboxylic acids (i.e., oxalic acid, formic acid, and acetic acid) were identified by ion exchange chromatography. Thus, the cleavage of the azo bond and the introduction of OH groups in the corresponding positions were proposed as the predominant reaction pathway. The detachment of sulfonic groups was also commonly observed during the ozonation treatment. The proposed degradation mechanism was confirmed by frontier electron density calculations, suggesting the feasibility of predicting the major events in the whole ozonation process with the computational method. Compared with RB5 degradation, the reduction of total organic carbon (TOC) proceeded much more slowly, and approximately 54% TOC was removed after 4 h of ozonation. Acute toxicity tests with Photobacterium phosphoreum showed that the toxicity of reaction solution was firstly increased and then decreased to a negligible level after 160 min.

  18. Kinetic analysis and degradation pathway for m-dichlorobenzene removal by Brevibacillus agri DH-1 and its performance in a biotrickling filter.

    Science.gov (United States)

    Yang, Bai-Ren; Sun, Zhu-Qiu; Wang, Li-Ping; Li, Zhao-Xia; Ding, Cheng

    2017-05-01

    A strain, Brevibacillus agri DH-1, isolated from dry lands was used to remove m-dichlorobenzene. After 48h culturing, the concentrations of m-dichlorobenzene decreased from 26-130 to 7.87-28.87mg/L and dry cell weight for bacterial growth reached 52.43-75.05mg/L. The growth and degradation kinetics were analyzed by the fitting of Haldane-Andrews model and pseudo first-order model. A degradation pathway was proposed according to major intermediates (phenol), chloride ion variation, ring-opening enzyme activity, and high mineralization (0.47gCl-/gm-dichlorobenzene, 0.65 gco2/gm-dichlorobenzene, 0.15 gDCW/gm-dichlorobenzene). In addition, the performance in a biotrickling filter (BTF) was evaluated through removal efficiency and pressure drop values with increasing inlet loading rate from 4.10 to 122.57g/m(3)/h at three empty bed residence time points (30s, 60s, and 90s). The results demonstrated that strain DH-1 possessed high removal efficiency and stable operation in a BTF.

  19. Correlation between degradation pathway and toxicity of acetaminophen and its by-products by using the electro-Fenton process in aqueous media.

    Science.gov (United States)

    Le, Thi Xuan Huong; Nguyen, Thi Van; Amadou Yacouba, Zoulkifli; Zoungrana, Laetitia; Avril, Florent; Nguyen, Duy Linh; Petit, Eddy; Mendret, Julie; Bonniol, Valerie; Bechelany, Mikhael; Lacour, Stella; Lesage, Geoffroy; Cretin, Marc

    2017-04-01

    The evolution of the degradation by-products of an acetaminophen (ACE) solution was monitored by HPLC-UV/MS and IC in parallel with its ecotoxicity (Vibrio fischeri 81.9%, Microtox(®) screening tests) during electro-Fenton (EF) oxidation performed on carbon felt. The aromatic compounds 2-hydroxy-4-(N-acetyl) aminophenol, 1,4-benzoquinone, benzaldehyde and benzoic acid were identified as toxic sub-products during the first stage of the electrochemical treatment, whereas aliphatic short-chain carboxylic acids (oxalic, maleic, oxamic, formic, acetic and fumaric acids) and inorganic ions (ammonium and nitrate) were well identified as non-toxic terminal sub-products. Electrogenerated hydroxyl radicals then converted the eco-toxic and bio-refractory property of initial ACE molecule (500 mL, 1 mM) and subsequent aromatic sub-products into non-toxic compounds after 2 h of EF treatment. The toxicity of every intermediate produced during the mineralization of ACE was quantified, and a relationship was established between the degradation pathway of ACE and the global toxicity evolution of the solution. After 8 h of treatment, a total organic carbon removal of 86.9% could be reached for 0.1 mM ACE at applied current of 500 mA with 0.2 mM of Fe(2+) used as catalyst. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Electroacupuncture inhibits apoptosis in annulus fibrosis cells through suppression of the mitochondria-dependent pathway in a rat model of cervical intervertebral disc degradation

    Directory of Open Access Journals (Sweden)

    Jun Liao

    2012-01-01

    Full Text Available The purpose of this study was to investigate whether treatment with electroacupuncture (EA inhibited mitochondria-dependent apoptosis in annulus fibrosis (AF cells in a rat model of cervical intervertebral disc degradation induced by unbalanced dynamic and static forces. Forty Sprague-Dawley rats were used in this study, of which 30 underwent surgery to induce cervical intervertebral disc degradation, 10 rats received EA at acupoints Dazhui (DU 14 and Shousanli (LI 10. TUNEL staining was measured to assess apoptosis in AF cells, immunohistochemistry was used to examine Bcl-2 and Bax expression, colorimetric assays were used to determine caspase 9 and caspase 3 activities and RT-PCR and western blotting were used to assess the mRNA and protein expression of Crk and ERK2. Treatment with EA reduced the number of AF-positive cells in TUNEL staining, increased Bcl-2-positive cells and decreased Bax-positive cells in immunohistochemical staining, significantly inhibited the activation of caspases-9 and -3, and enhanced the mRNA and protein expression of Crk and ERK2. Our data show that EA inhibits AF cell apoptosis via the mitochondria-dependent pathway and up-regulates Crk and ERK2 expression. These results suggest that treatment with may be a good alternative therapy for preventing cervical spondylosis.

  1. Mice deficient for ERAD machinery component Sel1L develop central diabetes insipidus.

    Science.gov (United States)

    Bichet, Daniel G; Lussier, Yoann

    2017-10-02

    Deficiency of the antidiuretic hormone arginine vasopressin (AVP) underlies diabetes insipidus, which is characterized by the excretion of abnormally large volumes of dilute urine and persistent thirst. In this issue of the JCI, Shi et al. report that Sel1L-Hrd1 ER-associated degradation (ERAD) is responsible for the clearance of misfolded pro-arginine vasopressin (proAVP) in the ER. Additionally, mice with Sel1L deficiency, either globally or specifically within AVP-expressing neurons, developed central diabetes insipidus. The results of this study demonstrate a role for ERAD in neuroendocrine cells and serve as a clinical example of the effect of misfolded ER proteins retrotranslocated through the membrane into the cytosol, where they are polyubiquitinated, extracted from the ER membrane, and degraded by the proteasome. Moreover, proAVP misfolding in hereditary central diabetes insipidus likely shares common physiopathological mechanisms with proinsulin misfolding in hereditary diabetes mellitus of youth.

  2. Stimulatory effects of the degradation products from Mg-Ca-Sr alloy on the osteogenesis through regulating ERK signaling pathway

    Science.gov (United States)

    Li, Mei; He, Peng; Wu, Yuanhao; Zhang, Yu; Xia, Hong; Zheng, Yufeng; Han, Yong

    2016-09-01

    The influence of Mg-1Ca-xwt.% Sr (x = 0.2, 0.5, 1.0, 2.0) alloys on the osteogenic differentiation and mineralization of pre-osteoblast MC3T3-E1 were studied through typical differentiation markers, such as intracellular alkaline phosphatase (ALP) activity, extracellular collagen secretion and calcium nodule formation. It was shown that Mg-1Ca alloys with different content of Sr promoted cell viability and enhanced the differentiation and mineralization levels of osteoblasts, and Mg-1Ca-2.0Sr alloy had the most remarkable and significant effect among all. To further investigate the underlying mechanisms, RT-PCR and Western Blotting assays were taken to analyze the mRNA expression level of osteogenesis-related genes and intracellular signaling pathways involved in osteogenesis, respectively. RT-PCR results showed that Mg-1Ca-2.0Sr alloy significantly up-regulated the expressions of the transcription factors of Runt-related transcription factor 2 (RUNX2) and Osterix (OSX), Integrin subunits, as well as alkaline phosphatase (ALP), Bone sialoprotein (BSP), Collagen I (COL I), Osteocalcin (OCN) and Osteopontin (OPN). Western Blotting results suggested that Mg-1Ca-2.0Sr alloy rapidly induced extracellular signal-regulated kinase (ERK) activation but showed no obvious effects on c-Jun N terminal kinase (JNK) and p38 kinase of MAPK. Taken together, our results demonstrated that Mg-1Ca-2.0Sr alloy had excellent biocompatibility and osteogenesis via the ERK pathway and is expected to be promising as orthopedic implants and bone repair materials.

  3. Decomposition of acetaminophen in water by a gas phase dielectric barrier discharge plasma combined with TiO2-rGO nanocomposite: Mechanism and degradation pathway

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Guyu; Sun, Yabing, E-mail: sybnju@163.com; Zhang, Chunxiao; Yu, Zhongqing

    2017-02-05

    Highlights: • Graphene Oxide-based catalyst was first applied with dielectric barrier discharge plasma. • The TiO{sub 2}-rGO showed efficient synergistic effect with gas phase dielectric barrier discharge plasma. • The property changes of TiO{sub 2}-rGO nanocomposite after plasma treatment were characterized. • The mechanism and possible pathways of APAP degradation in plasma/TiO{sub 2}-rGO system were proposed. - Abstract: Acetaminophen (APAP) served as the model pollutant to evaluate the feasibility of pollutant removal by gas phase dielectric barrier discharge plasma combined with the titanium dioxide-reduced Graphene Oxide (TiO{sub 2}-rGO) nanocomposite. TiO{sub 2}-rGO nanocomposite was prepared using the modified hydrothermal method and characterized by TEM and XPS before and after plasma process. The results indicated that the APAP degradation efficiency was significantly improved to 92% after 18 min of discharge plasma treatment coupling 0.25 g L{sup −1} TiO{sub 2}-rGO 5% wt at 18 kV, compared with the plasma alone and plasma combined with P25 TiO{sub 2}. The degradation mechanism for APAP in this system was studied by investigating the effects of the operational variables (e.g. discharge voltage and pH value) and the amount of the generated active species; and the results showed that O{sub 3} and H{sub 2}O{sub 2} yields were influenced notably by adding TiO{sub 2}-rGO. Also, it was observed that, compared with unused TiO{sub 2}-rGO, the photocatalytic performance of used TiO{sub 2}-rGO declined after several recirculation times due to the further reduction of Graphene Oxide in plasma system. Finally, intermediate products were analyzed by UV–vis spectrometry and HPLC/MS, and possible transformation pathways were identified with the support of theoretically calculating the frontier electron density of APAP.

  4. A research agenda for malaria eradication: vaccines.

    NARCIS (Netherlands)

    Abdulla, S.; Agre, P.; Alonso, P.L.; Arevalo-Herrera, M.; Bassat, Q.; Binka, F.; Chitnis, C.; Corradin, G.; Cowman, A. F.; Culpepper, J.; Portillo, H. del; Dinglasan, R.R.; Duffy, P.; Gargallo, D.; Greenwood, B.; Guinovart, C.; Hall, B.F.; Herrera, S.; Hoffman, S.; Lanzavecchia, A.; Leroy, O.; Levine, M.M.; Loucq, C.; Mendis, K.; Milman, J.; Moorthy, V.S.; Pleuschke, G.; Plowe, C.V.; Reed, S.; Sauerwein, R.W.; Saul, A.; Schofield, L.; Sinden, R.R.; Stubbs, J.; Villafana, T.; Wirth, D.; Yadav, P.; Ballou, R.; Brown, G.; Birkett, A.; Brandt, W.; Brooks, A.; Carter, T.; Golden, A.; Lee, C.; Nunes, J.; Puijalon, O.; Raphael, T.; Richards, H.; Warren, C.; Woods, C.

    2011-01-01

    Vaccines could be a crucial component of efforts to eradicate malaria. Current attempts to develop malaria vaccines are primarily focused on Plasmodium falciparum and are directed towards reducing morbidity and mortality. Continued support for these efforts is essential, but if mal

  5. Brazil : Eradicating Child Labor in Brazil

    OpenAIRE

    World Bank

    2001-01-01

    The report reviews evidence of child labor in Brazil, and the Government's efforts to eradicate its worst forms, by examining background assessments of ongoing programs for its prevention. It seeks to identify promising strategies, addressing the needs of highly vulnerable children in urban areas, engaged in activities such as drug commerce, prostitution, or other dangerous activities. One...

  6. Small-Molecule NSC59984 Restores p53 Pathway Signaling and Antitumor Effects against Colorectal Cancer via p73 Activation and Degradation of Mutant p53.

    Science.gov (United States)

    Zhang, Shengliang; Zhou, Lanlan; Hong, Bo; van den Heuvel, A Pieter J; Prabhu, Varun V; Warfel, Noel A; Kline, Christina Leah B; Dicker, David T; Kopelovich, Levy; El-Deiry, Wafik S

    2015-09-15

    The tumor-suppressor p53 prevents cancer development via initiating cell-cycle arrest, cell death, repair, or antiangiogenesis processes. Over 50% of human cancers harbor cancer-causing mutant p53. p53 mutations not only abrogate its tumor-suppressor function, but also endow mutant p53 with a gain of function (GOF), creating a proto-oncogene that contributes to tumorigenesis, tumor progression, and chemo- or radiotherapy resistance. Thus, targeting mutant p53 to restore a wild-type p53 signaling pathway provides an attractive strategy for cancer therapy. We demonstrate that small-molecule NSC59984 not only restores wild-type p53 signaling, but also depletes mutant p53 GOF. NSC59984 induces mutant p53 protein degradation via MDM2 and the ubiquitin-proteasome pathway. NSC59984 restores wild-type p53 signaling via p73 activation, specifically in mutant p53-expressing colorectal cancer cells. At therapeutic doses, NSC59984 induces p73-dependent cell death in cancer cells with minimal genotoxicity and without evident toxicity toward normal cells. NSC59984 synergizes with CPT11 to induce cell death in mutant p53-expressing colorectal cancer cells and inhibits mutant p53-associated colon tumor xenograft growth in a p73-dependent manner in vivo. We hypothesize that specific targeting of mutant p53 may be essential for anticancer strategies that involve the stimulation of p73 in order to efficiently restore tumor suppression. Taken together, our data identify NSC59984 as a promising lead compound for anticancer therapy that acts by targeting GOF-mutant p53 and stimulates p73 to restore the p53 pathway signaling.

  7. Copper-promoted circumneutral activation of H2O2 by magnetic CuFe2O4 spinel nanoparticles: Mechanism, stoichiometric efficiency, and pathway of degrading sulfanilamide.

    Science.gov (United States)

    Feng, Yong; Liao, Changzhong; Shih, Kaimin

    2016-07-01

    To evaluate the heterogeneous degradation of sulfanilamide by external energy-free Fenton-like reactions, magnetic CuFe2O4 spinel nanoparticles (NPs) were synthesized and used as catalysts for activation of hydrogen peroxide (H2O2). The physicochemical properties of the CuFe2O4 NPs were characterized with several techniques, including X-ray diffraction, X-ray photoelectron spectroscopy, transmission electron microscopy, and magnetometry. In the catalytic experiments, CuFe2O4 NPs/H2O2 oxidation showed the best degradation performance in the circumneutral conditions that resulted from the presence of Cu(II) on the surface of the CuFe2O4 NPs. The surface area-normalized pseudo-first-order rate constants were calculated as 2.60 × 10(-2) L m(-1) min(-1), 2.58 × 10(-3) L m(-1) min(-1), 1.92 × 10(-3) L m(-1) min(-1), and 7.30 × 10(-4) L m(-1) min(-1) for CuO, CuFe2O4 NPs, Fe3O4, and α-Fe2O3 catalysts, respectively. Thus, solid state Cu(II) was more reactive and efficient than Fe(III) in the circumneutral activation of H2O2; this finding was further supported by the results regarding the stoichiometric efficiency of H2O2. The effects of experimental parameters such as the oxidant dosage and catalyst loading were investigated. The mechanism for H2O2 activation on the spinel surface was explored and could be explained by the solid redox cycles of Fe(II)/Fe(III) and Cu(II)/Cu(I). Based on the products detected, a degradation pathway via the CS bond cleavage is proposed for the degradation of sulfanilamide. The findings of this study suggest that copper can be used as a doping metal to improve the reactivity and expand the effective pH range of iron oxides. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Electro-Fenton oxidation of para-aminosalicylic acid: degradation kinetics and mineralization pathway using Pt/carbon-felt and BDD/carbon-felt cells.

    Science.gov (United States)

    Oturan, Nihal; Aravindakumar, Charuvila T; Olvera-Vargas, Hugo; Sunil Paul, Mathew M; Oturan, Mehmet A

    2017-05-31

    Degradation of a widely used antibiotic, the para-aminosalicylic acid (PAS), and mineralization of its aqueous solution was investigated by electro-Fenton process using Pt/carbon-felt and boron-doped diamond (BDD)/carbon-felt cells with applied currents in the range of 50-1000 mA. This process produces the highly oxidizing species, the hydroxyl radical ((•)OH), which is mainly responsible for the oxidative degradation of PAS. An absolute rate constant of 4.17 × 10(9) M(-1) s(-1) for the oxidation of PAS by (●)OH was determined from the competition kinetics method. Degradation rate of PAS increased with current reaching an optimal value of 500 mA with complete disappearance of 0.1 mM PAS at 7 min using Pt/carbon-felt cell. The optimum degradation rate was reached at 300 mA for BDD/carbon-felt. The latter cell was found more efficient in total organic carbon (TOC) removal where a complete mineralization was achieved within 240 min. A multi-step mineralization process was observed with the formation of a number of aromatic intermediates, short-chain carboxylic acids, and inorganic ions. Eight aromatic intermediate products were identified using both LC-Q-ToF-MS and GC-MS techniques. These products were the result of hydroxylation of PAS followed by multiple additions of hydroxyl radicals to form polyhydroxylated derivatives. HPLC and GC/MS analyses demonstrated that extended oxidation of these intermediate products conducted to the formation of various short-chain carboxylic acids. Prolonged electrolysis resulted in a complete mineralization of PAS with the evolution of inorganic ions such as NO3(-) and NH4(+). Based on the identified intermediates, carboxylic acids and inorganic ions, a plausible mineralization pathway is also deduced. The remarkably high degree of mineralization (100%) achieved by the present EF process highlights the potential application of this technique to the complete removal of salicylic acid-based pharmaceuticals from

  9. Transport and degradation of dissolved organic matter and associated freshwater pathways in the Laptev Sea (Siberian Arctic)

    Science.gov (United States)

    Hoelemann, Jens; Janout, Markus; Koch, Boris; Bauch, Dorothea; Hellmann, Sebastian; Eulenburg, Antje; Heim, Birgit; Kassens, Heidemarie; Timokhov, leonid

    2016-04-01

    The Siberian shelves are seasonally ice-covered and characterized by large freshwater runoff rates from some of the largest rivers on earth. These rivers also provide a considerable amount of dissolved organic carbon (DOC) to the Arctic Ocean. With an annual load of about 6 Tg DOC a-1 the Lena River contributes nearly 20 percent of the annual DOC discharge to the Arctic Ocean. We present a comprehensive dataset collected during multiple Laptev Sea expeditions carried out in spring, summer and fall (2010-15) in order to explore the processes controlling the dispersal and degradation of DOM during the river water's passage across the shelf. Our investigations are focused on CDOM (Colored Dissolved Organic Matter), which resembles the DOC concentration, interacts with solar radiation and forms a major fraction of the organic matter pool. Our results show an inverse correlation between salinity and CDOM, which emphasizes its terrigenous source. Further, the spectral slope of CDOM absorption indicates that photochemical bleaching is the main process that reduces the CDOM absorption (~ 20%) in freshwater along its transport across the shelf. The distribution of the Lena river water is primarily controlled by winds in summer. During summers with easterly or southerly winds, the plume remains on the central and northern Laptev shelf, and is available for export into the Arctic Basin. The CDOM-rich river water increases the absorption of solar radiation and enhances warming of a shallow surface layer. This emphasizes the importance of CDOM for sea surface temperatures and lateral ice melt on the shelf and adjacent basin. DOC concentrations in freshwater vary seasonally and become larger with increasing discharge. Our data indicate that the CDOM concentrations are highest during the freshet when landfast ice is still present. Subsequent mixing with local sea ice meltwater lowers CDOM to values that are characteristic for the Lena freshwater during the rest of the year.

  10. Loquat (Eriobotrya japonica) extract prevents dexamethasone-induced muscle atrophy by inhibiting the muscle degradation pathway in Sprague Dawley rats.

    Science.gov (United States)

    Noh, Kyung Kyun; Chung, Ki Wung; Sung, Bokyung; Kim, Min Jo; Park, Chan Hum; Yoon, Changshin; Choi, Jae Sue; Kim, Mi Kyung; Kim, Cheol Min; Kim, Nam Deuk; Chung, Hae Young

    2015-09-01

    In the Orient, loquat (Eriobotrya japonica) extract (LE) is widely used in teas, food and folk medicines. The leaves of the loquat tree have been used for generations to treat chronic bronchitis, coughs, phlegm production, high fever and gastroenteric disorders. One of the major active components of loquat leaves is ursolic acid, which was recently investigated in the context of preventing muscle atrophy. The present study investigated the therapeutic potential of LE on dexamethasone‑induced muscle atrophy in rats. Daily intraperitoneal injections of dexamethasone caused muscle atrophy and evidence of muscle atrophy prevention by LE was demonstrated using various assays. In particular, dexamethasone‑induced grip strength loss was alleviated by LE and the increase in serum creatine kinase activity, a surrogate marker of muscle damage, caused by dexamethasone injection was reduced by LE. Western blot analysis and immunoprecipitation demonstrated that dexamethasone markedly increased the protein expression levels of muscle ring finger 1 (MuRF1), which causes the ubiquitination and degradation of myosin heavy chain (MyHC), and decreased the protein expression levels of MyHC as well as increased the ubiquitinated MyHC to MyHC ratio. However, LE reduced the dexamethasone‑induced protein expression levels of MuRF1 and ubiquitinated MyHC. Additional experiments revealed that LE supplementation inhibited the nuclear translocation of FoxO1 induced by dexamethasone. These findings suggested that LE prevented dexamethasone‑induced muscle atrophy by regulating the FoxO1 transcription factor and subsequently the expression of MuRF1.

  11. Can leprosy be eradicated with chemotherapy? An evaluation of the Malta Leprosy Eradication Project.

    Science.gov (United States)

    Jacobson, Robert R; Gatt, Paul

    2008-12-01

    The Malta Leprosy Eradication Project (MLEP) was proposed in 1971 by Freerksen with the aim of eradicating leprosy in Malta. The project involved re-treatment of all known cases in Malta as of 1972 and all new cases thereafter with a regimen consisting of Isoprodian (a combination of dapsone, prothionamide and isoniazid) and rifampicin for varying intervals depending on the severity of their disease and their response to treatment. Overall the response to therapy was excellent with an extremely low relapse rate. During the 30 years of the project the incidence of leprosy steadily decreased continuing a decline that had started at least two decades earlier and Freerksen declared the disease eradicated from Malta in 2001. Although given the long incubation period of leprosy cases may still be occasionally detected in the future, the disease has been basically eradicated at this time and there are no patients currently receiving treatment. This work was done at the leprosy clinic, Boffa Hospital, Floriana, Malta.

  12. Mannosidase IA is in Quality Control Vesicles and Participates in Glycoprotein Targeting to ERAD.

    Science.gov (United States)

    Ogen-Shtern, Navit; Avezov, Edward; Shenkman, Marina; Benyair, Ron; Lederkremer, Gerardo Z

    2016-08-14

    Endoplasmic reticulum-associated degradation (ERAD) of a misfolded glycoprotein in mammalian cells requires the removal of 3-4 alpha 1,2 linked mannose residues from its N-glycans. The trimming and recognition processes are ascribed to ER Mannosidase I, the ER-degradation enhancing mannosidase-like proteins (EDEMs), and the lectins OS-9 and XTP3-B, all residing in the ER, the ER-derived quality control compartment (ERQC), or quality control vesicles (QCVs). Folded glycoproteins with untrimmed glycans are transported from the ER to the Golgi complex, where they are substrates of other alpha 1,2 mannosidases, IA, IB, and IC. The apparent redundancy of these enzymes has been puzzling for many years. We have now determined that, surprisingly, mannosidase IA is not located in the Golgi but resides in QCVs. We had recently described this type of vesicles, which carry ER α1,2 mannosidase I (ERManI). We show that the overexpression of alpha class I α1,2 mannosidase IA (ManIA) significantly enhances the degradation of ERAD substrates and its knockdown stabilizes it. Our results indicate that ManIA trims mannose residues from Man9GlcNAc2 down to Man5GlcNAc2, acting in parallel with ERManI and the EDEMs, and targeting misfolded glycoproteins to ERAD.

  13. Reflux esophagitis triggered after Helicobacter pylori eradication: a noteworthy demerit of eradication therapy among the Japanese?

    Directory of Open Access Journals (Sweden)

    Katsunori eIijima

    2015-06-01

    Full Text Available In the February 2013 Revision of Insured Medical Treatment, bacterial eradication for all Helicobacter pylori-positive individuals in Japan was covered under the insurance scheme. However, reflux esophagitis is believed to occur in approximately 10% of Japanese patients who undergo eradication therapy. Hence, the risk of reflux esophagitis among such cases should be carefully considered, particularly in the treatment for H. pylori-positive patients who are otherwise healthy. The eradication of Helicobacter pylori in cases of H. pylori-positive gastritis markedly suppresses gastric inflammation, and inhibits gastric mucosal atrophy and its progression to intestinal metaplasia. In a long-term follow-up study (10-20 years, eradication treatment was found to reduce the risk of subsequent gastric cancer. However, the fact that eradication-induced reflux esophagitis could increase the long-term risk of Barrett’s esophagus and esophageal adenocarcinoma should also be considered in the Japanese population. Appropriate treatment with proton pump inhibitors should be taken into consideration for patients undergoing eradication therapy in clinical practice.

  14. Aadh2p: an Arxula adeninivorans alcohol dehydrogenase involved in the first step of the 1-butanol degradation pathway.

    Science.gov (United States)

    Rauter, Marion; Kasprzak, Jakub; Becker, Karin; Riechen, Jan; Worch, Sebastian; Hartmann, Anja; Mascher, Martin; Scholz, Uwe; Baronian, Kim; Bode, Rüdiger; Schauer, Frieder; Matthias Vorbrodt, H; Kunze, Gotthard

    2016-10-12

    The non-conventional yeast Arxula adeninivorans uses 1-butanol as a carbon source and has recently attracted attention as a promising organism for 1-butanol production. Alcohol dehydrogenases (adhp) are important catalysts in 1-butanol metabolism, but only Aadh1p from Arxula has been characterized. This enzyme is involved in ethanol synthesis but has a low impact on 1-butanol degradation. In this study, we identified and characterized a second adhp from A. adeninivorans (Aadh2p). Compared to Saccharomyces cerevisiae ADHs' (ScAdh) protein sequences it originates from the same ancestral node as ScAdh6p, 7p and 4p. It is also localized in the cytoplasm and uses NAD(H) as cofactor. The enzyme has its highest activity with medium chain-length alcohols and maximum activity with 1-butanol with the catalytic efficiency of the purified enzyme being 42 and 43,000 times higher than with ethanol and acetaldehyde, respectively. Arxula adeninivorans strain G1212/YRC102-AADH2, which expresses the AADH2 gene under the control of the strong constitutive TEF1 promoter was constructed. It achieved an ADH activity of up to 8000 U/L and 500 U/g dry cell weight (dcw) which is in contrast to the control strain G1212/YRC102 which had an ADH activity of up to 1400 U/L and 200 U/g dcw. Gene expression analysis showed that AADH2 derepression or induction using non-fermentable carbon-sources such as ethanol, pyruvate, glycerol or 1-butanol did occur. Compared to G1212/YRC102 AADH2 knock-out strain had a slower growth rate and lower 1-butanol consumption if 1-butanol was used as sole carbon source and AADH2-transformants did not grow at all in the same conditions. However, addition of the branched-chain amino acids leucine, isoleucine and valine allowed the transformants to use 1-butanol as carbon source. The addition of these amino acids to the control strain and Δaadh2 mutant cultures had the effect of accelerating 1-butanol consumption. Our results confirm that Aadh2p plays a major

  15. Hepatic cytochromes P450: structural degrons and barcodes, posttranslational modifications and cellular adapters in the ERAD-endgame.

    Science.gov (United States)

    Kim, Sung-Mi; Wang, YongQiang; Nabavi, Noushin; Liu, Yi; Correia, Maria Almira

    2016-08-01

    The endoplasmic reticulum (ER)-anchored hepatic cytochromes P450 (P450s) are enzymes that metabolize endo- and xenobiotics i.e. drugs, carcinogens, toxins, natural and chemical products. These agents modulate liver P450 content through increased synthesis or reduction via inactivation and/or proteolytic degradation, resulting in clinically significant drug-drug interactions. P450 proteolytic degradation occurs via ER-associated degradation (ERAD) involving either of two distinct routes: Ubiquitin (Ub)-dependent 26S proteasomal degradation (ERAD/UPD) or autophagic lysosomal degradation (ERAD/ALD). CYP3A4, the major human liver/intestinal P450, and the fast-turnover CYP2E1 species are degraded via ERAD/UPD entailing multisite protein phosphorylation and subsequent ubiquitination by gp78 and CHIP E3 Ub-ligases. We are gaining insight into the nature of the structural determinants involved in CYP3A4 and CYP2E1 molecular recognition in ERAD/UPD [i.e. K48-linked polyUb chains and linear and/or "conformational" phosphodegrons consisting either of consecutive sequences on surface loops and/or disordered regions, or structurally-assembled surface clusters of negatively charged acidic (Asp/Glu) and phosphorylated (Ser/Thr) residues, within or vicinal to which, Lys-residues are targeted for ubiquitination]. Structural inspection of select human liver P450s reveals that such linear or conformational phosphodegrons may indeed be a common P450-ERAD/UPD feature. By contrast, although many P450s such as the slow-turnover CYP2E1 species and rat liver CYP2B1 and CYP2C11 are degraded via ERAD/ALD, little is known about the mechanism of their ALD-targeting. On the basis of our current knowledge of ALD-substrate targeting, we propose a tripartite conjunction of K63-linked Ub-chains, P450 structural "LIR" motifs and selective cellular "cargo receptors" as plausible P450-ALD determinants.

  16. Tay-Sachs disease mutations in HEXA target the α chain of hexosaminidase A to endoplasmic reticulum-associated degradation.

    Science.gov (United States)

    Dersh, Devin; Iwamoto, Yuichiro; Argon, Yair

    2016-12-01

    Loss of function of the enzyme β-hexosaminidase A (HexA) causes the lysosomal storage disorder Tay-Sachs disease (TSD). It has been proposed that mutations in the α chain of HexA can impair folding, enzyme assembly, and/or trafficking, yet there is surprisingly little known about the mechanisms of these potential routes of pathogenesis. We therefore investigated the biosynthesis and trafficking of TSD-associated HexA α mutants, seeking to identify relevant cellular quality control mechanisms. The α mutants E482K and G269S are defective in enzymatic activity, unprocessed by lysosomal proteases, and exhibit altered folding pathways compared with wild-type α. E482K is more severely misfolded than G269S, as observed by its aggregation and inability to associate with the HexA β chain. Importantly, both mutants are retrotranslocated from the endoplasmic reticulum (ER) to the cytosol and are degraded by the proteasome, indicating that they are cleared via ER-associated degradation (ERAD). Leveraging these discoveries, we observed that manipulating the cellular folding environment or ERAD pathways can alter the kinetics of mutant α degradation. Additionally, growth of patient fibroblasts at a permissive temperature or with chemical chaperones increases cellular Hex activity by improving mutant α folding. Therefore modulation of the ER quality control systems may be a potential therapeutic route for improving some forms of TSD.

  17. Tay–Sachs disease mutations in HEXA target the α chain of hexosaminidase A to endoplasmic reticulum–associated degradation

    Science.gov (United States)

    Dersh, Devin; Iwamoto, Yuichiro; Argon, Yair

    2016-01-01

    Loss of function of the enzyme β-hexosaminidase A (HexA) causes the lysosomal storage disorder Tay–Sachs disease (TSD). It has been proposed that mutations in the α chain of HexA can impair folding, enzyme assembly, and/or trafficking, yet there is surprisingly little known about the mechanisms of these potential routes of pathogenesis. We therefore investigated the biosynthesis and trafficking of TSD-associated HexA α mutants, seeking to identify relevant cellular quality control mechanisms. The α mutants E482K and G269S are defective in enzymatic activity, unprocessed by lysosomal proteases, and exhibit altered folding pathways compared with wild-type α. E482K is more severely misfolded than G269S, as observed by its aggregation and inability to associate with the HexA β chain. Importantly, both mutants are retrotranslocated from the endoplasmic reticulum (ER) to the cytosol and are degraded by the proteasome, indicating that they are cleared via ER-associated degradation (ERAD). Leveraging these discoveries, we observed that manipulating the cellular folding environment or ERAD pathways can alter the kinetics of mutant α degradation. Additionally, growth of patient fibroblasts at a permissive temperature or with chemical chaperones increases cellular Hex activity by improving mutant α folding. Therefore modulation of the ER quality control systems may be a potential therapeutic route for improving some forms of TSD. PMID:27682588

  18. Gamma-Glutamylpolyamine Synthetase GlnA3 Is Involved in the First Step of Polyamine Degradation Pathway in Streptomyces coelicolor M145

    Directory of Open Access Journals (Sweden)

    Agnieszka Bera

    2017-04-01

    Full Text Available Streptomyces coelicolor M145 was shown to be able to grow in the presence of high concentrations of polyamines, such as putrescine, cadaverine, spermidine, or spermine, as a sole nitrogen source. However, hardly anything is known about polyamine utilization and its regulation in streptomycetes. In this study, we demonstrated that only one of the three proteins annotated as glutamine synthetase-like protein, GlnA3 (SCO6962, was involved in the catabolism of polyamines. Transcriptional analysis revealed that the expression of glnA3 was strongly induced by exogenous polyamines and repressed in the presence of ammonium. The ΔglnA3 mutant was shown to be unable to grow on defined Evans agar supplemented with putrescine, cadaverine, spermidine, and spermine as sole nitrogen source. HPLC analysis demonstrated that the ΔglnA3 mutant accumulated polyamines intracellularly, but was unable to degrade them. In a rich complex medium supplemented with a mixture of the four different polyamines, the ΔglnA3 mutant grew poorly showing abnormal mycelium morphology and decreased life span in comparison to the parental strain. These observations indicated that the accumulation of polyamines was toxic for the cell. An in silico analysis of the GlnA3 protein model suggested that it might act as a gamma-glutamylpolyamine synthetase catalyzing the first step of polyamine degradation. GlnA3-catalyzed glutamylation of putrescine was confirmed in an enzymatic in vitro assay and the GlnA3 reaction product, gamma-glutamylputrescine, was detected by HPLC/ESI-MS. In this work, the first step of polyamine utilization in S. coelicolor has been elucidated and the putative polyamine utilization pathway has been deduced based on the sequence similarity and transcriptional analysis of homologous genes expressed in the presence of polyamines.

  19. Sel1L is indispensable for mammalian endoplasmic reticulum-associated degradation, endoplasmic reticulum homeostasis, and survival

    NARCIS (Netherlands)

    Sun, S.; Shi, Guojun; Han, X.; Francisco, A.; Ji, Y.; Kersten, A.H.

    2014-01-01

    Suppressor/Enhancer of Lin-12-like (Sel1L) is an adaptor protein for the E3 ligase hydroxymethylglutaryl reductase degradation protein 1 (Hrd1) involved in endoplasmic reticulum-associated degradation (ERAD). Sel1L’s physiological importance in mammalian ERAD, however, remains to be established. Her

  20. Diphenylarsinic acid contaminated soil remediation by titanium dioxide (P25) photocatalysis: Degradation pathway, optimization of operating parameters and effects of soil properties

    Energy Technology Data Exchange (ETDEWEB)

    Wang, A-nan [Key Laboratory of Soil Environment and Pollution Remediation, Institute of Soil Science, Chinese Academy of Sciences, Nanjing 210008 (China); Graduate School of Chinese Academy of Sciences, Beijing 100039 (China); Teng, Ying [Key Laboratory of Soil Environment and Pollution Remediation, Institute of Soil Science, Chinese Academy of Sciences, Nanjing 210008 (China); Hu, Xue-feng [Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai 264003 (China); Wu, Long-hua; Huang, Yu-juan [Key Laboratory of Soil Environment and Pollution Remediation, Institute of Soil Science, Chinese Academy of Sciences, Nanjing 210008 (China); Luo, Yong-ming, E-mail: ymluo@yic.ac.cn [Key Laboratory of Soil Environment and Pollution Remediation, Institute of Soil Science, Chinese Academy of Sciences, Nanjing 210008 (China); Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai 264003 (China); Christie, Peter [Key Laboratory of Soil Environment and Pollution Remediation, Institute of Soil Science, Chinese Academy of Sciences, Nanjing 210008 (China)

    2016-01-15

    Diphenylarsinic acid (DPAA) is formed during the leakage of arsenic chemical weapons in sites and poses a high risk to biota. However, remediation methods for DPAA contaminated soils are rare. Here, the photocatalytic oxidation (PCO) process by nano-sized titanium dioxide (TiO{sub 2}) was applied to degrade DPAA in soil. The degradation pathway was firstly studied, and arsenate was identified as the final product. Then, an orthogonal array experimental design of L{sub 9}(3){sup 4}, only 9 experiments were needed, instead of 81 experiments in a conventional one-factor-at-a-time, was used to optimize the operational parameters soil:water ratio, TiO{sub 2} dosage, irradiation time and light intensity to increase DPAA removal efficiency. Soil:water ratio was found to have a more significant effect on DPAA removal efficiency than other properties. The optimum conditions to treat 4 g soil with a DPAA concentration of 20 mg kg{sup −1} were found to be a 1:10 soil: water ratio, 40 mW cm{sup −2} light intensity, 5% TiO{sub 2} in soil, and a 3-hour irradiation time, with a removal efficiency of up to 82.7%. Furthermore, this method (except for a change in irradiation time from 3 to 1.5 h) was validated in nine different soils and the removal efficiencies ranged from 57.0 to 78.6%. Removal efficiencies were found to be negatively correlated with soil electrical conductivity, organic matter content, pH and total phosphorus content. Finally, coupled with electron spin resonance (ESR) measurement, these soil properties affected the generation of OH• by TiO{sub 2} in soil slurry. This study suggests that TiO{sub 2} photocatalytic oxidation is a promising treatment for removing DPAA from soil. - Highlights: • DPAA was degraded into arsenate through TiO{sub 2} (P25) photocatalytic oxidation. • Soil/water ratio was more influential on the removal of DPAA in soil by TiO{sub 2} (P25). • Soil properties affected the adsorption of DPAA and the generation of OH• by Ti

  1. Rinderpest: the veterinary perspective on eradication.

    Science.gov (United States)

    Roeder, Peter; Mariner, Jeffrey; Kock, Richard

    2013-08-05

    Rinderpest was a devastating disease of livestock responsible for continent-wide famine and poverty. Centuries of veterinary advances culminated in 2011 with the UN Food and Agriculture Organization and the World Organization for Animal Health declaring global eradication of rinderpest; only the second disease to be eradicated and the greatest veterinary achievement of our time. Conventional control measures, principally mass vaccination combined with zoosanitary procedures, led to substantial declines in the incidence of rinderpest. However, during the past decades, innovative strategies were deployed for the last mile to overcome diagnostic and surveillance challenges, unanticipated variations in virus pathogenicity, circulation of disease in wildlife populations and to service remote and nomadic communities in often-unstable states. This review provides an overview of these challenges, describes how they were overcome and identifies key factors for this success.

  2. A putrescine-inducible pathway comprising PuuE-YneI in which gamma-aminobutyrate is degraded into succinate in Escherichia coli K-12.

    Science.gov (United States)

    Kurihara, Shin; Kato, Kenji; Asada, Kei; Kumagai, Hidehiko; Suzuki, Hideyuki

    2010-09-01

    Gamma-aminobutyrate (GABA) is metabolized to succinic semialdehyde by GABA aminotransferase (GABA-AT), and the succinic semialdehyde is subsequently oxidized to succinate by succinic semialdehyde dehydrogenase (SSADH). In Escherichia coli, there are duplicate GABA-ATs (GabT and PuuE) and duplicate SSADHs (GabD and YneI). While GabT and GabD have been well studied previously, the characterization and expression analysis of PuuE and YneI are yet to be investigated. By analyzing the amino acid profiles in cells of DeltapuuE and/or DeltagabT mutants, this study demonstrated that PuuE plays an important role in GABA metabolism in E. coli cells. The similarity of the amino acid sequences of PuuE and GabT is 67.4%, and it was biochemically demonstrated that the catalytic center of GabT is conserved as an amino acid residue important for the enzymatic activity in PuuE as Lys-247. However, the regulation of expression of PuuE is significantly different from that of GabT. PuuE is induced by the addition of putrescine to the medium and is repressed by succinate and low aeration conditions; in contrast, GabT is almost constitutive. Similarly, YneI is induced by putrescine, while GabD is not. For E. coli, PuuE is important for utilization of putrescine as a sole nitrogen source and both PuuE and YneI are important for utilization of putrescine as a sole carbon source. The results demonstrate that the PuuE-YneI pathway was a putrescine-inducible GABA degradation pathway for utilizing putrescine as a nutrient source.

  3. China’s Polio Eradication Campaign

    Institute of Scientific and Technical Information of China (English)

    JANE; SHAW

    1995-01-01

    DECEMBER 5. 1993 was the first Intensive Immunization Day for eradicating poliomyelitis in China. On this day. Chinese President Jiang Zemin and other state leaders went to hospitals to help give children under the age of 4 the oral polio vaccine. Jiang Zemin gave the inscription: "Popularize Children’s Immunization, Dedicate a Loving Heart to Children." December 5, 1994 was the second Intensive Immunization Day. On this day,

  4. [Update on the dracunculosis eradication program].

    Science.gov (United States)

    Ranque, P; Peries, H; Meert, J P; O'Neill, K

    1996-01-01

    Dracunculiasis has been described since antiquity and will be forever associated with the image of the method of extraction consisting of winding a few centimeters of the worm around a stick every day. For nearly ten years a worldwide effort to eradicate this infection has been under way. Achieving this apparently simple goal is hindered by the difficulties in accessing infected areas and by the dire poverty in the regions involved which include the "poorest of the poor". Spectacular results have been accomplished in Pakistan thanks to the concerted efforts of political, financial, and technical officials from a number of national and international organization. While the rate of infestation has decreased by 90% worldwide, the final push to complete eradication is the most difficult and, as in India and Mali, is being oriented towards a strategy involving an integrated approach. Results are slow and gradual but notable and durable progress has been made in terms of village water supply. It is necessary that intervention in these areas be associated with other poverty-fighting programs. Successful eradication without accompanying improvements would be a technical victory but in terms of public health and welfare such a victory would correspond to an unjustifiably missed opportunity.

  5. So close: remaining challenges to eradicating polio.

    Science.gov (United States)

    Toole, Michael J

    2016-03-14

    The Global Polio Eradication Initiative, launched in 1988, is close to achieving its goal. In 2015, reported cases of wild poliovirus were limited to just two countries - Afghanistan and Pakistan. Africa has been polio-free for more than 18 months. Remaining barriers to global eradication include insecurity in areas such as Northwest Pakistan and Eastern and Southern Afghanistan, where polio cases continue to be reported. Hostility to vaccination is either based on extreme ideologies, such as in Pakistan, vaccination fatigue by parents whose children have received more than 15 doses, and misunderstandings about the vaccine's safety and effectiveness such as in Ukraine. A further challenge is continued circulation of vaccine-derived poliovirus in populations with low immunity, with 28 cases reported in 2015 in countries as diverse as Madagascar, Ukraine, Laos, and Myanmar. This paper summarizes the current epidemiology of wild and vaccine-derived poliovirus, and describes the remaining challenges to eradication and innovative approaches being taken to overcome them.

  6. A research agenda for malaria eradication: vaccines.

    Science.gov (United States)

    2011-01-25

    Vaccines could be a crucial component of efforts to eradicate malaria. Current attempts to develop malaria vaccines are primarily focused on Plasmodium falciparum and are directed towards reducing morbidity and mortality. Continued support for these efforts is essential, but if malaria vaccines are to be used as part of a repertoire of tools for elimination or eradication of malaria, they will need to have an impact on malaria transmission. We introduce the concept of "vaccines that interrupt malaria transmission" (VIMT), which includes not only "classical" transmission-blocking vaccines that target the sexual and mosquito stages but also pre-erythrocytic and asexual stage vaccines that have an effect on transmission. VIMT may also include vaccines that target the vector to disrupt parasite development in the mosquito. Importantly, if eradication is to be achieved, malaria vaccine development efforts will need to target other malaria parasite species, especially Plasmodium vivax, where novel therapeutic vaccines against hypnozoites or preventive vaccines with effect against multiple stages could have enormous impact. A target product profile (TPP) for VIMT is proposed and a research agenda to address current knowledge gaps and develop tools necessary for design and development of VIMT is presented.

  7. High quality draft genome sequence of Olivibacter sitiensis type strain (AW-6(T)), a diphenol degrader with genes involved in the catechol pathway.

    Science.gov (United States)

    Ntougias, Spyridon; Lapidus, Alla; Han, James; Mavromatis, Konstantinos; Pati, Amrita; Chen, Amy; Klenk, Hans-Peter; Woyke, Tanja; Fasseas, Constantinos; Kyrpides, Nikos C; Zervakis, Georgios I

    2014-06-15

    Olivibacter sitiensis Ntougias et al. 2007 is a member of the family Sphingobacteriaceae, phylum Bacteroidetes. Members of the genus Olivibacter are phylogenetically diverse and of significant interest. They occur in diverse habitats, such as rhizosphere and contaminated soils, viscous wastes, composts, biofilter clean-up facilities on contaminated sites and cave environments, and they are involved in the degradation of complex and toxic compounds. Here we describe the features of O. sitiensis AW-6(T), together with the permanent-draft genome sequence and annotation. The organism was sequenced under the Genomic Encyclopedia for Bacteria and Archaea (GEBA) project at the DOE Joint Genome Institute and is the first genome sequence of a species within the genus Olivibacter. The genome is 5,053,571 bp long and is comprised of 110 scaffolds with an average GC content of 44.61%. Of the 4,565 genes predicted, 4,501 were protein-coding genes and 64 were RNA genes. Most protein-coding genes (68.52%) were assigned to a putative function. The identification of 2-keto-4-pentenoate hydratase/2-oxohepta-3-ene-1,7-dioic acid hydratase-coding genes indicates involvement of this organism in the catechol catabolic pathway. In addition, genes encoding for β-1,4-xylanases and β-1,4-xylosidases reveal the xylanolytic action of O. sitiensis.

  8. The Drosophila insulin-degrading enzyme restricts growth by modulating the PI3K pathway in a cell-autonomous manner.

    Science.gov (United States)

    Galagovsky, Diego; Katz, Maximiliano J; Acevedo, Julieta M; Sorianello, Eleonora; Glavic, Alvaro; Wappner, Pablo

    2014-03-01

    Mammalian insulin-degrading enzyme (IDE) cleaves insulin, among other peptidic substrates, but its function in insulin signaling is elusive. We use the Drosophila system to define the function of IDE in the regulation of growth and metabolism. We find that either loss or gain of function of Drosophila IDE (dIDE) can restrict growth in a cell-autonomous manner by affecting both cell size and cell number. dIDE can modulate Drosophila insulin-like peptide 2 levels, thereby restricting activation of the phosphatidylinositol-3-phosphate kinase pathway and promoting activation of Drosophila forkhead box, subgroup O transcription factor. Larvae reared in high sucrose exhibit delayed developmental timing due to insulin resistance. We find that dIDE loss of function exacerbates this phenotype and that mutants display increased levels of circulating sugar, along with augmented expression of a lipid biosynthesis marker. We propose that dIDE is a modulator of insulin signaling and that its loss of function favors insulin resistance, a hallmark of diabetes mellitus type II.

  9. Degradation of di(2-ethyl hexyl) phthalate by Fusarium culmorum: Kinetics, enzymatic activities and biodegradation pathway based on quantum chemical modelingpathway based on quantum chemical modeling.

    Science.gov (United States)

    Ahuactzin-Pérez, Miriam; Tlecuitl-Beristain, Saúl; García-Dávila, Jorge; González-Pérez, Manuel; Gutiérrez-Ruíz, María Concepción; Sánchez, Carmen

    2016-10-01

    Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer widely used in the manufacture of plastics, and it is an environmental contaminant. The specific growth rate (μ), maximum biomass (Xmax), biodegradation constant of DEHP (k), half-life (t1/2) of DEHP biodegradation and removal efficiency of DEHP, esterase and laccase specific activities, and enzymatic yield parameters were evaluated for Fusarium culmorum grown on media containing glucose and different concentrations of DEHP (0, 500 and 1000mg/L). The greatest μ and the largest Xmax occurred in media supplemented with 1000mg of DEHP/L. F. culmorum degraded 95% of the highest amount of DEHP tested (1000mg/L) within 60h of growth. The k and t1/2 were 0.024h(-1) and 28h, respectively, for both DEHP concentrations. The removal efficiency of DEHP was 99.8% and 99.9% for 1000 and 500mg/L, respectively. Much higher specific esterase activity than specific laccase activity was observed in all media tested. The compounds of biodegradation of DEHP were identified by GC-MS. A DEHP biodegradation pathway by F. culmorum was proposed on the basis of the intermolecular flow of electrons of the identified intermediate compounds using quantum chemical modeling. DEHP was fully metabolized by F. culmorum with butanediol as the final product. This fungus offers great potential in bioremediation of environments polluted with DEHP.

  10. The threonine degradation pathway of the Trypanosoma brucei procyclic form: the main carbon source for lipid biosynthesis is under metabolic control.

    Science.gov (United States)

    Millerioux, Yoann; Ebikeme, Charles; Biran, Marc; Morand, Pauline; Bouyssou, Guillaume; Vincent, Isabel M; Mazet, Muriel; Riviere, Loïc; Franconi, Jean-Michel; Burchmore, Richard J S; Moreau, Patrick; Barrett, Michael P; Bringaud, Frédéric

    2013-10-01

    The Trypanosoma brucei procyclic form resides within the digestive tract of its insect vector, where it exploits amino acids as carbon sources. Threonine is the amino acid most rapidly consumed by this parasite, however its role is poorly understood. Here, we show that the procyclic trypanosomes grown in rich medium only use glucose and threonine for lipid biosynthesis, with threonine's contribution being ∼ 2.5 times higher than that of glucose. A combination of reverse genetics and NMR analysis of excreted end-products from threonine and glucose metabolism, shows that acetate, which feeds lipid biosynthesis, is also produced primarily from threonine. Interestingly, the first enzymatic step of the threonine degradation pathway, threonine dehydrogenase (TDH, EC 1.1.1.103), is under metabolic control and plays a key role in the rate of catabolism. Indeed, a trypanosome mutant deleted for the phosphoenolpyruvate decarboxylase gene (PEPCK, EC 4.1.1.49) shows a 1.7-fold and twofold decrease of TDH protein level and activity, respectively, associated with a 1.8-fold reduction in threonine-derived acetate production. We conclude that TDH expression is under control and can be downregulated in response to metabolic perturbations, such as in the PEPCK mutant in which the glycolytic metabolic flux was redirected towards acetate production.

  11. The Quest for Converting Biorenewable Bifunctional α-Methylene-γ-butyrolactone into Degradable and Recyclable Polyester: Controlling Vinyl-Addition/Ring-Opening/Cross-Linking Pathways

    KAUST Repository

    Tang, Xiaoyan

    2016-10-04

    α-Methylene-γ-butyrolactone (MBL), a naturally occurring and biomass-sourced bifunctional monomer, contains both a highly reactive exocyclic C═C bond and a highly stable five-membered γ-butyrolactone ring. Thus, all previous work led to exclusive vinyl-addition polymerization (VAP) product P(MBL)VAP. Now, this work reverses this conventional chemoselectivity to enable the first ring-opening polymerization (ROP) of MBL, thereby producing exclusively unsaturated polyester P(MBL)ROP with Mn up to 21.0 kg/mol. This elusive goal was achieved through uncovering the thermodynamic, catalytic, and processing conditions. A third reaction pathway has also been discovered, which is a crossover propagation between VAP and ROP processes, thus affording cross-linked polymer P(MBL)CLP. The formation of the three types of polymers, P(MBL)VAP, P(MBL)CLP, and P(MBL)ROP, can be readily controlled by adjusting the catalyst (La)/initiator (ROH) ratio, which is determined by the unique chemoselectivity of the La–X (X = OR, NR2, R) group. The resulting P(MBL)ROP is degradable and can be readily postfunctionalized into cross-linked or thiolated materials but, more remarkably, can also be fully recycled back to its monomer thermochemically. Computational studies provided the theoretical basis for, and a mechanistic understanding of, the three different polymerization processes and the origin of the chemoselectivity.

  12. High quality draft genome sequence of Olivibacter sitiensis type strain (AW-6T), a diphenol degrader with genes involved in the catechol pathway

    Science.gov (United States)

    Ntougias, Spyridon; Lapidus, Alla; Han, James; Mavromatis, Konstantinos; Pati, Amrita; Chen, Amy; Klenk, Hans-Peter; Woyke, Tanja; Fasseas, Constantinos; Kyrpides, Nikos C.; Zervakis, Georgios I.

    2014-01-01

    Olivibacter sitiensis Ntougias et al. 2007 is a member of the family Sphingobacteriaceae, phylum Bacteroidetes. Members of the genus Olivibacter are phylogenetically diverse and of significant interest. They occur in diverse habitats, such as rhizosphere and contaminated soils, viscous wastes, composts, biofilter clean-up facilities on contaminated sites and cave environments, and they are involved in the degradation of complex and toxic compounds. Here we describe the features of O. sitiensis AW-6T, together with the permanent-draft genome sequence and annotation. The organism was sequenced under the Genomic Encyclopedia for Bacteria and Archaea (GEBA) project at the DOE Joint Genome Institute and is the first genome sequence of a species within the genus Olivibacter. The genome is 5,053,571 bp long and is comprised of 110 scaffolds with an average GC content of 44.61%. Of the 4,565 genes predicted, 4,501 were protein-coding genes and 64 were RNA genes. Most protein-coding genes (68.52%) were assigned to a putative function. The identification of 2-keto-4-pentenoate hydratase/2-oxohepta-3-ene-1,7-dioic acid hydratase-coding genes indicates involvement of this organism in the catechol catabolic pathway. In addition, genes encoding for β-1,4-xylanases and β-1,4-xylosidases reveal the xylanolytic action of O. sitiensis. PMID:25197463

  13. Heterogeneous photo-Fenton decolorization of Orange II over Al-pillared Fe-smectite: response surface approach, degradation pathway, and toxicity evaluation.

    Science.gov (United States)

    Li, Huiyuan; Li, Yanli; Xiang, Luojing; Huang, Qianqian; Qiu, Juanjuan; Zhang, Hui; Sivaiah, Matte Venkata; Baron, Fabien; Barrault, Joel; Petit, Sabine; Valange, Sabine

    2015-04-28

    A ferric smectite clay material was synthesized and further intercalated with Al2O3 pillars for the first time with the aim of evaluating its ability to be used as heterogeneous catalyst for the photo-Fenton decolorization of azo dye Orange II. UV irradiation was found to enhance the activity of the catalyst in the heterogeneous photo-Fenton process. Catalyst loading of 0.5g/L and hydrogen peroxide concentration of 13.5mM yielded a remarkable color removal, accompanied by excellent catalyst stability. The decolorization of Orange II followed the pseudo-first-order kinetics for initial dye concentrations from 20 to 160mg/L. The central composite design (CCD) based on the response surface methodology (RSM) was applied to evaluate the effects of several operating parameters, namely initial pH, catalyst loading and hydrogen peroxide concentration, on the decolorization efficiency. The RSM model was derived and the response surface plots were developed based on the results. Moreover, the main intermediate products were separated and identified using gas chromatography-mass spectrometry (GC-MS) and a possible degradation pathway was proposed accordingly. The acute toxicity experiments illustrated that the Daphniamagna immobilization rate continuously decreased during 150min reaction, indicating that the effluent was suitable for sequential biological treatment. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. The role of research in viral disease eradication and elimination programs: lessons for malaria eradication.

    Directory of Open Access Journals (Sweden)

    Joel G Breman

    Full Text Available By examining the role research has played in eradication or regional elimination initiatives for three viral diseases--smallpox, poliomyelitis, and measles--we derive nine cross-cutting lessons applicable to malaria eradication. In these initiatives, some types of research commenced as the programs began and proceeded in parallel. Basic laboratory, clinical, and field research all contributed notably to progress made in the viral programs. For each program, vaccine was the lynchpin intervention, but as the programs progressed, research was required to improve vaccine formulations, delivery methods, and immunization schedules. Surveillance was fundamental to all three programs, whilst polio eradication also required improved diagnostic methods to identify asymptomatic infections. Molecular characterization of pathogen isolates strengthened surveillance and allowed insights into the geographic source of infections and their spread. Anthropologic, sociologic, and behavioural research were needed to address cultural and religious beliefs to expand community acceptance. The last phases of elimination and eradication became increasingly difficult, as a nil incidence was approached. Any eradication initiative for malaria must incorporate flexible research agendas that can adapt to changing epidemiologic contingencies and allow planning for posteradication scenarios.

  15. Apigenin induces apoptosis through proteasomal degradation of HER2/neu in HER2/neu-overexpressing breast cancer cells via the phosphatidylinositol 3-kinase/Akt-dependent pathway.

    Science.gov (United States)

    Way, Tzong-Der; Kao, Ming-Ching; Lin, Jen-Kun

    2004-02-06

    Apigenin is a low toxicity and non-mutagenic phytopolyphenol and protein kinase inhibitor. It exhibits anti-proliferating effects on human breast cancer cells. Here we examined several human breast cancer cell lines having different levels of HER2/neu expression and found that apigenin exhibited potent growth-inhibitory activity in HER2/neu-overexpressing breast cancer cells but was much less effective for those cells expressing basal levels of HER2/neu. Induction of apoptosis was also observed in HER2/neu-overexpressing breast cancer cells in a dose- and time-dependent manner. However, the one or more molecular mechanisms of apigenin-induced apoptosis in HER2/neu-overexpressing breast cancer cells remained to be elucidated. A cell survival pathway involving phosphatidylinositol 3-kinase (PI3K), and Akt is known to play an important role in inhibiting apoptosis in response to HER2/neu-overexpressing breast cancer cells, which prompted us to investigate whether this pathway plays a role in apigenin-induced apoptosis in HER2/neu-overexpressing breast cancer cells. Our results showed that apigenin inhibits Akt function in tumor cells in a complex manner. First, apigenin directly inhibited the PI3K activity while indirectly inhibiting the Akt kinase activity. Second, inhibition of HER2/neu autophosphorylation and transphosphorylation resulting from depleting HER2/neu protein in vivo was also observed. In addition, apigenin inhibited Akt kinase activity by preventing the docking of PI3K to HER2/HER3 heterodimers. Therefore, we proposed that apigenin-induced cellular effects result from loss of HER2/neu and HER3 expression with subsequent inactivation of PI3K and AKT in cells that are dependent on this pathway for cell proliferation and inhibition of apoptosis. This implies that the inhibition of the HER2/HER3 heterodimer function provided an especially effective strategy for blocking the HER2/neu-mediated transformation of breast cancer cells. Our results also

  16. Isolation of the phe-operon from G. stearothermophilus comprising the phenol degradative meta-pathway genes and a novel transcriptional regulator

    Directory of Open Access Journals (Sweden)

    Reiss Monika

    2008-11-01

    Full Text Available Abstract Background Geobacillus stearothermophilus is able to utilize phenol as a sole carbon source. A DNA fragment encoding a phenol hydroxylase catalyzing the first step in the meta-pathway has been isolated previously. Based on these findings a PCR-based DNA walk was performed initially to isolate a catechol 2,3-dioxygenase for biosensoric applications but was continued to elucidate the organisation of the genes encoding the proteins for the metabolization of phenol. Results A 20.2 kb DNA fragment was isolated as a result of the DNA walk. Fifteen open reading frames residing on a low-copy megaplasmid were identified. Eleven genes are co-transcribed in one polycistronic mRNA as shown by reverse transcription-PCR. Ten genes encode proteins, that are directly linked with the meta-cleavage pathway. The deduced amino acid sequences display similarities to a two-component phenol hydroxylase, a catechol 2,3-dioxygenase, a 4-oxalocrotonate tautomerase, a 2-oxopent-4-dienoate hydratase, a 4-oxalocrotonate decarboxylase, a 4-hydroxy-2-oxovalerate aldolase, an acetaldehyde dehydrogenase, a plant-type ferredoxin involved in the reactivation of extradiol dioxygenases and a novel regulatory protein. The only enzymes missing for the complete mineralization of phenol are a 2-hydroxymuconic acid-6-semialdehyde hydrolase and/or 2-hydroxymuconic acid-6-semialdehyde dehydrogenase. Conclusion Research on the bacterial degradation of aromatic compounds on a sub-cellular level has been more intensively studied in gram-negative organisms than in gram-positive bacteria. Especially regulatory mechanisms in gram-positive (thermophilic prokaryotes remain mostly unknown. We isolated the first complete sequence of an operon from a thermophilic bacterium encoding the meta-pathway genes and analyzed the genetic organization. Moreover, the first transcriptional regulator of the phenol metabolism in gram-positive bacteria was identified. This is a first step to elucidate

  17. Efficient degradation of TCE in groundwater using Pd and electro-generated H2 and O2: a shift in pathway from hydrodechlorination to oxidation in the presence of ferrous ions.

    Science.gov (United States)

    Yuan, Songhu; Mao, Xuhui; Alshawabkeh, Akram N

    2012-03-20

    Degradation of trichloroethylene (TCE) in simulated groundwater by Pd and electro-generated H(2) and O(2) is investigated in the absence and presence of Fe(II). In the absence of Fe(II), hydrodechlorination dominates TCE degradation, with accumulation of H(2)O(2) up to 17 mg/L. Under weak acidity, low concentrations of oxidizing •OH radicals are detected due to decomposition of H(2)O(2), slightly contributing to TCE degradation via oxidation. In the presence of Fe(II), the degradation efficiency of TCE at 396 μM improves to 94.9% within 80 min. The product distribution proves that the degradation pathway shifts from 79% hydrodechlorination in the absence of Fe(II) to 84% •OH oxidation in the presence of Fe(II). TCE degradation follows zeroth-order kinetics with rate constants increasing from 2.0 to 4.6 μM/min with increasing initial Fe(II) concentration from 0 to 27.3 mg/L at pH 4. A good correlation between TCE degradation rate constants and •OH generation rate constants confirms that •OH is the predominant reactive species for TCE oxidation. Presence of 10 mM Na(2)SO(4), NaCl, NaNO(3), NaHCO(3), K(2)SO(4), CaSO(4), and MgSO(4) does not significantly influence degradation, but sulfite and sulfide greatly enhance and slightly suppress degradation, respectively. A novel Pd-based electrochemical process is proposed for groundwater remediation.

  18. Batteries: Imaging degradation

    Science.gov (United States)

    Shearing, Paul R.

    2016-11-01

    The degradation and failure of Li-ion batteries is strongly associated with electrode microstructure change upon (de)lithiation. Now, an operando X-ray tomography approach is shown to correlate changes in the microstructure of electrodes to cell performance, and thereby predict degradation pathways.

  19. Eradicating Corruption in Public Office in Nigeria

    Directory of Open Access Journals (Sweden)

    Wada Attah Ademu

    2013-12-01

    Full Text Available This paper attempts to provide a model for dealing with the problem of corruption in Nigeria. It uses an analytical approach to explore the Singapore model of dealing with acts of corruption to serve as a model for Nigeria. Corruption is inimical to socio-economic development of any country where it is practised on any scale. This explains why all nations make efforts to minimize or eradicate corruption in their economies. Nigeria has been ranked among the most corrupt nations of the World by many international anti-corruption agencies. If other nations take measures to eradicate corruption from their economies because of its negative consequences, Nigeria cannot be an exception. Corruption has led to gross misuse of public funds in Nigeria and has caused untold hardship to her citizens via non-payments of people’s benefits and lack of provision of basic public utilities. To deal with corruption in Nigeria, various anti-corruption agencies were set up but the problem remains. This paper therefore recommends the Singapore model as a method of dealing with corruption in Nigeria. This model holds each sectional head responsible for any act of corruption in his/her unit if established. The government was strong and determined to deal with the transgressors; there was political will to tame corruption and therefore there was government support to the anti-corruption agencies. If this model is adopted and faithfully implemented, corruption could be eradicated from Nigeria. In addition, constitutional amendments that would update and clearly define acts that constitute corrupt practices as these acts manifest in various forms are necessary to facilitate interpretation and enforcement of anti-corruption laws.

  20. Measuring Poverty in order to Eradicate It

    Directory of Open Access Journals (Sweden)

    Julien Damon

    2012-06-01

    Full Text Available In 2000, the UN established its Millennium Development Goals, with the notable aim of halving extreme poverty by 2015. That same year, the European Union launched its Lisbon strategy, containing an injunction to “make a decisive impact on the eradication of poverty by 2010”. Since 2007, France has set a national target of reducing poverty by one third over five years. These proactive policies call, in all three cases, for technical elucidation to define and describe poverty. Each of the three scales – French, European and international – has its own approaches and methods of quantification. And yet their similarities are more significant than their differences.

  1. Hybrid Therapy Regimen for Helicobacter Pylori Eradication

    Institute of Scientific and Technical Information of China (English)

    Zhi-Qiang Song; Jian Liu; Li-Ya Zhou

    2016-01-01

    Objective:Helicobacterpylori (H.pylori) eradication remains a challenge with increasing antibiotic resistance.Hybrid therapy has attracted widespread attention because of initial report with good efficacy and safety.However,many issues on hybrid therapy are still unclear such as the eradication efficacy,safety,compliance,influencing factors,correlation with antibiotic resistance,and comparison with other regimens.Therefore,a comprehensive review on the evidence of hybrid therapy for H.pylori infection was conducted.Data Sources:The data used in this review were mainly from PubMed articles published in English up to September 30,2015,searching by the terms of"Helicobacterpylori" or "H.pylori",and "hybrid".Study Selection:Clinical research articles were selected mainly according to their level of relevance to this topic.Results:Totally,1871 patients of 12 studies received hybrid therapy.The eradication rates were 77.6-97.4% in intention-to-treat and 82.6-99.1% in per-protocol analyses.Compliance was 93.3-100.0%,overall adverse effects rate was 14.5-67.5%,and discontinued medication rate due to adverse effects was 0-6.7%.H.pylori culture and sensitivity test were performed only in 13.3% patients.Pooled analysis showed that the eradication rates with dual clarithromycin and metronidazole susceptible,isolated metronidazole or clarithromycin resistance,and dual clarithromycin and metronidazole resistance were 98.5%,97.6%,92.9%,and 80.0%,respectively.Overall,the efficacy,compliance,and safety of hybrid therapy were similar with sequential or concomitant therapy.However,hybrid therapy might be superior to sequential therapy in Asians.Conclusions:Hybrid therapy showed wide differences in the efficacy but consistently good compliance and safety across different regions.Dual clarithromycin and metronidazole resistance were the key factor to efficacy.Hybrid therapy was similar to sequential or concomitant therapy in the efficacy,safety,and compliance.

  2. Disulfiram/copper-disulfiram Damages Multiple Protein Degradation and Turnover Pathways and Cytotoxicity is Enhanced by Metformin in Oesophageal Squamous Cell Carcinoma Cell Lines.

    Science.gov (United States)

    Jivan, Rupal; Damelin, Leonard Howard; Birkhead, Monica; Rousseau, Amanda Louise; Veale, Robin Bruce; Mavri-Damelin, Demetra

    2015-10-01

    Disulfiram (DSF), used since the 1950s in the treatment of alcoholism, is reductively activated to diethyldithiocarbamate and both compounds are thiol-reactive and readily complex copper. More recently DSF and copper-DSF (Cu-DSF) have been found to exhibit potent anticancer activity. We have previously shown that the anti-diabetic drug metformin is anti-proliferative and induces an intracellular reducing environment in oesophageal squamous cell carcinoma (OSCC) cell lines. Based on these observations, we investigated the effects of Cu-DSF and DSF, with and without metformin, in this present study. We found that Cu-DSF and DSF caused considerable cytotoxicity across a panel of OSCC cells, and metformin significantly enhanced the effects of DSF. Elevated copper transport contributes to DSF and metformin-DSF-induced cytotoxicity since the cell-impermeable copper chelator, bathocuproinedisulfonic acid, partially reversed the cytotoxic effects of these drugs, and interestingly, metformin-treated OSCC cells contained higher intracellular copper levels. Furthermore, DSF may target cancer cells preferentially due to their high dependence on protein degradation/turnover pathways, and we found that metformin further enhances the role of DSF as a proteasome inhibitor. We hypothesized that the lysosome could be an additional, novel, target of DSF. Indeed, this acid-labile compound decreased lysosomal acidification, and DSF-metformin co-treatment interfered with the progression of autophagy in these cells. In summary, this is the first such report identifying the lysosome as a target of DSF and based on the considerable cytotoxic effects of DSF either alone or in the presence of metformin, in vitro, and we propose these as novel potential chemotherapeutic approaches for OSCC.

  3. Overexpression of alpha-synuclein at non-toxic levels increases dopaminergic cell death induced by copper exposure via modulation of protein degradation pathways.

    Science.gov (United States)

    Anandhan, Annadurai; Rodriguez-Rocha, Humberto; Bohovych, Iryna; Griggs, Amy M; Zavala-Flores, Laura; Reyes-Reyes, Elsa M; Seravalli, Javier; Stanciu, Lia A; Lee, Jaekwon; Rochet, Jean-Christophe; Khalimonchuk, Oleh; Franco, Rodrigo

    2015-09-01

    Gene multiplications or point mutations in alpha (α)-synuclein are associated with familial and sporadic Parkinson's disease (PD). An increase in copper (Cu) levels has been reported in the cerebrospinal fluid and blood of PD patients, while occupational exposure to Cu has been suggested to augment the risk to develop PD. We aimed to elucidate the mechanisms by which α-synuclein and Cu regulate dopaminergic cell death. Short-term overexpression of wild type (WT) or mutant A53T α-synuclein had no toxic effect in human dopaminergic cells and primary midbrain cultures, but it exerted a synergistic effect on Cu-induced cell death. Cell death induced by Cu was potentiated by overexpression of the Cu transporter protein 1 (Ctr1) and depletion of intracellular glutathione (GSH) indicating that the toxic effects of Cu are linked to alterations in its intracellular homeostasis. Using the redox sensor roGFP, we demonstrated that Cu-induced oxidative stress was primarily localized in the cytosol and not in the mitochondria. However, α-synuclein overexpression had no effect on Cu-induced oxidative stress. WT or A53T α-synuclein overexpression exacerbated Cu toxicity in dopaminergic and yeast cells in the absence of α-synuclein aggregation. Cu increased autophagic flux and protein ubiquitination. Impairment of autophagy by overexpression of a dominant negative Atg5 form or inhibition of the ubiquitin/proteasome system (UPS) with MG132 enhanced Cu-induced cell death. However, only inhibition of the UPS stimulated the synergistic toxic effects of Cu and α-synuclein overexpression. Our results demonstrate that α-synuclein stimulates Cu toxicity in dopaminergic cells independent from its aggregation via modulation of protein degradation pathways.

  4. Prokaryotic Homologs of the Eukaryotic 3-Hydroxyanthranilate 3,4-Dioxygenase and 2-Amino-3-Carboxymuconate-6-Semialdehyde Decarboxylase in the 2-Nitrobenzoate Degradation Pathway of Pseudomonas fluorescens Strain KU-7†

    OpenAIRE

    Muraki, Takamichi; Taki, Masami; Hasegawa, Yoshie; Iwaki, Hiroaki; Lau, Peter C. K.

    2003-01-01

    The 2-nitrobenzoic acid degradation pathway of Pseudomonas fluorescens strain KU-7 proceeds via a novel 3-hydroxyanthranilate intermediate. In this study, we cloned and sequenced a 19-kb DNA locus of strain KU-7 that encompasses the 3-hydroxyanthranilate meta-cleavage pathway genes. The gene cluster, designated nbaEXHJIGFCDR, is organized tightly and in the same direction. The nbaC and nbaD gene products were found to be novel homologs of the eukaryotic 3-hydroxyanthranilate 3,4-dioxygenase a...

  5. IRE1alpha is an endogenous substrate of endoplasmic reticulum-associated degradation

    NARCIS (Netherlands)

    Sun, Shengyi; Shi, Guojun; Sha, Haibo; Ji, Yewei; Han, Xuemei; Shu, Xin; Ma, Hongming; Takamasa, Inoue; Gao, Beixue; Bu, Pengcheng; Guber, Robert D.; Shen, Xiling; Lee, Ann H.; Iwawaki, Takao; Paton, Adrienne W.; Paton, James C.; Fang, Deyu; Tsai, Billy; Yates III, John R.; Wu, Haoquan; Kersten, Sander; Long, Qiaoming; Duhamel, Gerald E.; Simpson, Kenneth W.; Qi, Ling

    2015-01-01

    Endoplasmic reticulum-associated degradation (ERAD) represents a principle quality control (QC) mechanism to clear misfolded proteins in the ER; however, its physiological significance and the nature of endogenous ERAD substrates remain largely unknown. Here we discover that IRE1alpha, the sensor of

  6. Control and eradication of endemic infectious diseases in cattle

    DEFF Research Database (Denmark)

    Houe, Hans; Nielsen, Liza Rosenbaum; Nielsen, Søren Saxmose

    "Control and eradication of endemic infectious diseases in cattle" provides the key elements that should be addressed in the establishment of bovine disease control and eradication programmes. The book aims to reach a broad group of readers, including: students; professionals in veterinary practi......, industry and governmental institutions; researchers; and others involved in control and eradication of endemic diseases in livestock. Key elements range from socioeconomic aspects such as motivation; veterinary science (including assessment of biosecurity and establishment of test...

  7. Removal of antibiotic cloxacillin by means of electrochemical oxidation, TiO2 photocatalysis, and photo-Fenton processes: analysis of degradation pathways and effect of the water matrix on the elimination of antimicrobial activity.

    Science.gov (United States)

    Serna-Galvis, Efraim A; Giraldo-Aguirre, Ana L; Silva-Agredo, Javier; Flórez-Acosta, Oscar A; Torres-Palma, Ricardo A

    2017-03-01

    This study evaluates the treatment of the antibiotic cloxacillin (CLX) in water by means of electrochemical oxidation, TiO2 photocatalysis, and the photo-Fenton system. The three treatments completely removed cloxacillin and eliminated the residual antimicrobial activity from synthetic pharmaceutical wastewater containing the antibiotic, commercial excipients, and inorganic ions. However, significant differences in the degradation routes were found. In the photo-Fenton process, the hydroxyl radical was involved in the antibiotic removal, while in the TiO2 photocatalysis process, the action of both the holes and the adsorbed hydroxyl radicals degraded the pollutant. In the electrochemical treatment (using a Ti/IrO2 anode in sodium chloride as supporting electrolyte), oxidation via HClO played the main role in the removal of CLX. The analysis of initial by-products showed five different mechanistic pathways: oxidation of the thioether group, opening of the central β-lactam ring, breakdown of the secondary amide, hydroxylation of the aromatic ring, and decarboxylation. All the oxidation processes exhibited the three first pathways. Moreover, the aromatic ring hydroxylation was found in both photochemical treatments, while the decarboxylation of the pollutant was only observed in the TiO2 photocatalysis process. As a consequence of the degradation routes and mechanistic pathways, the elimination of organic carbon was different. After 480 and 240 min, the TiO2 photocatalysis and photo-Fenton processes achieved ∼45 and ∼15 % of mineralization, respectively. During the electrochemical treatment, 100 % of the organic carbon remained even after the antibiotic was treated four times the time needed to degrade it. In contrast, in all processes, a natural matrix (mineral water) did not considerably inhibit pollutant elimination. However, the presence of glucose in the water significantly affected the degradation of CLX by means of TiO2 photocatalysis.

  8. [Possible method of eradication of poliomyelitis as an infection].

    Science.gov (United States)

    Seĭbil', V B; Malyshkina, L P

    2012-01-01

    Problem of poliomyelitis eradication is examined in the review. After the eradication of wild poliovirus, vaccine poliomyelitis virus continues to circulate in the human population. In rare cases it can cause the development of the disease. The authors describe disadvantages of the use of oral and inactivated poliomyelitis vaccines and note that by using oral poliomyelitis vaccine and eradication only of wild poliovirus, eradication of poliomyelitis as an infection will not succeed. As one of the approaches to reach this goal the authors propose the use of various enterovirus interference. Use of live enterovirus vaccine is described and its advantages and disadvantages are examined.

  9. Age-dependent eradication of Helicobacter pylori in Japanese patients

    Science.gov (United States)

    Mamori, Satoshi; Higashida, Akihiro; Kawara, Fumiaki; Ohnishi, Katsuhiro; Takeda, Akihiko; Senda, Eri; Ashida, Cho; Yamada, Hajime

    2010-01-01

    AIM: To determine the general risk factors affecting the failure rate of first-line eradication therapy in Japanese patients with Helicobacter pylori (H. pylori) infection. METHODS: The present study enrolled 253 patients who had an H. pylori infection, underwent gastro-endoscopy, and were treated with H. pylori eradication therapy. Eradication therapy consisted of 30 mg lansoprazole plus 750 mg amoxicillin and 400 mg clarithromycin twice daily for 7 d. All of the patients underwent a 13C urea breath test at least 1 mo after the completion of eradication therapy. The current study investigated the independent factors associated with successful H. pylori eradication using a multiple logistic regression analysis. RESULTS: The overall success rate in the patients was 85.8%. Among the general factors examined in the multivariate analyses, only having an age less than 50 years was found to be significantly associated with a poor response to H. pylori eradication. Moreover, side effects were the only clinical factors in the patients who were under 50 years of age that significantly influenced the poor response to H. pylori eradication. CONCLUSION: H. pylori-positive elderly patients should undergo eradication therapy. In addition, it is necessary to improve H. pylori eradication therapy in younger patients. PMID:20806435

  10. Eradicating and eliminating infectious diseases: Past, Present and Future

    Directory of Open Access Journals (Sweden)

    Jai P Narain

    2011-01-01

    Full Text Available During the past 60 years, a number of infectious diseases have been targeted for eradication or elimination, with mixed results. While smallpox is the only one successfully eradicated so far, campaigns on yaws and malaria brought about a dramatic reduction in the incidence in the beginning of the campaign but ultimately could not achieve the desired goal. There is again a renewed interest in disease eradication. The World Health assembly in May 2010 passed a resolution calling for eradication of measles by 2015; the target of polio eradication still remains elusive. In view of these developments, it is appropriate time to revisit the concept of disease eradication and elimination, the achievements and failures of past eradication programmes and reasons thereof, and possibly apply these lessons while planning for the future activities. This paper based on the Dr. A.L.Saha Memorial Oration describes various infectious diseases that have been targeted for eradication or elimination since 1950s, the potential direct and indirect benefits from disease eradication, and the issues and opportunities for the future.

  11. Patchwork assembly of nag-like nitroarene dioxygenase genes and the 3-chlorocatechol degradation cluster for evolution of the 2-chloronitrobenzene catabolism pathway in Pseudomonas stutzeri ZWLR2-1.

    Science.gov (United States)

    Liu, Hong; Wang, Shu-Jun; Zhang, Jun-Jie; Dai, Hui; Tang, Huiru; Zhou, Ning-Yi

    2011-07-01

    Pseudomonas stutzeri ZWLR2-1 utilizes 2-chloronitrobenzene (2CNB) as a sole source of carbon, nitrogen, and energy. To identify genes involved in this pathway, a 16.2-kb DNA fragment containing putative 2CNB dioxygenase genes was cloned and sequenced. Of the products from the 19 open reading frames that resulted from this fragment, CnbAc and CnbAd exhibited striking identities to the respective α and β subunits of the Nag-like ring-hydroxylating dioxygenases involved in the metabolism of nitrotoluene, nitrobenzene, and naphthalene. The encoding genes were also flanked by two copies of insertion sequence IS6100. CnbAa and CnbAb are similar to the ferredoxin reductase and ferredoxin for anthranilate 1,2-dioxygenase from Burkholderia cepacia DBO1. Escherichia coli cells expressing cnbAaAbAcAd converted 2CNB to 3-chlorocatechol with concomitant nitrite release. Cell extracts of E. coli/pCNBC exhibited chlorocatechol 1,2-dioxygenase activity. The cnbCDEF gene cluster, homologous to a 3-chlorocatechol degradation cluster in Sphingomonas sp. strain TFD44, probably contains all of the genes necessary for the conversion of 3-chlorocatechol to 3-oxoadipate. The patchwork-like structure of this catabolic cluster suggests that the cnb cluster for 2CNB degradation evolved by recruiting two catabolic clusters encoding a nitroarene dioxygenase and a chlorocatechol degradation pathway. This provides another example to help elucidate the bacterial evolution of catabolic pathways in response to xenobiotic chemicals.

  12. Coronaviruses Hijack the LC3-I-positive EDEMosomes, ER-derived vesicles exporting short-lived ERAD regulators, for replication.

    Science.gov (United States)

    Reggiori, Fulvio; Monastyrska, Iryna; Verheije, Monique H; Calì, Tito; Ulasli, Mustafa; Bianchi, Siro; Bernasconi, Riccardo; de Haan, Cornelis A M; Molinari, Maurizio

    2010-06-25

    Coronaviruses (CoV), including SARS and mouse hepatitis virus (MHV), are enveloped RNA viruses that induce formation of double-membrane vesicles (DMVs) and target their replication and transcription complexes (RTCs) on the DMV-limiting membranes. The DMV biogenesis has been connected with the early secretory pathway. CoV-induced DMVs, however, lack conventional endoplasmic reticulum (ER) or Golgi protein markers, leaving their membrane origins in question. We show that MHV co-opts the host cell machinery for COPII-independent vesicular ER export of a short-living regulator of ER-associated degradation (ERAD), EDEM1, to derive cellular membranes for replication. MHV infection causes accumulation of EDEM1 and OS-9, another short-living ER chaperone, in the DMVs. DMVs are coated with the nonlipidated LC3/Atg8 autophagy marker. Downregulation of LC3, but not inactivation of host cell autophagy, protects cells from CoV infection. Our study identifies the host cellular pathway hijacked for supplying CoV replication membranes and describes an autophagy-independent role for nonlipidated LC3-I.

  13. Mutation of glutamic acid 103 of toluene o-xylene monooxygenase as a means to control the catabolic efficiency of a recombinant upper pathway for degradation of methylated aromatic compounds.

    Science.gov (United States)

    Cafaro, Valeria; Notomista, Eugenio; Capasso, Paola; Di Donato, Alberto

    2005-08-01

    Toluene o-xylene monooxygenase (ToMO) and phenol hydroxylase (PH) of Pseudomonas stutzeri OX1 act sequentially in a recombinant upper pathway for the degradation of aromatic hydrocarbons. The catalytic efficiency and regioselectivity of these enzymes optimize the degradation of growth substrates like toluene and o-xylene. For example, the sequential monooxygenation of o-xylene by ToMO and PH leads to almost exclusive production of 3,4-dimethylcatechol (3,4-DMC), the only isomer that can be further metabolized by the P. stutzeri meta pathway. We investigated the possibility of producing ToMO mutants with modified regioselectivity compared with the regioselectivity of the wild-type protein in order to alter the ability of the recombinant upper pathway to produce methylcatechol isomers from toluene and to produce 3,4-DMC from o-xylene. The combination of mutant (E103G)-ToMO and PH increased the production of 4-methylcatechol from toluene and increased the formation of 3,4-DMC from o-xylene. These data strongly support the idea that the products and efficiency of the metabolic pathway can be controlled not only through mutations that increase the catalytic efficiency of the enzymes involved but also through tuning the substrate specificity and regioselectivity of the enzymes. These findings are crucial for the development of future metabolic engineering strategies.

  14. Ordered bulk degradation via autophagy

    DEFF Research Database (Denmark)

    Dengjel, Jörn; Kristensen, Anders Riis; Andersen, Jens S

    2008-01-01

    at proteasomal and lysosomal degradation ample cross-talk between the two degradation pathways became evident. Degradation via autophagy appeared to be ordered and regulated at the protein complex/organelle level. This raises several important questions such as: can macroautophagy itself be specific and what...

  15. Mucoadhesive and muco-penetrating delivery systems for eradication of helicobacter pylori

    Directory of Open Access Journals (Sweden)

    Saahil Arora

    2012-01-01

    Full Text Available Helicobacter pylori (H. pylori, the major culprit for peptic ulcer, has a unique way of survival in harsh acidic environment of the stomach by colonizing deep in the gastric mucosal layer. Failure of conventional therapies against H. pylori for complete eradication has major limitations like low residence time of delivery system in stomach, poor penetration of drug in gastric mucosa, acidic degradation of antibiotics, and development of antibiotics resistance. The poor penetration of antibiotics through thick viscoelastic mucosal gel results in incomplete eradication of H. pylori. Various investigators have formulated novel gastro-retentive drug delivery systems such as floating systems, mucoadhesive systems, pH-sensitive gel systems, and muco-penetrating delivery systems for increasing the concentration of antibiotic in close proximity to the site of H. pylori infection. This review summarizes the novel drug delivery approaches investigated during the last few years and suggests that a high eradication rate can be achieved by therapy comprising of muco-penetrating delivery systems of antibiotics against H. pylori.

  16. Broadly Neutralizing Antibodies for HIV Eradication.

    Science.gov (United States)

    Stephenson, Kathryn E; Barouch, Dan H

    2016-02-01

    Passive transfer of antibodies has long been considered a potential treatment modality for infectious diseases, including HIV. Early efforts to use antibodies to suppress HIV replication, however, were largely unsuccessful, as the antibodies that were studied neutralized only a relatively narrow spectrum of viral strains and were not very potent. Recent advances have led to the discovery of a large portfolio of human monoclonal antibodies that are broadly neutralizing across many HIV-1 subtypes and are also substantially more potent. These antibodies target multiple different epitopes on the HIV envelope, thus allowing for the development of antibody combinations. In this review, we discuss the application of broadly neutralizing antibodies (bNAbs) for HIV treatment and HIV eradication strategies. We highlight bNAbs that target key epitopes, such as the CD4 binding site and the V2/V3-glycan-dependent sites, and we discuss several bNAbs that are currently in the clinical development pipeline.

  17. Tetracycline treatment does not eradicate Mycoplasma genitalium

    Science.gov (United States)

    Falk, L; Fredlund, H; Jensen, J

    2003-01-01

    Methods: All M genitalium positive patients (34 men and 26 women) attending an STD clinic during a 6 month period were treated with antibiotics. All patients known to be partners of M genitalium positive patients and those who were M genitalium positive, but not initially treated, were treated with azithromycin. Patients with urethritis and/or cervicitis were treated with tetracyclines before their M genitalium status was known. Results: 10 of 14 women (71%) and 10 of 16 men (63%) treated with tetracyclines were M genitalium positive at follow up, whereas all patients treated with azithromycin (16 men and 20 women) were M genitalium negative, at the 4 week follow up visit. Conclusions: These results suggest that tetracyclines are not sufficient to eradicate M genitalium. Randomised controlled treatment trials are urgently needed. PMID:12902584

  18. 76 FR 53165 - Certification Related to Aerial Eradication in Colombia

    Science.gov (United States)

    2011-08-25

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF STATE Certification Related to Aerial Eradication in Colombia Pursuant to the authority vested in the Secretary of... for aerial eradication of illicit crops in Colombia is being used in accordance with EPA...

  19. Gastric cancer development after the successful eradication of Helicobacter pylori

    Institute of Scientific and Technical Information of China (English)

    Kaname Uno; Katsunori Iijima; Tooru Shimosegawa

    2016-01-01

    Gastric cancer(GC) develops as a result of inflammationassociated carcinogenesis due to Helicobacter pylori(H. pylori) infection and subsequent defects in genetic/epigenetic events. Although the indication for eradication therapy has become widespread, clinical studies have revealed its limited effects in decreasing the incidence of GC. Moreover, research on biopsy specimens obtained by conventional endoscopy has demonstrated the feasibility of the restoration of some genetic/epigenetic alterations in the gastric mucosa. Practically, the number of sporadic cases of primary/metachronous GC that emerge after successful eradication has increased, while on-going guidelines recommend eradication therapy for patients with chronic gastritis and those with background mucosa after endoscopic resection for GC. Accordingly, regular surveillance of numerous individuals who have received eradication therapy is recommended despite the lack of biomarkers. Recently, the focus has been on functional reversibility after successful eradication as another cue to elucidate the mechanisms of restoration as well as those of carcinogenesis in the gastric mucosa after H. pylori eradication. We demonstrated that Congo-red chromoendoscopy enabled the identification of the multifocal distribution of functionally irreversible mucosa compared with that of restored mucosa after successful eradication in individuals at extremely high risk for GC. Further research that uses functional imaging may provide new insights into the mechanisms of regeneration and carcinogenesis in the gastric mucosa post-eradication and may allow for the development of useful biomarkers.

  20. Insect Eradication and Containment of Invasive Alien Species

    Science.gov (United States)

    Insect eradication programs are nearly always targeted at recently arrived invasive species with significant pest potential. They attempt to contain a pest to a defined area and then completely eliminate the pest from that area. From a Federal regulatory standpoint, eradication programs are undert...

  1. Gastric cancer development after the successful eradication of Helicobacter pylori.

    Science.gov (United States)

    Uno, Kaname; Iijima, Katsunori; Shimosegawa, Tooru

    2016-03-15

    Gastric cancer (GC) develops as a result of inflammation-associated carcinogenesis due to Helicobacter pylori (H. pylori) infection and subsequent defects in genetic/epigenetic events. Although the indication for eradication therapy has become widespread, clinical studies have revealed its limited effects in decreasing the incidence of GC. Moreover, research on biopsy specimens obtained by conventional endoscopy has demonstrated the feasibility of the restoration of some genetic/epigenetic alterations in the gastric mucosa. Practically, the number of sporadic cases of primary/metachronous GC that emerge after successful eradication has increased, while on-going guidelines recommend eradication therapy for patients with chronic gastritis and those with background mucosa after endoscopic resection for GC. Accordingly, regular surveillance of numerous individuals who have received eradication therapy is recommended despite the lack of biomarkers. Recently, the focus has been on functional reversibility after successful eradication as another cue to elucidate the mechanisms of restoration as well as those of carcinogenesis in the gastric mucosa after H. pylori eradication. We demonstrated that Congo-red chromoendoscopy enabled the identification of the multi-focal distribution of functionally irreversible mucosa compared with that of restored mucosa after successful eradication in individuals at extremely high risk for GC. Further research that uses functional imaging may provide new insights into the mechanisms of regeneration and carcinogenesis in the gastric mucosa post-eradication and may allow for the development of useful biomarkers.

  2. Invasive mammal eradication on islands results in substantial conservation gains.

    Science.gov (United States)

    Jones, Holly P; Holmes, Nick D; Butchart, Stuart H M; Tershy, Bernie R; Kappes, Peter J; Corkery, Ilse; Aguirre-Muñoz, Alfonso; Armstrong, Doug P; Bonnaud, Elsa; Burbidge, Andrew A; Campbell, Karl; Courchamp, Franck; Cowan, Philip E; Cuthbert, Richard J; Ebbert, Steve; Genovesi, Piero; Howald, Gregg R; Keitt, Bradford S; Kress, Stephen W; Miskelly, Colin M; Oppel, Steffen; Poncet, Sally; Rauzon, Mark J; Rocamora, Gérard; Russell, James C; Samaniego-Herrera, Araceli; Seddon, Philip J; Spatz, Dena R; Towns, David R; Croll, Donald A

    2016-04-12

    More than US$21 billion is spent annually on biodiversity conservation. Despite their importance for preventing or slowing extinctions and preserving biodiversity, conservation interventions are rarely assessed systematically for their global impact. Islands house a disproportionately higher amount of biodiversity compared with mainlands, much of which is highly threatened with extinction. Indeed, island species make up nearly two-thirds of recent extinctions. Islands therefore are critical targets of conservation. We used an extensive literature and database review paired with expert interviews to estimate the global benefits of an increasingly used conservation action to stem biodiversity loss: eradication of invasive mammals on islands. We found 236 native terrestrial insular faunal species (596 populations) that benefitted through positive demographic and/or distributional responses from 251 eradications of invasive mammals on 181 islands. Seven native species (eight populations) were negatively impacted by invasive mammal eradication. Four threatened species had their International Union for the Conservation of Nature (IUCN) Red List extinction-risk categories reduced as a direct result of invasive mammal eradication, and no species moved to a higher extinction-risk category. We predict that 107 highly threatened birds, mammals, and reptiles on the IUCN Red List-6% of all these highly threatened species-likely have benefitted from invasive mammal eradications on islands. Because monitoring of eradication outcomes is sporadic and limited, the impacts of global eradications are likely greater than we report here. Our results highlight the importance of invasive mammal eradication on islands for protecting the world's most imperiled fauna.

  3. Can we eradicate gastric MALT-lymphoma?

    Directory of Open Access Journals (Sweden)

    Angelo Zullo

    2013-04-01

    Full Text Available The incidence of primary gastric lymphoma in Italy is considerably higher than that observed in the rest of Europe. It is widely accepted that gastric B-cell, low-grade mucosalassociated lymphoid tissue (MALT lymphoma is caused by specific host-bacterial interactions that occur during Helicobacter pylori infection. This review examines recent findings on the origins, diagnosis, treatment, and follow-up of gastric MALT lymphomas. Clinical and endoscopic findings at diagnosis vary widely. In a substantial number of cases, the patient presents only vague dyspeptic symptoms or poorly defined abdominal pain with no macroscopic lesions on the gastric mucosa. Review of data from 32 trials in which a total of 1,387 MALT-lymphoma patients of the stomach were treated solely with H. pylori eradication revealed high remission rates when the disease is treated early (stage I-II1. Neoplasia confined to the submucosa, antral localization of tumors, and negativity for the API2-MALT1 translocation were associated with a high probability of remission following H. pylori eradication. When the latter approach is not sufficient, radiotherapy, chemotherapy and, in selected cases, surgery are associated with high success rates; data on the efficacy of monoclonal antibody therapy (rituximab are still limited. Five-year survival rates are higher than 90%. Patients whose tumors have been eliminated require close, long-term endoscopic follow-up since recurrence has been reported in some cases. Broader clinical follow-up is also advisable because the incidence of other solid tumors and of cardiovascular events is reportedly increased in these patients.

  4. Smallpox: emergence, global spread, and eradication.

    Science.gov (United States)

    Fenner, F

    1993-01-01

    Speculatively, it is suggested that variola virus, the cause of smallpox, evolved from an orthopoxvirus of animals of the central African rain forests (possibly now represented by Tatera poxvirus), some thousands of years ago, and first became established as a virus specific for human beings in the dense populations of the Nile valley perhaps five thousand years ago. By the end of the first millennium of the Christian era, it had spread to all the densely populated parts of the Eurasian continent and along the Mediterranean fringe of north Africa. It became established in Europe during the times of the Crusades. The great voyages of European colonization carried smallpox to the Americas and to Africa south of the Sahara. Transported across the Atlantic by Europeans and their African slaves, it played a major role in the conquest of Mexico and Peru and the European settlement of north America. Variolation, an effective preventive inoculation, was devised as early as the tenth century. In 1798 this practice was supplanted by Jenner's cowpox vaccine. In 1967, when the disease was still endemic in 31 countries and caused ten to fifteen million cases and about two million deaths annually, the World Health Organization embarked on a programme that was to see the disease eradicated globally just over ten years later, and the world was formally declared to be free of smallpox in May 1980. Smallpox is unique--a specifically human disease that emerged from some animal reservoir, spread to become a worldwide, severe and almost universal affliction, and finally underwent the reverse process to emergence, namely global eradication.

  5. Partial purification of chlorophyll degrading enzymes from cavendish banana (Musa Cavendishi)

    National Research Council Canada - National Science Library

    Janave, Machhindra T; Sharma, Arun

    2004-01-01

    ...), due to incomplete degradation of chlorophyll (Chl). Earlier, evidence for the existence of two distinct degradative pathways--chlorophyllase and chlorophyll oxidase pathways in these bananas was provided...

  6. Endgame for polio eradication? Options for overcoming social and political factors in the progress to eradicating polio.

    Science.gov (United States)

    Ganapathiraju, Pavan V; Morssink, Christiaan B; Plumb, James

    2015-01-01

    In 1988, the Global Polio Eradication Initiative (GPEI) was launched with the goal of eradicating polio by the year 2000. After 25 years, several dynamics still challenge this large public health campaign with new cases of polio being reported annually. We examine the roots of this initiative to eradicate polio, its scope, the successes and setbacks during the last 25 years and reflect on the current state of affairs. We examine the social and political factors that are barriers to polio eradication. Options are discussed for solving the current impasse of polio eradication: using force, respecting individual freedoms and gaining support from those vulnerable to fundamentalist 'propaganda'. The travails of the GPEI indicate the need for expanding the Convention on the Rights of the Child to address situations of war and civic strife. Such a cultural and structural reference will provide the basis for global stakeholders to engage belligerent local actors whose local political conflicts are barriers to the eradication of polio. Disregard for these actors will result in stagnation of polio eradication policy, delaying eradication beyond 2018.

  7. Early Attempts to Eradicate Helicobacter pylori after Endoscopic Resection of Gastric Neoplasm Significantly Improve Eradication Success Rates

    Science.gov (United States)

    Huh, Cheal Wung; Youn, Young Hoon; Jung, Da Hyun; Park, Jae Jun; Kim, Jie-Hyun; Park, Hyojin

    2016-01-01

    Purpose After endoscopic resection (ER) of gastric tumors, eradication of Helicobacter pylori (H. pylori) infection is advised to reduce metachronous recurrence. Optimal timing of such therapy (yet to be established) was investigated herein, examining early active and late scarring stages of post-ER iatrogenic ulcers. Materials and Methods Analysis included 514 patients who received proton-pump inhibitor (PPI)-based triple therapy for H. pylori eradication after ER for gastric neoplasms between January 2008 and June 2015. Clinicopathologic characteristics, particularly the timing of triple therapy, were used to compare eradication rates, assigning patients to early- (≤2 weeks), intermediate- (2–8 weeks), and late-phase (≥8 weeks) treatment groups. Results H. pylori eradication rates differed significantly by timing of triple therapy after ER (early, 90.0%; intermediate, 76.2%, late, 72.4%; p ulcer, and duration of therapeutic regimen. Early initiation of H. pylori eradication was also identified as a significant independent predictor of eradication success in multivariate analysis (Odds ratio = 3.67, 95% CI 2.18–6.16; p <.001). Conclusion In patients undergoing ER of gastric tumors, early post-ER attempts at eradication of H. pylori offer the best chance of eradication success. PMID:27588679

  8. Archipelago-wide island restoration in the Galapagos Islands: reducing costs of invasive mammal eradication programs and reinvasion risk.

    Directory of Open Access Journals (Sweden)

    Victor Carrion

    Full Text Available Invasive alien mammals are the major driver of biodiversity loss and ecosystem degradation on islands. Over the past three decades, invasive mammal eradication from islands has become one of society's most powerful tools for preventing extinction of insular endemics and restoring insular ecosystems. As practitioners tackle larger islands for restoration, three factors will heavily influence success and outcomes: the degree of local support, the ability to mitigate for non-target impacts, and the ability to eradicate non-native species more cost-effectively. Investments in removing invasive species, however, must be weighed against the risk of reintroduction. One way to reduce reintroduction risks is to eradicate the target invasive species from an entire archipelago, and thus eliminate readily available sources. We illustrate the costs and benefits of this approach with the efforts to remove invasive goats from the Galápagos Islands. Project Isabela, the world's largest island restoration effort to date, removed >140,000 goats from >500,000 ha for a cost of US$10.5 million. Leveraging the capacity built during Project Isabela, and given that goat reintroductions have been common over the past decade, we implemented an archipelago-wide goat eradication strategy. Feral goats remain on three islands in the archipelago, and removal efforts are underway. Efforts on the Galápagos Islands demonstrate that for some species, island size is no longer the limiting factor with respect to eradication. Rather, bureaucratic processes, financing, political will, and stakeholder approval appear to be the new challenges. Eradication efforts have delivered a suite of biodiversity benefits that are in the process of revealing themselves. The costs of rectifying intentional reintroductions are high in terms of financial and human resources. Reducing the archipelago-wide goat density to low levels is a technical approach to reducing reintroduction risk in the short

  9. Endo-β-N-acetylglucosamidases (ENGases) in the fungus Trichoderma atroviride: possible involvement of the filamentous fungi-specific cytosolic ENGase in the ERAD process.

    Science.gov (United States)

    Tzelepis, Georgios; Hosomi, Akira; Hossain, Tanim Jabid; Hirayama, Hiroto; Dubey, Mukesh; Jensen, Dan Funck; Suzuki, Tadashi; Karlsson, Magnus

    2014-06-27

    N-Glycosylation is an important post-translational modification of proteins, which mainly occurs in the endoplasmic reticulum (ER). Glycoproteins that are unable to fold properly are exported to the cytosol for degradation by a cellular system called ER-associated degradation (ERAD). Once misfolded glycoproteins are exported to the cytosol, they are subjected to deglycosylation by peptide:N-glycanase (PNGase) to facilitate the efficient degradation of misfolded proteins by the proteasome. Interestingly, the ortholog of PNGase in some filamentous fungi was found to be an inactive deglycosylating enzyme. On the other hand, it has been shown that in filamentous fungi genomes, usually two different fungi-specific endo-β-N-acetylglucosamidases (ENGases) can be found; one is predicted to be localized in the cytosol and the other to have a signal sequence, while the functional importance of these enzymes remains to be clarified. In this study the ENGases of the filamentous fungus Trichoderma atroviride was characterized. By heterologous expression of the ENGases Eng18A and Eng18B in Saccharomyces cerevisiae, it was found that both ENGases are active deglycosylating enzymes. Interestingly, only Eng18B was able to enhance the efficient degradation of the RTL protein, a PNGase-dependent ERAD substrate, implying the involvement of this enzyme in the ERAD process. These results indicate that T. atroviride Eng18B may deglycosylate misfolded glycoproteins, substituting the function of the cytoplasmic PNGase in the ERAD process.

  10. NOXA, a sensor of proteasome integrity, is degraded by 26S proteasomes by an ubiquitin-independent pathway that is blocked by MCL-1

    OpenAIRE

    2012-01-01

    Ubiquitin (Ub)-mediated proteasome-dependent proteolysis is critical in regulating multiple biological processes including apoptosis. We show that the unstructured BH3-only protein, NOXA, is degraded by an Ub-independent mechanism requiring 19S regulatory particle (RP) subunits of the 26S proteasome, highlighting the possibility that other unstructured proteins reported to be degraded by 20S proteasomes in vitro may be bona fide 26S proteasome substrates in vivo. A lysine-less NOXA (NOXA-LL) ...

  11. Managing breaches of containment and eradication of invasive plant populations.

    Science.gov (United States)

    Fletcher, Cameron S; Westcott, David A; Murphy, Helen T; Grice, Anthony C; Clarkson, John R

    2015-02-01

    Containment can be a viable strategy for managing invasive plants, but it is not always cheaper than eradication. In many cases, converting a failed eradication programme to a containment programme is not economically justified. Despite this, many contemporary invasive plant management strategies invoke containment as a fallback for failed eradication, often without detailing how containment would be implemented.We demonstrate a generalized analysis of the costs of eradication and containment, applicable to any plant invasion for which infestation size, dispersal distance, seed bank lifetime and the economic discount rate are specified. We estimate the costs of adapting eradication and containment in response to six types of breach and calculate under what conditions containment may provide a valid fallback to a breached eradication programme.We provide simple, general formulae and plots that can be applied to any invasion and show that containment will be cheaper than eradication only when the size of the occupied zone exceeds a multiple of the dispersal distance determined by seed bank longevity and the discount rate. Containment becomes proportionally cheaper than eradication for invaders with smaller dispersal distances, longer lived seed banks, or for larger discount rates.Both containment and eradication programmes are at risk of breach. Containment is less exposed to risk from reproduction in the 'occupied zone' and three types of breach that lead to a larger 'occupied zone', but more exposed to one type of breach that leads to a larger 'buffer zone'.For a well-specified eradication programme, only the three types of breach leading to reproduction in or just outside the buffer zone can justify falling back to containment, and only if the expected costs of eradication and containment were comparable before the breach.Synthesis and applications. Weed management plans must apply a consistent definition of containment and provide sufficient implementation detail

  12. Tyrosinase degradation is prevented when EDEM1 lacks the intrinsically disordered region.

    Directory of Open Access Journals (Sweden)

    Marioara B Marin

    Full Text Available EDEM1 is a mannosidase-like protein that recruits misfolded glycoproteins from the calnexin/calreticulin folding cycle to downstream endoplasmic reticulum associated degradation (ERAD pathway. Here, we investigate the role of EDEM1 in the processing of tyrosinase, a tumour antigen overexpressed in melanoma cells. First, we analyzed and modeled EDEM1 major domains. The homology model raised on the crystal structures of human and Saccharomyces cerevisiae ER class I α1,2-mannosidases reveals that the major mannosidase domain located between aminoacids 121-598 fits with high accuracy. We have further identified an N-terminal region located between aminoacids 40-119, predicted to be intrinsically disordered (ID and susceptible to adopt multiple conformations, hence facilitating protein-protein interactions. To investigate these two domains we have constructed an EDEM1 deletion mutant lacking the ID region and a triple mutant disrupting the glycan-binding domain and analyzed their association with tyrosinase. Tyrosinase is a glycoprotein partly degraded endogenously by ERAD and the ubiquitin proteasomal system. We found that the degradation of wild type and misfolded tyrosinase was enhanced when EDEM1 was overexpressed. Glycosylated and non-glycosylated mutants co-immunoprecipitated with EDEM1 even in the absence of its intact mannosidase-like domain, but not when the ID region was deleted. In contrast, calnexin and SEL 1L associated with the deletion mutant. Our data suggest that the ID region identified in the N-terminal end of EDEM1 is involved in the binding of glycosylated and non-glycosylated misfolded proteins. Accelerating tyrosinase degradation by EDEM1 overexpression may lead to an efficient antigen presentation and enhanced elimination of melanoma cells.

  13. 计算机重构石油烃降解的微生物代谢途径%Computational Reconstruction of Microbial Pathways for Degradation of Petroleum Hydrocarbons

    Institute of Scientific and Technical Information of China (English)

    王东; 何涛; 邵卫东; 汪莉; 王玉民

    2012-01-01

    目的:用计算机重构石油烃降解通路,为石油污染的生物修复提供理论依据.方法:利用KEGG反应、化合物数据提取反应等式,过滤掉所有反应中的通用化合物及小分子化合物并构建反应矩阵,然后利用广度优先搜索算法在反应矩阵中搜索降解石油烃的代谢途径.结果:计算机分别重构了256 132条链烷烃降解途径和44条环己烷降解途径,以酿酒酵母作为降解石油烃的基因工程菌为例,通过限制改构菌整合的关键酶数目,分别得到了213条不需要转入关键酶的链烷烃降解通路和6条以氧化还原酶、松柏醇脱氢酶或环己醇脱氢酶和环己酮单氧酶为关键酶的环己烷降解通路,并构建相应的降解网络图,标注每个反应的酶.结论:应用计算机重构了2种石油烃降解途径,可为利用微生物对石油污染进行生物修复提供理论依据.%Objective: Metabolic pathways for degradation of petroleum hydrocarbons were reconstructed by computational skills to provide theoretical basis for the bioremediation of oil polution. Methods: At first, the reaction equations were extracted from the KEGC reaction database and the compound database. And then current metabolites and micromolecule compounds in all the reactions were filtered out. Finally, the reaction matrix was constructed to search metabolic pathways for degrading petroleum hydrocarbons by the breadth first search approach. Results: 256 132 pathways for degrading alkanes and 44 pathways for degrading cyclohexane were reconstructed by computational skills. Taking Saccharomyces cerevisiae as the genetic engineering bacteria, we picked out 219 pathways by limiting the number of pivotal enzymes to construct the metabolic network, including 213 pathways without key enzymes and 6 pathways with oxidoreductases, coniferyl alcohol dehydrogenase or cyclohexanol dehydroge-nase and cyclohexanone monooxygenase as key enzymes. Catalytic enzymes of every reaction

  14. Quinolone-containing therapies in the eradication of Helicobacter pylori.

    Science.gov (United States)

    Chuah, Seng-Kee; Tai, Wei-Chen; Lee, Chen-Hsiang; Liang, Chih-Ming; Hu, Tsung-Hui

    2014-01-01

    Fluoroquinolones, especially levofloxacin, are used in the eradication of Helicobacter pylori worldwide. Many consensus guidelines recommend that the second-line rescue therapy for H. pylori eradication consists of a proton pump inhibitor, a quinolone, and amoxicillin as an option. Unfortunately, quinolone is well associated with a risk of developing bacterial resistance. In this paper, we review quinolone-containing H. pylori eradication regimens and the challenges that influence the efficacy of eradication. It is generally suggested that the use of levofloxacin should be confined to "rescue" therapy only, in order to avoid a further rapid increase in the resistance of H. pylori to quinolone. The impact of quinolone-containing H. pylori eradication regimens on public health issues such as tuberculosis treatment must always be taken into account. Exposure to quinolone is relevant to delays in diagnosing tuberculosis and the development of drug resistance. Extending the duration of treatment to 14 days improves eradication rates by >90%. Tailored therapy to detect fluoroquinolone-resistant strains can be done by culture-based and molecular methods to provide better eradication rates. Molecular methods are achieved by using a real-time polymerase chain reaction to detect the presence of a gyrA mutation, which is predictive of treatment failure with quinolones-containing triple therapy.

  15. The Opportunity To Eradicate Peste des Petits Ruminants.

    Science.gov (United States)

    Mariner, Jeffrey C; Jones, Bryony A; Rich, Karl M; Thevasagayam, Samuel; Anderson, John; Jeggo, Martyn; Cai, Yi; Peters, Andrew R; Roeder, Peter L

    2016-05-01

    Peste des petits ruminants (PPR) is a highly infectious disease of sheep and goats that is caused by PPR virus, a member of the genus Morbillivirus that includes the viruses that cause rinderpest (RP) in cattle. RP was the first animal disease to be globally eradicated in 2011 and is only the second disease, after smallpox, to have ever been eradicated. PPR is one of the principal constraints to small ruminant production in Africa, Asia, and the Middle East. The epidemiology of PPR and RP as well as the technologies available for their diagnosis and control are similar. The conditions that favored the eradication of RP are also largely present for PPR. In this work, we outline the evolving strategy for eradication in light of current opportunities and challenges, as well as the lessons from other eradication programs in animal and human health. The global PPR situation and technology for its control are summarized. A strategy based on the lessons from previous eradication efforts that integrate epidemiology, social science, and economics as tools to target and motivate vaccination is summarized. Major aspects of the cost and benefit-cost analysis of the indicated program are presented. The overall undiscounted cost of eradication was estimated as $3.1 billion, and the benefit-cost ratio for the most likely scenario was estimated at 33.8. We close with a discussion of the possible next steps. Copyright © 2016 by The American Association of Immunologists, Inc.

  16. Pylera for the eradication of Helicobacter pylori infection.

    LENUS (Irish Health Repository)

    Saleem, Aamir

    2012-02-01

    An ideal antibiotic regimen for Helicobacter pylori should achieve eradication rates of approximately 90%. Current 7-day triple therapy is successful in about two-thirds of patients. A novel treatment is required to achieve higher eradication with minimal induction of bacterial resistance. The aim of this article is to evaluate the safety and efficacy of a single triple capsule (Pylera) containing bismuth, metronidazole and tetracycline, given with omeprazole for the eradication of H. pylori infection. Extensive literature searches were conducted using PubMed data from 1982 to 2007. This search included headings of H. pylori, bismuth and eradication therapy. The triple capsule Pylera, when given with omeprazole, achieved eradication rates ranging between 84 and 97%. Eradication rates were similar for clarithromycin- and metronidazole-resistant strains. Eradication rates with an omeprazole, bismuth, metronidazole and tetracycline regimen appeared comparable for metronidazole-resistant and -sensitive strains. This effect is not seen with the use of triple therapy in cases of clarithromycin resistance. Clinical trials did not report any serious side effects from bismuth-based regimens and compliance was similar to standard triple therapy. Bismuth-based triple therapy using Pylera is a simplified, effective and well-tolerated regimen achieving cure rates of above 90%.

  17. Six challenges in the eradication of infectious diseases

    Directory of Open Access Journals (Sweden)

    Petra Klepac

    2015-03-01

    Full Text Available Eradication and elimination are increasingly a part of the global health agenda. Once control measures have driven infection to low levels, the ecology of disease may change posing challenges for eradication efforts. These challenges vary from identifying pockets of susceptibles, improving monitoring during and after the endgame, to quantifying the economics of disease eradication versus sustained control, all of which are shaped and influenced by processes of loss of immunity, susceptible build-up, emergence of resistance, population heterogeneities and non-compliance with control measures. Here we discuss how modelling can be used to address these challenges.

  18. The polio eradication campaign: time to shift the goal.

    Science.gov (United States)

    Baron, Emmanuel; Magone, Claire

    2014-03-01

    The social rejection of the polio eradication campaign in endemic countries challenges an assumption underlying the goal itself: the full compliance of an entire population to a public health programme. The polio campaign, which has been an extraordinary public health enterprise, is at risk of becoming irremediably unpopular if the eradication goal is pursued at all costs. The Global Polio Eradication Initiative (GPEI) should not be driven by the fear of failure, because the greatest benefit of the polio campaign is that it has demonstrated how simple, community-wide actions can contribute to a dramatic decrease in the incidence of a disease.

  19. Peste des petits ruminants: a suitable candidate for eradication?

    Science.gov (United States)

    Baron, M D; Parida, S; Oura, C A L

    2011-07-02

    This year will see the final announcement, accompanied by much justifiable celebration, of the eradication from the wild of rinderpest, the 'cattle plague' that has been with us for so many centuries. The only known rinderpest virus (RPV) remaining is in a relatively small number of laboratories around the world, and in the stockpiles of vaccine held on a precautionary basis. As we mark this achievement, only the second virus ever eradicated through human intervention, it seems a good time to look at rinderpest's less famous cousin, peste des petits ruminants ('the plague of small ruminants') and assess if it should, and could, also be targeted for global eradication.

  20. Age-dependent eradication of Helicobacter pylori in Japanese patients

    Institute of Scientific and Technical Information of China (English)

    Satoshi; Mamori; Akihiro; Higashida; Fumiaki; Kawara; Katsuhiro; Ohnishi; Akihiko; Takeda; Eri; Senda; Cho; Ashida; Hajime; Yamada

    2010-01-01

    AIM:To determine the general risk factors affecting the failure rate of first-line eradication therapy in Japanese patients with Helicobacter pylori(H.pylori)infection.METHODS:The present study enrolled 253 patients who had an H.pylori infection,underwent gastroendoscopy,and were treated with H.pylori eradication therapy.Eradication therapy consisted of 30 mg lansoprazole plus 750 mg amoxicillin and 400 mg clarithromycin twice daily for 7 d.All of the patients underwent a 13 C urea breath test at least 1 mo...

  1. Roles of horizontal gene transfer and gene integration in evolution of 1,3-dichloropropene- and 1,2-dibromoethane-degradative pathways

    NARCIS (Netherlands)

    Poelarends, GJ; Kulakov, LA; Larkin, MJ; Vlieg, JETV; Janssen, DB; Kulakov, Leonid A.; Larkin, Michael J.; Hylckama Vlieg, Johan E.T. van

    2000-01-01

    The haloalkane-degrading bacteria Rhodococcus rhodochrous NCIMB13064, Pseudomonas pavonaceae 170, and Mycobacterium sp. strain GP1 share a highly conserved haloalkane dehalogenase gene (dhaA). Here, we describe the extent of the conserved dhaA segments in these three phylogenetically distinct bacter

  2. NOXA, a sensor of proteasome integrity, is degraded by 26S proteasomes by an ubiquitin-independent pathway that is blocked by MCL-1.

    Science.gov (United States)

    Craxton, A; Butterworth, M; Harper, N; Fairall, L; Schwabe, J; Ciechanover, A; Cohen, G M

    2012-09-01

    Ubiquitin (Ub)-mediated proteasome-dependent proteolysis is critical in regulating multiple biological processes including apoptosis. We show that the unstructured BH3-only protein, NOXA, is degraded by an Ub-independent mechanism requiring 19S regulatory particle (RP) subunits of the 26S proteasome, highlighting the possibility that other unstructured proteins reported to be degraded by 20S proteasomes in vitro may be bona fide 26S proteasome substrates in vivo. A lysine-less NOXA (NOXA-LL) mutant, which is not ubiquitinated, is degraded at a similar rate to wild-type NOXA. Myeloid cell leukemia 1, but not other anti-apoptotic BCL-2 family proteins, stabilizes NOXA by interaction with the NOXA BH3 domain. Depletion of 19S RP subunits, but not alternate proteasome activator REG subunits, increases NOXA half-life in vivo. A NOXA-LL mutant, which is not ubiquitinated, also requires an intact 26S proteasome for degradation. Depletion of the 19S non-ATPase subunit, PSMD1 induces NOXA-dependent apoptosis. Thus, disruption of 26S proteasome function by various mechanisms triggers the rapid accumulation of NOXA and subsequent cell death strongly implicating NOXA as a sensor of 26S proteasome integrity.

  3. Mid-Columbia - Yellow-flag Iris Eradication 2014

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — The project as described was to attempt to eradicate yellow-flag iris from Toppenish, McNary and Columbia National Wildlife Refuges using chemical and, where...

  4. Mid-Columbia - Eradication of Yellow-flag Iris 2013

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — The project as described was to attempt to eradicate yellow-flag iris from Toppenish, McNary and Columbia National Wildlife Refuges using chemical and, where...

  5. Control and eradication of endemic infectious diseases in cattle

    DEFF Research Database (Denmark)

    Houe, Hans; Nielsen, Liza Rosenbaum; Nielsen, Søren Saxmose

    exist? Who should be involved and informed, and how should the programme be organised? Where should the programme be implemented? What measures should be used to monitor progress? When can we conclude that control and eradication have been achieved? The key elements are illustrated primarily using three......"Control and eradication of endemic infectious diseases in cattle" provides the key elements that should be addressed in the establishment of bovine disease control and eradication programmes. The book aims to reach a broad group of readers, including: students; professionals in veterinary practice......, industry and governmental institutions; researchers; and others involved in control and eradication of endemic diseases in livestock. Key elements range from socioeconomic aspects such as motivation; veterinary science (including assessment of biosecurity and establishment of test...

  6. Attempted eradication of Porphyrio porphyrio Linnaeus in the Florida Everglades

    Directory of Open Access Journals (Sweden)

    Dave EGGEMAN

    2011-01-01

    Full Text Available Porphyrio porphyrio (Fulica porphyrio Linnaeus was reported to the South Florida Water Management District in a Water Conservation Area and in constructed wetlands in the Everglades in 2006. A rapid assessment, including casual observations and surveys of land managers, indicated a limited number of P. porphyrio (~300 birds was present, and an eradication attempt was initiated. From 2006 – 2008, more than 3100 P. porphyrio were killed by shotgun from airboats during 73 hunts, suggesting the initial population assessment was severely underestimated. After removing nearly 1500 P. porphyrio in 2008, we concluded that eradication was not possible. Failure of this eradication attempt is attributed to P. porphyrio’s affinity with dense emergent vegetation, which greatly limited shooting effectiveness. Further, the failed eradication underscores the importance of a reporting network to improve early detection and the chance to eliminate naturalized or feral populations of non‐native species.

  7. Acute ER stress regulates amyloid precursor protein processing through ubiquitin-dependent degradation.

    Science.gov (United States)

    Jung, Eun Sun; Hong, HyunSeok; Kim, Chaeyoung; Mook-Jung, Inhee

    2015-03-05

    Beta-amyloid (Aβ), a major pathological hallmark of Alzheimer's disease (AD), is derived from amyloid precursor protein (APP) through sequential cleavage by β-secretase and γ-secretase enzymes. APP is an integral membrane protein, and plays a key role in the pathogenesis of AD; however, the biological function of APP is still unclear. The present study shows that APP is rapidly degraded by the ubiquitin-proteasome system (UPS) in the CHO cell line in response to endoplasmic reticulum (ER) stress, such as calcium ionophore, A23187, induced calcium influx. Increased levels of intracellular calcium by A23187 induces polyubiquitination of APP, causing its degradation. A23187-induced reduction of APP is prevented by the proteasome inhibitor MG132. Furthermore, an increase in levels of the endoplasmic reticulum-associated degradation (ERAD) marker, E3 ubiquitin ligase HRD1, proteasome activity, and decreased levels of the deubiquitinating enzyme USP25 were observed during ER stress. In addition, we found that APP interacts with USP25. These findings suggest that acute ER stress induces degradation of full-length APP via the ubiquitin-proteasome proteolytic pathway.

  8. The Veron Community Scabies Education and Eradication Program

    OpenAIRE

    White, Jeremy Jason

    2009-01-01

    Skin infections by the ectoparasitic mite Sarcoptes scabiei are a preventable source of morbidity worldwide. While scabies affects all socioeconomic sectors, it is especially prominent in the developing world where crowding, poor hygiene, and limited access to basic health care are commonplace. Mass eradication efforts of this parasite have historically been hampered by delivery and compliance issues surrounding topical standards of care. There have been advances in eradication over the las...

  9. African swine fever virus eradication in Africa.

    Science.gov (United States)

    Penrith, Mary-Louise; Vosloo, Wilna; Jori, Ferran; Bastos, Armanda D S

    2013-04-01

    African swine fever was reported in domestic pigs in 26 African countries during the period 2009-2011. The virus exists in an ancient sylvatic cycle between warthogs (Phacochoerus africanus) and argasid ticks of the Ornithodoros moubata complex in many of the countries reporting outbreaks and in two further countries in the region. Eradication of the virus from the countries in eastern and southern Africa where the classic sylvatic cycle occurs is clearly not an option. However, the virus has become endemic in domestic pigs in 20 countries and the great majority of outbreaks in recent decades, even in some countries where the sylvatic cycle occurs, have been associated with movement of infected pigs and pig meat. Pig production and marketing and ASF control in Africa have been examined in order to identify risk factors for the maintenance and spread of ASF. These include large pig populations, traditional free-range husbandry systems, lack of biosecurity in semi-intensive and intensive husbandry systems, lack of organisation in both pig production and pig marketing that results in lack of incentives for investment in pig farming, and ineffective management of ASF. Most of these factors are linked to poverty, yet pigs are recognised as a livestock species that can be used to improve livelihoods and contribute significantly to food security. The changes needed and how they might be implemented in order to reduce the risk of ASF to pig producers in Africa and to the rest of the world are explored. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. Leprosy - evolution of the path to eradication

    Science.gov (United States)

    Dogra, Sunil; Narang, Tarun; Kumar, Bhushan

    2013-01-01

    Leprosy is among the world's oldest and most dreaded diseases and it has been synonymous with stigma and discrimination due to the hideous deformities it produced, mystery around its aetiology and transmission and lack of any effective remedy till recently. Leprosy control started with the use of chaulmoogra oil and for the last three decades, multi drug therapy (MDT) has been our main tool against leprosy. In the last two decades, the reported global prevalence of active leprosy infection has dropped by almost 90 per cent by the combined efforts of the World Health Organization (WHO), local governments, health professionals, and non-governmental organizations (NGOs), however, a parallel drop in the incidence or new case detection rate (NCDR) has not occurred. From 1994 through 2011, more than 100,000 new cases are being detected annually, of whom maximum case load is from India. There is need for research on tools for early diagnosis, short and effective treatment, and prevention of deformities and disabilities. Evaluating the role of immunotherapy and immunoprophylaxis will also lead us to better understanding of their mode of action. Further molecular analysis of Mycobacterium leprae genome may provide the requisite basis for all this. The current reality is that there is a need to sustain and provide quality leprosy services to all persons through general health services, including good referral system. All these provisions in the integrated health care approach will go a long way in further reducing the stigma. Efforts need to be made to reduce deformity through early detection, self care, physiotherapy and reconstructive surgery and developing sound surveillance systems. With all the remarkable achievements in the fight against leprosy, the stage is now set for the final assault. It is hoped that with the efforts of all the stake holders and strong political will, the disease will be eradicated in the near future. PMID:23481049

  11. After Beijing: emphasis on poverty eradication.

    Science.gov (United States)

    1996-01-01

    In March 1996, during its first meeting since the Fourth World Conference on Women, the UN Commission on the Status of Women (CSW), called for a gender perspective to be integrated into policies and programs dealing with poverty, child and dependent care, and the media. Three expert panels examined each of these areas through a format which encouraged dialogue and led to the adoption of 17 resolutions, decisions, and agreed conclusions as well as a recommendation that the UN adopt a multi-year work program for the CSW to allow it to review progress in elimination of the 12 main obstacles to women's advancement identified at Beijing. Among the resolutions adopted by the CSW were calls to 1) take a broad and integrated approach to poverty eradication, 2) enhance women's empowerment and autonomy, 3) promote equity and equality in the public domain, 4) promote women's employment, 5) give women social and economic protection when they are unable to work, 6) counteract negative images of women and sex-stereotyping in the media, 7) reduce the representation of violence against women in the media, 8) strengthen the role of women in global communications, 9) encourage the participation of men in child and dependent care, and 10) recognize women's double burden of work. The CSW also agreed to pursue further discussions about drafting an optional protocol to the 1979 Convention on the Elimination of All Forms of Discrimination Against Women. Among its other actions, the CSW called for mechanisms to protect the rights of women migrant workers, to protect women and children during armed conflicts, to include gender-based human rights violations in UN activities, and to address the root factors which lead to social ills such as trafficking in women and girls. In addition, the CSW submitted a draft resolution demanding that Israel protect the rights of Palestinian women and their families.

  12. The final stages of the global eradication of poliomyelitis.

    Science.gov (United States)

    Grassly, Nicholas C

    2013-08-05

    The global incidence of poliomyelitis has dropped by more than 99 per cent since the governments of the world committed to eradication in 1988. One of the three serotypes of wild poliovirus has been eradicated and the remaining two serotypes are limited to just a small number of endemic regions. However, the Global Polio Eradication Initiative (GPEI) has faced a number of challenges in eradicating the last 1 per cent of wild-virus transmission. The polio endgame has also been complicated by the recognition that vaccination with the oral poliovirus vaccine (OPV) must eventually cease because of the risk of outbreaks of vaccine-derived polioviruses. I describe the major challenges to wild poliovirus eradication, focusing on the poor immunogenicity of OPV in lower-income countries, the inherent limitations to the sensitivity and specificity of surveillance, the international spread of poliovirus and resulting outbreaks, and the potential significance of waning intestinal immunity induced by OPV. I then focus on the challenges to eradicating all polioviruses, the problem of vaccine-derived polioviruses and the risk of wild-type or vaccine-derived poliovirus re-emergence after the cessation of oral vaccination. I document the role of research in the GPEI's response to these challenges and ultimately the feasibility of achieving a world without poliomyelitis.

  13. Progress toward global eradication of dracunculiasis, January 2008-June 2009.

    Science.gov (United States)

    2009-10-16

    Dracunculiasis is a parasitic infection caused by Dracunculus medinensis. Persons become infected by drinking water from stagnant sources (e.g., ponds) contaminated by copepods (water fleas) that contain immature forms of the parasite. In 1986, the World Health Assembly (WHA) called for the eradication of dracunculiasis (Guinea worm disease) at a time when an estimated 3.5 million cases occurred annually in 20 countries in Africa and Asia and 120 million persons were at risk for the disease. Because of slow mobilization in countries with endemic disease, the global dracunculiasis eradication program did not meet the 1995 target date for eradicating dracunculiasis set by WHA in 1991. In 2004, WHA established a new target date of 2009 ; despite considerable progress toward global eradication, that target date also will not be met. This report updates continued progress toward global eradication of dracunculiasis since January 2008. At the end of December 2008, dracunculiasis was endemic in six countries (Ethiopia, Ghana, Mali, Niger, Nigeria, and Sudan). The number of indigenous cases of dracunculiasis had decreased 52%, from 9,585 in 2007 to 4,619 in 2008. Of the 1,446 cases that occurred during January-June 2009, 1,413 (98%) were reported from Sudan and Ghana. Currently, insecurity (e.g., sporadic violence or civil unrest) in areas of Sudan and Mali where dracunculiasis is endemic poses the greatest threat to the success of the global dracunculiasis eradication program.

  14. Mathematical Modeling of Programmatic Requirements for Yaws Eradication

    Science.gov (United States)

    Mitjà, Oriol; Fitzpatrick, Christopher; Asiedu, Kingsley; Solomon, Anthony W.; Mabey, David C.W.; Funk, Sebastian

    2017-01-01

    Yaws is targeted for eradication by 2020. The mainstay of the eradication strategy is mass treatment followed by case finding. Modeling has been used to inform programmatic requirements for other neglected tropical diseases and could provide insights into yaws eradication. We developed a model of yaws transmission varying the coverage and number of rounds of treatment. The estimated number of cases arising from an index case (basic reproduction number [R0]) ranged from 1.08 to 3.32. To have 80% probability of achieving eradication, 8 rounds of treatment with 80% coverage were required at low estimates of R0 (1.45). This requirement increased to 95% at high estimates of R0 (2.47). Extending the treatment interval to 12 months increased requirements at all estimates of R0. At high estimates of R0 with 12 monthly rounds of treatment, no combination of variables achieved eradication. Models should be used to guide the scale-up of yaws eradication. PMID:27983500

  15. Successes and shortcomings of polio eradication: a transmission modeling analysis.

    Science.gov (United States)

    Mayer, Bryan T; Eisenberg, Joseph N S; Henry, Christopher J; Gomes, M Gabriela M; Ionides, Edward L; Koopman, James S

    2013-06-01

    Polio eradication is on the cusp of success, with only a few regions still maintaining transmission. Improving our understanding of why some regions have been successful and others have not will help with both global eradication of polio and development of more effective vaccination strategies for other pathogens. To examine the past 25 years of eradication efforts, we constructed a transmission model for wild poliovirus that incorporates waning immunity (which affects both infection risk and transmissibility of any resulting infection), age-mediated vaccination rates, and transmission of oral polio vaccine. The model produces results consistent with the 4 country categories defined by the Global Polio Eradication Program: elimination with no subsequent outbreaks; elimination with subsequent transient outbreaks; elimination with subsequent outbreaks and transmission detected for more than 12 months; and endemic polio transmission. Analysis of waning immunity rates and oral polio vaccine transmissibility reveals that higher waning immunity rates make eradication more difficult because of increasing numbers of infectious adults, and that higher oral polio vaccine transmission rates make eradication easier as adults become reimmunized. Given these dynamic properties, attention should be given to intervention strategies that complement childhood vaccination. For example, improvement in sanitation can reduce the reproduction number in problematic regions, and adult vaccination can lower adult transmission.

  16. Characterization, Degradation, and Reaction Pathways of Indoor Toluene over Visible-light-driven S, Zn Co-doped TiO2

    Science.gov (United States)

    Chu, H.; Lin, Y. H.; Lin, C. Y.

    2017-01-01

    Sulfur and Zinc co-doped TiO2 prepared by a sol-gel method to degrade toluene under a fluorescent lamp was investigated. The results indicate that S,Zn co-doped TiO2 photocatalysts are mainly nano-size with an anatase phase structure. The degradation reactions of toluene were performed under various operation conditions. The results show that the toluene conversion increases with increasing toluene concentration and decreasing relative humidity. Based on the results of activity test, S0.05Zn0.001/TiO2 was chosen for further studies. The main oxidation products of toluene photodegradation are CO2, H2O, benzyl alcohol, acetone, butadiene and acetic acid. Two possible mechanisms have been developed for photodegradation of toluene in a dry and a humid environment.

  17. Electrochemical treatment of penicillin, cephalosporin, and fluoroquinolone antibiotics via active chlorine: evaluation of antimicrobial activity, toxicity, matrix, and their correlation with the degradation pathways.

    Science.gov (United States)

    Serna-Galvis, Efraím A; Berrio-Perlaza, Karen E; Torres-Palma, Ricardo A

    2017-09-01

    Antibiotics are pharmaceuticals widely consumed and frequently detected in environmental water, where they can induce toxic effects and development of resistant bacteria. Their structural variety makes the problem of antibiotics in natural water more complex. In this work, six highly used antibiotics (at 40 μmol L(-1)) belonging to three different classes (penicillins, cephalosporins, and fluoroquinolones) were treated using an electrochemical system with a Ti/IrO2 anode and a Zr cathode in the presence of NaCl (0.05 μmol L(-1)). The attack of electrogenerated active chlorine was found to be the main degradation route. After only 20 min of treatment, the process decreased more than 90% of the initial concentration of antibiotics, following the degradation order: fluoroquinolones > penicillins > cephalosporins. The primary interactions of the degrading agent with fluoroquinolones occurred at the cyclic amine (i.e., piperazyl ring) and the benzene ring. Meanwhile, the cephalosporins and penicillins were initially attacked on the β-lactam and sulfide groups. However, the tested penicillins presented an additional reaction on the central amide. In all cases, the transformations of antibiotics led to the antimicrobial activity decreasing. On the contrary, the toxicity level showed diverse results: increasing, decreasing, and no change, depending on the antibiotic type. In fact, due to the conservation of quinolone nucleus in the fluoroquinolone by-products, the toxicity of the treated solutions remained unchanged. With penicillins, the production of chloro-phenyl-isoxazole fragments increased the toxicity level of the resultant solution. However, the opening of β-lactam ring of cephalosporin antibiotics decreased the toxicity level of the treated solutions. Finally, the application of the treatment to synthetic hospital wastewater and seawater containing a representative antibiotic showed that the high amount of chloride ions in seawater accelerates the

  18. High quality draft genome sequence of Olivibacter sitiensis type strain (AW-6T), a diphenol degrader with genes involved in the catechol pathway

    OpenAIRE

    2014-01-01

    Olivibacter sitiensis Ntougias et al. 2007 is a member of the family Sphingobacteriaceae , phylum Bacteroidetes . Members of the genus Olivibacter are phylogenetically diverse and of significant interest. They occur in diverse habitats, such as rhizosphere and contaminated soils, viscous wastes, composts, biofilter clean-up facilities on contaminated sites and cave environments, and they are involved in the degradation of complex and toxic compounds. Here we describe the features of O. sitien...

  19. Enhancement of photocatalytic activity of Cu-doped ZnO nanorods for the degradation of an insecticide: Kinetics and reaction pathways.

    Science.gov (United States)

    Shirzad-Siboni, Mehdi; Jonidi-Jafari, Ahmad; Farzadkia, Mahdi; Esrafili, Ali; Gholami, Mitra

    2017-01-15

    The photocatalytic degradation of organophosphorus pesticide such as diazinon was investigated by Cu-doped ZnO nanorods. Cu-doped ZnO nanorods were synthesized via a facile co-precipitation method. The catalyst was characterized by XRD, FESEM, EDX, VSM, XPS, and pHzpc techniques. The effects of some operational parameters such as solution pH, Cu-doped ZnO nanorods dosage, initial diazinon concentration, oxygen and nitrogen gases, H2O2 concentration, and type of organic compounds on the degradation efficiency were discussed through the photocatalytic experiments using the Cu-doped ZnO nanorods. Neutral pH was selected as an optimal pH condition due to a photo-corrosion of ZnO in acidic and basic conditions. As the Cu-doped ZnO nanorods dosage increased up to 0.2 g/L, degradation efficiency of diazinon was continuously enhanced. Pseudo-first-order rate constant (kobs) was decreased from 0.051 to 0.0052 min(-1) and electrical energy per order (EEo) was increased from 94.12 to 923.08 (kWh/m(3)) by increasing diazinon concentration from 10 to 50 mg/L, respectively. The efficiency of the UV/Cu-doped ZnO for diazinon removal was approximately 96.97%, which was more effective than the UV/ZnO process (58.52%). Photocatalytic activity was maintained even after five successive cycles.

  20. Exogenous Melatonin Suppresses Dark-Induced Leaf Senescence by Activating the Superoxide Dismutase-Catalase Antioxidant Pathway and Down-Regulating Chlorophyll Degradation in Excised Leaves of Perennial Ryegrass (Lolium perenne L.)

    Science.gov (United States)

    Zhang, Jing; Li, Huibin; Xu, Bin; Li, Jing; Huang, Bingru

    2016-01-01

    Leaf senescence is a typical symptom in plants exposed to dark and may be regulated by plant growth regulators. The objective of this study was to determine whether exogenous application of melatonin (N-acetyl-5-methoxytryptamine) suppresses dark-induced leaf senescence and the effects of melatonin on reactive oxygen species (ROS) scavenging system and chlorophyll degradation pathway in perennial grass species. Mature perennial ryegrass (Lolium perenne L. cv. ‘Pinnacle’) leaves were excised and incubated in 3 mM 2-(N-morpholino) ethanesulfonic buffer (pH 5.8) supplemented with melatonin or water (control) and exposed to dark treatment for 8 days. Leaves treated with melatonin maintained significantly higher endogenous melatonin level, chlorophyll content, photochemical efficiency, and cell membrane stability expressed by lower electrolyte leakage and malondialdehyde (MDA) content compared to the control. Exogenous melatonin treatment also reduced the transcript level of chlorophyll degradation-associated genes and senescence marker genes (LpSAG12.1, Lph36, and Lpl69) during the dark treatment. The endogenous O2- production rate and H2O2 content were significantly lower in these excised leaves treated with melatonin compared to the water control. Exogenous melatonin treatment caused increases in enzymatic activity and transcript levels of superoxide dismutase and catalase but had no significant effects on ascorbate peroxidase, glutathione reductase, dehydroascorbate reductase, and monohydroascorbate reductase. The content of non-enzymatic antioxidants, such as ascorbate and dehydroascorbate, were decreased by melatonin treatment, while the content of glutathione and oxidized glutathione was not affected by melatonin. These results suggest that the suppression of dark-induced leaf senescence by exogenous melatonin may be associated with its roles in regulating ROS scavenging through activating the superoxide dismutase-catalase enzymatic antioxidant pathway and

  1. Exogenous melatonin suppresses dark-induced leaf senescence by activating the superoxide dismutase-catalase antioxidant pathway and down-regulating chlorophyll degradation in excised leaves of perennial ryegrass (Lolium perenne L.

    Directory of Open Access Journals (Sweden)

    Jing Zhang

    2016-10-01

    Full Text Available Leaf senescence is a typical symptom in plants exposed to dark and may be regulated by plant growth regulators. The objective of this study was to determine whether exogenous application of melatonin (N-acetyl-5-methoxytryptamine suppresses dark-induced leaf senescence and the effects of melatonin on reactive oxygen species (ROS scavenging system and chlorophyll degradation pathway in perennial grass species. Mature perennial ryegrass (Lolium perenne L. cv. ‘Pinnacle’ leaves were excised and incubated in 3 mM 2-(N-morpholino ethanesulfonic buffer (pH 5.8 supplemented with melatonin or water (control and exposed to dark treatment for 8 d. Leaves treated with melatonin maintained significantly higher endogenous melatonin level, chlorophyll content, photochemical efficiency, and cell membrane stability expressed by lower electrolyte leakage and malondialdehyde (MDA content compared to the control. Exogenous melatonin treatment also reduced the transcript level of chlorophyll degradation-associated genes and senescence marker genes (LpSAG12.1, Lph36, and Lpl69 during the dark treatment. The endogenous O2- production rate and H2O2 content were significantly lower in these excised leaves treated with melatonin compared to the water control. Exogenous melatonin treatment caused increases in enzymatic activity and transcript levels of superoxide dismutase and catalase but had no significant effects on ascorbate peroxidase, glutathione reductase, dehydroascorbate reductase, and monohydroascorbate reductase. The content of non-enzymatic antioxidants, such as ascorbate and dehydroascorbate, were decreased by melatonin treatment, while the content of glutathione and oxidized glutathione was not affected by melatonin. These results suggest that the suppression of dark-induced leaf senescence by exogenous melatonin may be associated with its roles in regulating ROS scavenging through activating the superoxide dismutase-catalase enzymatic antioxidant

  2. Malaria eradication: the economic, financial and institutional challenge

    Directory of Open Access Journals (Sweden)

    Hanson Kara

    2008-12-01

    Full Text Available Abstract Malaria eradication raises many economic, financial and institutional challenges. This paper reviews these challenges, drawing on evidence from previous efforts to eradicate malaria, with a special focus on resource-poor settings; summarizes more recent evidence on the challenges, drawing on the literature on the difficulties of scaling-up malaria control and strengthening health systems more broadly; and explores the implications of these bodies of evidence for the current call for elimination and intensified control. Economic analyses dating from the eradication era, and more recent analyses, suggest that, in general, the benefits of malaria control outweigh the costs, though few studies have looked at the relative returns to eradication versus long-term control. Estimates of financial costs are scanty and difficult to compare. In the 1960s, the consolidation phase appeared to cost less than $1 per capita and, in 1988, was estimated to be $2.31 per capita (both in 2006 prices. More recent estimates for high coverage of control measures suggest a per capita cost of several dollars. Institutional challenges faced by malaria eradication included limits to the rule of law (a major problem where malaria was concentrated in border areas with movement of people associated with illegal activities, the existence and performance of local implementing structures, and political sustainability at national and global levels. Recent analyses of the constraints to scaling-up malaria control, together with the historical evidence, are used to discuss the economic, financial and institutional challenges that face the renewed call for eradication and intensified control. The paper concludes by identifying a research agenda covering: ∘ issues of the allocative efficiency of malaria eradication, especially using macro-economic modelling to estimate the benefits and costs of malaria eradication and intensified control, and studies of the links between

  3. Deficiency of ATP2C1, a golgi ion pump, induces secretory pathway defects in endoplasmic reticulum ( ER)-associated degradation and sensitivity to ER stress

    NARCIS (Netherlands)

    Ramos-Castaneda, J; Park, YN; Liu, M; Hauser, K; Rudolph, H; Shull, GE; Jonkman, MF; Mori, K; Ikeda, S; Ogawa, H; Arvan, P

    2005-01-01

    Relatively few clues have been uncovered to elucidate the cell biological role(s) of mammalian ATP2C1 encoding an inwardly directed secretory pathway Ca2+/Mn2+ pump that is ubiquitously expressed. Deficiency of ATP2C1 results in a human disease ( Hailey-Hailey), which primarily affects keratinocytes

  4. Severe gastritis decreases success rate of Helicobacter pylori eradication.

    Science.gov (United States)

    Kalkan, Ismail Hakki; Sapmaz, Ferdane; Güliter, Sefa; Atasoy, Pınar

    2016-05-01

    In several studies, different risk factors other than antibiotic resistance have been documented with Helicobacter pylori eradication failure. We aimed in this study to investigate the relationship of gastric density of H. pylori, the occurrence/degree of gastric atrophy, and intestinal metaplasia (IM) with success rate of H. pylori eradication. Two hundred consecutive treatment naive patients who received bismuth containing standart quadruple treatment due to H. pylori infection documented by histopathological examination of two antral or two corpal biopsies entered this retrospective study. The updated Sydney system was used to grade the activity of gastritis, density of H. pylori colonization, atrophy, and IM. Stages III and IV of operative link for gastritis assessment (OLGA) or the operative link on gastric intestinal metaplasia assessment (OLGIM) stages was considered as severe gastritis. H. pylori eradication was determined via stool H. pylori antigen test performed 4 weeks after the end of therapy. The presence of gastric atrophy and IM was significantly higher in patients with eradication failure (p = 0.001 and 0.01, respectively). Severe gastritis (OLGA III-IV and OLGIM III-IV) rates were higher in eradication failure group. A multiple linear regression analysis showed that OLGA and OLGIM stages were to be independent risk factors for eradication failure (p = 0.03 and 0.01, respectively). Our results suggested that histopathologically severe gastritis may cause H. pylori eradication failure. In addition, we found that H. pylori density was not a risk factor for treatment failure in patients who receive quadruple treatment.

  5. MET Suppresses Epithelial VEGFR2 via Intracrine VEGF-induced Endoplasmic Reticulum-associated Degradation

    Directory of Open Access Journals (Sweden)

    Tom T. Chen

    2015-05-01

    Full Text Available Hepatocyte growth factor (HGF and vascular endothelial growth factor (VEGF drive cancer through their respective receptors, MET and VEGF receptor 2 (VEGFR2. VEGFR2 inhibits MET by promoting MET dephosphorylation. However, whether MET conversely regulates VEGFR2 remains unknown. Here we show that MET suppresses VEGFR2 protein by inducing its endoplasmic-reticulum-associated degradation (ERAD, via intracrine VEGF action. HGF–MET signaling in epithelial cancer cells promoted VEGF biosynthesis through PI3-kinase. In turn, VEGF and VEGFR2 associated within the ER, activating inositol-requiring enzyme 1α, and thereby facilitating ERAD-mediated depletion of VEGFR2. MET disruption upregulated VEGFR2, inducing compensatory tumor growth via VEGFR2 and MEK. However, concurrent disruption of MET and either VEGF or MEK circumvented this, enabling more profound tumor inhibition. Our findings uncover unique cross-regulation between MET and VEGFR2—two RTKs that play significant roles in tumor malignancy. Furthermore, these results suggest rational combinatorial strategies for targeting RTK signaling pathways more effectively, which has potentially important implications for cancer therapy.

  6. Metaproteogenomic analysis of a sulfate-reducing enrichment culture reveals genomic organization of key enzymes in the m-xylene degradation pathway and metabolic activity of proteobacteria.

    Science.gov (United States)

    Bozinovski, Dragana; Taubert, Martin; Kleinsteuber, Sabine; Richnow, Hans-Hermann; von Bergen, Martin; Vogt, Carsten; Seifert, Jana

    2014-10-01

    This study aimed to ascertain the functional and phylogenetic relationships within an m-xylene degrading sulfate-reducing enrichment culture, which had been maintained for several years in the laboratory with m-xylene as the sole source of carbon and energy. Previous studies indicated that a phylotype affiliated to the Desulfobacteraceae was the main m-xylene assimilating organism. In the present study, genes and gene products were identified by a metaproteogenomic approach using LC-MS/MS analysis of the microbial community, and 2426 peptides were identified from 576 proteins. In the metagenome of the community, gene clusters encoding enzymes involved in fumarate addition to a methyl moiety of m-xylene (nms, bss), as well as gene clusters coding for enzymes involved in modified beta-oxidation to (3-methyl)benzoyl-CoA (bns), were identified in two separate contigs. Additionally, gene clusters containing homologues to bam genes encoding benzoyl-CoA reductase (Bcr) class II, catalyzing the dearomatization of (3-methyl)benzoyl-CoA, were identified. Time-resolved protein stable isotope probing (protein-SIP) experiments using (13)C-labeled m-xylene showed that the respective gene products were highly (13)C-labeled. The present data suggested the identification of gene products that were similar to those involved in methylnaphthalene degradation even though the consortium was not capable of growing in the presence of naphthalene, methylnaphthalene or toluene as substrates. Thus, a novel branch of enzymes was found that was probably specific for anaerobic m-xylene degradation.

  7. Eliminating Late Recurrence to Eradicate Breast Cancer

    Science.gov (United States)

    2013-09-01

    6926–37 116. Yu WH, Cuervo AM, Kumar A, Peterhoff CM, Schmidt SD, et al. 2005. Macroautophagy—a novel β-amyloid peptide –generating pathway activated...Persistence of transcriptionally silent BCR-ABL rearrangements in chronic myeloid leukemia patients in sustained complete cytogenetic remission . Leuk Lymphoma...during interferon-induced remission in chronic myelogenous leukemia. Analysis by polymerase chain reaction of individual colonies. J Clin Invest. 1994; 94

  8. Organization and regulation of meta cleavage pathway genes for toluene and o-xylene derivative degradation in Pseudomonas stutzeri OX1.

    Science.gov (United States)

    Arenghi, F L; Berlanda, D; Galli, E; Sello, G; Barbieri, P

    2001-07-01

    Pseudomonas stutzeri OX1 meta pathway genes for toluene and o-xylene catabolism were analyzed, and loci encoding phenol hydroxylase, catechol 2,3-dioxygenase, 2-hydroxymuconate semialdehyde dehydrogenase, and 2-hydroxymuconate semialdehyde hydrolase were mapped. Phenol hydroxylase converted a broad range of substrates, as it was also able to transform the nongrowth substrates 2,4-dimethylphenol and 2,5-dimethylphenol into 3,5-dimethylcatechol and 3,6-dimethylcatechol, respectively, which, however, were not cleaved by catechol 2,3-dioxygenase. The identified gene cluster displayed a gene order similar to that of the Pseudomonas sp. strain CF600 dmp operon for phenol catabolism and was found to be coregulated by the tou operon activator TouR. A hypothesis about the evolution of the toluene and o-xylene catabolic pathway in P. stutzeri OX1 is discussed.

  9. Progress toward global eradication of dracunculiasis, January 2009-June 2010.

    Science.gov (United States)

    2010-10-01

    In 1986, the World Health Assembly (WHA) called for the elimination of dracunculiasis (Guinea worm disease), a parasitic infection in humans caused by Dracunculus medinensis. At the time, an estimated 3.5 million cases were occurring annually in 20 countries in Africa and Asia, and 120 million persons were at risk for the disease. Because of slow mobilization in countries with endemic disease, the 1991 WHA goal to eradicate dracunculiasis globally by 1995 was not achieved. In 2004, WHA established a new target date of 2009 for global eradication; despite considerable progress, that target date also was not met. This report updates both published and previously unpublished data and updates progress toward global eradication of dracunculiasis since January 2009. At the end of December 2009, dracunculiasis remained endemic in four countries (Ethiopia, Ghana, Mali, and Sudan). The number of indigenous cases of dracunculiasis worldwide had decreased 31%, from 4,613 in 2008 to 3,185 in 2009. Of the 766 cases that occurred during January--June 2010, a total of 745 (97%) were reported from 380 villages in Sudan. Ghana, Ethiopia, and Mali each are close to interrupting transmission, as indicated by the small and declining number of cases. The current target is to complete eradication in all four countries as quickly as possible. Insecurity (e.g., sporadic violence or civil unrest) in areas of Sudan and Mali where dracunculiasis is endemic poses the greatest threat to the success of the global dracunculiasis eradication program.

  10. Helicobacter pylori eradication therapy: A review of current trends.

    Science.gov (United States)

    Olokoba, A B; Obateru, O A; Bojuwoye, M O

    2013-01-01

    Helicobacter pylori has been implicated in the formation of chronic gastritis, peptic ulcer disease, mucosa-associated lymphoid tissue lymphoma and gastric cancer. Eradication of H. Pylori has been recommended as treatment and prevention for these complications. This review is based on a search of Medline, the Cochrane Database of Systemic Reviews, and citation lists of relevant publications. Subject heading and key words used include H. Pylori, current treatment and emerging therapy. Only articles in English were included. There has been a substantial decline in the H. pylori eradication rates over the years, despite the use of proton pump inhibitor and bismuth salts for triple and quadruple therapies respectively. The reasons for eradication failure are diverse, among them, antibiotic resistance is an important factor in the treatment failure. Primary resistance to clarithromycin or metronidazole significantly affects the efficacy of eradication therapy. This has led to the introduction of second line, third line "rescue," and sequential therapies for resistant cases. Subsequently, new antibiotic combinations with proton-pump inhibitors and bismuth salts are being studied in the last decade, to find out the antibiotics that are capable of increasing the eradication rates. Some of these antibiotics include Levofloxacin, Doxycycline, Rifaximin, Rifampicin, Furazolidone based therapies. Studies are ongoing to determine the efficacy of Lactoferrin based therapy.

  11. Helicobacter pylori eradication therapy: A review of current trends

    Directory of Open Access Journals (Sweden)

    A B Olokoba

    2013-01-01

    Full Text Available Helicobacter pylori has been implicated in the formation of chronic gastritis, peptic ulcer disease, mucosa-associated lymphoid tissue lymphoma and gastric cancer. Eradication of H. Pylori has been recommended as treatment and prevention for these complications. This review is based on a search of Medline, the Cochrane Database of Systemic Reviews, and citation lists of relevant publications. Subject heading and key words used include H. Pylori, current treatment and emerging therapy. Only articles in English were included. There has been a substantial decline in the H. pylori eradication rates over the years, despite the use of proton pump inhibitor and bismuth salts for triple and quadruple therapies respectively. The reasons for eradication failure are diverse, among them, antibiotic resistance is an important factor in the treatment failure. Primary resistance to clarithromycin or metronidazole significantly affects the efficacy of eradication therapy. This has led to the introduction of second line, third line "rescue," and sequential therapies for resistant cases. Subsequently, new antibiotic combinations with proton-pump inhibitors and bismuth salts are being studied in the last decade, to find out the antibiotics that are capable of increasing the eradication rates. Some of these antibiotics include Levofloxacin, Doxycycline, Rifaximin, Rifampicin, Furazolidone based therapies. Studies are ongoing to determine the efficacy of Lactoferrin based therapy.

  12. [The lost decade of global polio eradication and moving forward].

    Science.gov (United States)

    Shimizu, Hiroyuki

    2010-06-01

    The Global Polio Eradication Initiative was aimed to eradicate poliomyelitis by the year 2000, however, polio eradication is still not in sight even in 2010, over 10 years after the initial target date. In 2010, indigenous transmission of wild polioviruses has been interrupted throughout the world except four countries, Afghanistan, Pakistan, India, and Nigeria. Despite the intense use of monovalent oral polio vaccines, type 1 and type 3 wild polioviruses still circulate in the four remaining polio-endemic countries, and multiple importations of wild polioviruses have also occurred extensively from Nigeria and India to a number of previously polio-free countries in Africa, Asia, and Europe. Furthermore, the emergence of type 2 vaccine-derived polioviruses has raised concerns about low level of immunity against type 2 poliovirus in some polio-endemic areas like Nigeria and India. On the other hand, operational improvements in 2009 were reported in high-risk states in northern Nigeria and transmission of type 1 and type 3 polioviruses in Nigeria is markedly declining from 2009 to 2010. Moreover, bivalent oral polio vaccine containing Sabin 1 and Sabin 3 strains has been introduced in 2010 as a promising tool to improve and simplify the supplemental immunization activities in high-risk areas. Although there was no apparent decline in the annual number of polio cases in 2000-2009 globally, it would be critical to review our experience during "the lost decade of global polio eradication" to move forward into the final stage of global polio eradication.

  13. Eradication of poliomyelitis in countries affected by conflict.

    Science.gov (United States)

    Tangermann, R H; Hull, H F; Jafari, H; Nkowane, B; Everts, H; Aylward, R B

    2000-01-01

    The global initiative to eradicate poliomyelitis is focusing on a small number of countries in Africa (Angola, Democratic Republic of the Congo, Liberia, Sierra Leone, Somalia, Sudan) and Asia (Afghanistan, Tajikistan), where progress has been hindered by armed conflict. In these countries the disintegration of health systems and difficulties of access are major obstacles to the immunization and surveillance strategies necessary for polio eradication. In such circumstances, eradication requires special endeavours, such as the negotiation of ceasefires and truces and the winning of increased direct involvement by communities. Transmission of poliovirus was interrupted during conflicts in Cambodia, Colombia, El Salvador, Peru, the Philippines, and Sri Lanka. Efforts to achieve eradication in areas of conflict have led to extra health benefits: equity in access to immunization, brought about because every child has to be reached; the revitalization and strengthening of routine immunization services through additional externally provided resources; and the establishment of disease surveillance systems. The goal of polio eradication by the end of 2000 remains attainable if supplementary immunization and surveillance can be accelerated in countries affected by conflict.

  14. Epidermal Growth Factor Cytoplasmic Domain Affects ErbB Protein Degradation by the Lysosomal and Ubiquitin-Proteasome Pathway in Human Cancer Cells

    Directory of Open Access Journals (Sweden)

    Aleksandra Glogowska

    2012-05-01

    Full Text Available The cytoplasmic domains of EGF-like ligands, including EGF cytoplasmic domain (EGFcyt, have important biological functions. Using specific constructs and peptides of human EGF cytoplasmic domain, we demonstrate that EGFcyt facilitates lysosomal and proteasomal protein degradation, and this coincided with growth inhibition of human thyroid and glioma carcinoma cells. EGFcyt and exon 22–23-encoded peptide (EGF22.23 enhanced procathepsin B (procathB expression and procathB-mediated lysosomal degradation of EGFR/ErbB1 as determined by inhibitors for procathB and the lysosomal ATPase inhibitor BafA1. Presence of mbEGFctF, EGFcyt, EGF22.23, and exon 23-encoded peptides suppressed the expression of the deubiqitinating enzyme ubiquitin C-terminal hydrolase-L1 (UCH-L1. This coincided with hyperubiquitination of total cellular proteins and ErbB1/2 and reduced proteasome activity. Upon small interfering RNA-mediated silencing of endogenously expressed UCH-L1, a similar hyperubiquitinylation phenotype, reduced ErbB1/2 content, and attenuated growth was observed. The exon 23-encoded peptide region of EGFcyt was important for these biologic actions. Structural homology modeling of human EGFcyt showed that this molecular region formed an exposed surface loop. Peptides derived from this EGFcyt loop structure may aid in the design of novel peptide therapeutics aimed at inhibiting growth of cancer cells.

  15. Ecosystem services for meeting sustainable development goals: Challenges and pathways

    Directory of Open Access Journals (Sweden)

    Huq Nazmul

    2015-01-01

    Full Text Available The paper summarizes four presentations of the session “Environment and Wellbeing: The Role of Ecosystems for Sustainable Development” at the international conference “Sustainability in the Water- Energy-Food Nexus” held on 19-20th May 2014 in Bonn, Germany. The aim of the session was to present current stresses on ecosystem services imposed by global development trajectory, potential impacts on future Sustainable Development Goals (SDGs and pathways to achieve SDGs. All four presentations agreed that global ecosystem services are under increasing pressure from degradation and may not be able to meet the growing Water-Energy-Food (WEF demands especially for the developing world. Three examples from Tanzania, Cambodia and Niger made attempt to understand how government policies attributed to natural resource depletion such as forestry and common grazing. The examples showed that institutional policies favoring economic development contributing heavily to clearing up natural resource bases. As a result, there were increasing conflicts among different resource user groups. Two other presentations introduce conceptual pathways to achieve the targets of Sustainable Development Goals (SDGs under current resource stressed regime. The pathways suggested global technologies, decentralized solutions and consumption changes as the major means of achieving global sustainability and poverty eradication without any major trade-offs.

  16. Ecosystem services for meeting sustainable development goals: Challenges and pathways

    Directory of Open Access Journals (Sweden)

    Huq Nazmul

    2015-01-01

    Full Text Available The paper summarizes four presentations of the session “Environment and Wellbeing: The Role of Ecosystems for Sustainable Development” at the international conference “Sustainability in the Water- Energy-Food Nexus” held on 19-20th May 2014 in Bonn, Germany. The aim of the session was to present current stresses on ecosystem services imposed by global development trajectory, potential impacts on Sustainable Development Goals (SDGs and pathways to achieve SDGs. All four presentations agreed that global ecosystem services are under increasing pressure from degradation and may not be able to meet the growing Water-Energy- Food (WEF demands especially for the developing world. Three examples from Tanzania, Cambodia and Niger made attempt to understand how governance policies attributed to natural resource depletion such as forestry and common grazing. The examples showed that governance policies favoring economic development are heavily contributing to clearing up natural resource bases. As a result, there were increasing conflicts among different resource user groups. Two other presentations introduce conceptual pathways to achieve the targets of Sustainable Development Goals (SDGs under current resource stressed regime. The pathways suggested global technologies, decentralized solutions and consumption changes as the major means of achieving global sustainability and poverty eradication without any major trade-offs.

  17. Analysis of the Durability of PEM FC Membrane Electrode Assemblies in Automotive Applications through the Fundamental Understanding of Membrane and MEA Degradation Pathways

    Energy Technology Data Exchange (ETDEWEB)

    Perry, Randal L. [DuPont

    2013-10-31

    The Project focused on mitigation of degradation processes on membrane electrode assemblies. The approach was to develop a model to improve understanding of the mechanisms, and to use it to focus mitigation strategies. The detailed effects of various accelerated stress tests (ASTs) were evaluated to determine the best subset to use in model development. A combination of ASTs developed by the Fuel Cell Commercialization Conference of Japan and the Fuel Cell Tech Team were selected for use. The ASTs were compared by measuring effects on performance, running in-situ diagnostics, and performing microscopic analyses of the membrane electrode assemblies after the stress tests were complete. Nissan ran FCCJ AST protocols and performed in situ and ex-situ electrochemical testing. DuPont ran FCTT and USFCC AST protocols, performed scanning and transmission electron microscopy and ran in-situ electrochemical tests. Other ex-situ testing was performed by IIT, along with much of the data analysis and model development. These tests were then modified to generate time-dependent data of the degradation mechanisms. Three different catalyst types and four membrane variants were then used to generate data for a theoretically-based degradation model. An important part of the approach was to use commercially available materials in the electrodes and membranes made in scalable semiworks processes rather than lab-based materials. This constraint ensured all materials would be practicable for full-scale testing. The initial model for the electrode layer was tested for internal consistency and agreement with the data. A Java-based computer application was developed to analyze the time-dependent AST data using polarization curves with four different cathode gas feeds and generate model parameters. Data showed very good reproducibility and good consistency as cathode catalyst loadings were varied. At the point of termination of the project, a basic electrode model was in hand with several

  18. Challenges and key research questions for yaws eradication.

    Science.gov (United States)

    Marks, Michael; Mitjà, Oriol; Vestergaard, Lasse S; Pillay, Allan; Knauf, Sascha; Chen, Cheng-Yen; Bassat, Quique; Martin, Diana L; Fegan, David; Taleo, Fasihah; Kool, Jacob; Lukehart, Sheila; Emerson, Paul M; Solomon, Anthony W; Ye, Tun; Ballard, Ronald C; Mabey, David C W; Asiedu, Kingsley B

    2015-10-01

    Yaws is endemic in west Africa, southeast Asia, and the Pacific region. To eradicate yaws by 2020, WHO has launched a campaign of mass treatment with azithromycin. Progress has been made towards achievement of this ambitious goal, including the validation of point-of-care and molecular diagnostic tests and piloting of the strategy in several countries, including Ghana, Vanuatu, and Papua New Guinea. Gaps in knowledge need to be addressed to allow refinement of the eradication strategy. Studies exploring determinants of the spatial distribution of yaws are needed to help with the completion of baseline mapping. The finding that Haemophilus ducreyi causes lesions similar to yaws is particularly important and further work is needed to assess the effect of azithromycin on these lesions. The integration of diagnostic tests into different stages of the eradication campaign needs investigation. Finally, studies must be done to inform the optimum mass-treatment strategy for sustainable interruption of transmission.

  19. Current status of polio eradication and future prospects.

    Science.gov (United States)

    Thacker, Naveen; Shendurnikar, Niranjan

    2004-03-01

    The launch and the progress of global polio eradication initiative lead to a world wide decline of polio cases during the last few years. India shared this progress till 2001, when the number of reported cases were 268. Reversing this trend India reported 1599 cases during 2002 thereby accounting for nearly 87% of cases detected globally. Strategies for polio eradication are being revised after realizing that strategies such as fixed booth approach have not been sufficient to interrupt wild polio virus transmission. Increased number of NIDs and additional SNIDs are being planed to reach the previously unreached children. Low literacy levels, high poverty and resistance for OPV immunization in certain areas has further compounded the problem. As the progress in India is critical for the global polio eradication, maintenance of high routine immunization coverage, monitoring of SIA quality, AFP surveillance and laboratory investigations are vital for a successful outcome of this initiative.

  20. Global Campaign to Eradicate Insecurity of Tenure by 2030

    DEFF Research Database (Denmark)

    Enemark, Stig; McLaren, Robin

    2017-01-01

    The global eradication of infectious diseases through highly coordinated campaigns has been successful. Although insecurity of tenure is not a disease, its impact is devastating in terms of trapping people in poverty, displacing communities and making them homeless, and reducing food security...... and initiated? It is time for the land sector communities to be more ambitious in their goals, involve new partners to support innovation, adopt highly scalable approaches, collaborate more effectively under this common objective to eradicate this scourge on the earth and create land rights for all....... This proposed global campaign could well be the necessary catalyst for change. The paper initially investigates the drivers that are emerging at the highest levels to raise the necessity and urgency to initiate a scalable, global campaign to eradicate insecurity of tenure. The paper then discusses how...

  1. Prevention of Gastric Cancer: Eradication of Helicobacter Pylori and Beyond

    Directory of Open Access Journals (Sweden)

    Tetsuya Tsukamoto

    2017-08-01

    Full Text Available Although its prevalence is declining, gastric cancer remains a significant public health issue. The bacterium Helicobacter pylori is known to colonize the human stomach and induce chronic atrophic gastritis, intestinal metaplasia, and gastric cancer. Results using a Mongolian gerbil model revealed that H. pylori infection increased the incidence of carcinogen-induced adenocarcinoma, whereas curative treatment of H. pylori significantly lowered cancer incidence. Furthermore, some epidemiological studies have shown that eradication of H. pylori reduces the development of metachronous cancer in humans. However, other reports have warned that human cases of atrophic metaplastic gastritis are already at risk for gastric cancer development, even after eradication of these bacteria. In this article, we discuss the effectiveness of H. pylori eradication and the morphological changes that occur in gastric dysplasia/cancer lesions. We further assess the control of gastric cancer using various chemopreventive agents.

  2. [Significance of ursodeoxycholic acid in the eradication of Helicobacter pylori].

    Science.gov (United States)

    Binek, J; Hildebrand, P; Beglinger, C

    1996-01-01

    In this pilot study we investigated the value of a fourteen-day regimen with amoxicillin (1 g bid), ranitidine (300 mg/d) and ursodeoxycholic acid (300 mg tid) in eradicating Helicobacter pylori. 15 patients with non-ulcer dyspepsia (reactive CLO test, positive histology or 13C urea breath test) were enrolled. Helicobacter pylori was eradicated in 6 of 13 patients (13C urea breath test 4 weeks after the end of treatment). 2 patients were not followed up because of too short treatment (< 1 week). Only 5/15 patients had no side effects (33%). These results strongly suggest that ursodeoxycholic acid in this application regimen is not of use in eradicating Helicobacter pylori.

  3. 河道底泥中四溴双酚A厌氧降解及代谢途径%Anaerobic degradation and pathways of tetrabromobisphenol A in river sediments

    Institute of Scientific and Technical Information of China (English)

    李玲玲; 刘世诚; 朱崇岭; 任源; 岑锦涛

    2014-01-01

    采用血清瓶实验研究了3种河道底泥(新造、清远和贵屿镇)中四溴双酚A( TBBPA)厌氧降解特性,结果表明,不同河道底泥TBBPA降解速率有差异,作为垃圾拆解地的贵屿河道底泥降解速率最快,添加电子供体能加快TBBPA的降解.TBBPA厌氧降解符合拟一级动力学,50μmol·L-1 TBBPA降解速率为0.0491 d-1,对应半衰期为16.0 d;降解速率与TBBPA初始浓度成反比,高浓度下抑制微生物活动,从而影响TBBPA降解速率.采用UPLC-MS/MS分析TBBPA降解中间产物,发现与3,3′,5-三溴双酚A( tri-BBPA)、3-溴双酚A( mono-BBPA)以及双酚A( BPA)对应的特征质子图谱,从而推测TBBPA在厌氧条件下的转化途径为经由三溴双酚A、一溴双酚A、生成双酚A.%Tetrabromobisphenol A ( TBBPA) is a kind of widely used brominated flame retardants throughout the world and presented in the environment ubiquitously. This study investigated the anaerobic degradation of TBBPA in three river sediments ( Xinzao, Qingyuan, and Guiyu Town in Guangdong Province) by conducting serum bottle experiments. The results showed that the three sediments had different degradation capabilities, and the sediment in Guiyu Town, an E-waste dismantling site, had the highest TBBPA anaerobic degradation rate. Moreover, The addition of electron donors can enhance the debromination of TBBPA. The half-lives (t1/2) of TBBPA anaerobic degradation in the sediments were 16. 0 d,39. 7 d, and 84. 1 d at concentrations of 50, 100, and 200 μmol·L-1, respectively. High concentration TBBPA inhibited debromination process. Furthermore, 3,3′,5-tribromobisphenol A ( tri-BBPA) , 3-monobromobisphenol A ( mono-BBPA) , and bisphenol A ( BPA) were detected through UPLC-MS/MS method. The following pathway of TBBPA degradation in anaerobic sediments was proposed:TBBPA-tri-BBPA-mono-BBPA-BPA.

  4. Helicobacter pylori eradication as a preventive tool against gastric cancer.

    Science.gov (United States)

    Hamajima, Nobuyuki; Goto, Yasuyuki; Nishio, Kazuko; Tanaka, Daisuke; Kawai, Sayo; Sakakibara, Hisataka; Kondo, Takaaki

    2004-01-01

    Helicobacter pylori (H. pylori), which increases the risk of gastric diseases, including digestive ulcers and gastric cancer, is highly prevalent in Asian countries. There is no doubt that eradication of the bacterium is effective as a treatment of digestive ulcer, but eradication aiming to reduce the gastric cancer risk is still controversial. Observational studies in Japan demonstrated that the eradication decreased the gastric cancer risk among 132 stomach cancer patients undergoing endoscopical resection (65 treated with omeprazol and antibiotics and 67 untreated). In Columbia, 976 participants were randomized into eight groups in a three-treatment factorial design including H. pylori eradication, resulting in significant regression in the H. pylori eradication group. A recent randomized study in China also showed a significant reduction of gastric cancer risk among those without any gastric atrophy, intestinal metaplasia, and dysplasia. Efficacy of eradication may vary in extent among countries with different incidence rates of gastric cancer. Since the lifetime cumulative risk (0 to 84 years old) of gastric cancer in Japan is reported to be 12.7% for males and 4.8% for females (Inoue and Tominaga, 2003), the corresponding values for H. pylori infected Japanese can be estimated at 21.2% in males and 8.0% in females under the assumptions that the relative risk for infected relative to uninfected is 5 and the proportion of those infected is 0.5. Both the fact that not all individuals are infected among those exposed and the knowledge that only a small percentage of individuals infected with the bacterium develop gastric cancer, indicate the importance of gene-environment interactions. Studies on such interactions should provide useful information for anti-H. pylori preventive strategies.

  5. Regulation of alkane degradation pathway by a TetR family repressor via an autoregulation positive feedback mechanism in a Gram-positive Dietzia bacterium.

    Science.gov (United States)

    Liang, Jie-Liang; Nie, Yong; Wang, Miaoxiao; Xiong, Guangming; Wang, Yi-Ping; Maser, Edmund; Wu, Xiao-Lei

    2016-01-01

    n-Alkanes are ubiquitous in nature and serve as important carbon sources for both Gram-positive and Gram-negative bacteria. Hydroxylation of n-alkanes by alkane monooxygenases is the first and most critical step in n-alkane metabolism. However, regulation of alkane degradation genes in Gram-positive bacteria remains poorly characterized. We therefore explored the transcriptional regulation of an alkB-type alkane hydroxylase-rubredoxin fusion gene, alkW1, from Dietzia sp. DQ12-45-1b. The alkW1 promoter was characterized and so was the putative TetR family regulator, AlkX, located downstream of alkW1 gene. We further identified an unusually long 48 bp inverted repeat upstream of alkW1 and demonstrated the binding of AlkX to this operator. Analytical ultracentrifugation and microcalorimetric results indicated that AlkX formed stable dimers in solution and two dimers bound to one operator in a positive cooperative fashion characterized by a Hill coefficient of 1.64 (± 0.03) [k(D)  = 1.06 (± 0.16) μM, k(D) ' = 0.05 (± 0.01) μM]. However, the DNA-binding affinity was disrupted in the presence of long-chain fatty acids (C10-C24), suggesting that AlkX can sense the concentrations of n-alkane degradation metabolites. A model was therefore proposed where AlkX controls alkW1 expression in a metabolite-dependent manner. Bioinformatic analysis revealed that the alkane hydroxylase gene regulation mechanism may be common among Actinobacteria.

  6. Rhodococcus sp.BX2菌对乙腈的降解特性及降解途径研究%Characteristics and pathway of acetonitrile degradation by Rhodococcus sp.BX2

    Institute of Scientific and Technical Information of China (English)

    孙晶; 熊明华; 成小松; 李悦; 臧海莲; 李春艳

    2012-01-01

    对Rhodococcus sp.BX2菌降解乙腈的特性及其降解途径进行了研究.结果显示,在底物浓度为800mg·L-1,接种量为1.0%,培养温度为35℃,环境pH为7.5的条件下,16h时Rhodococcus sp.BX2菌对乙腈的降解率为95.98%;添加葡萄糖可在培养初期加快Rhodococcus sp.BX2菌的生长和对乙腈的降解,蔗糖、乙酰胺和尿素对其影响不大.将BX2菌接种到含有高乙腈浓度(25000mg·L-1)的合成废水中,培养180h后,乙腈降解率可达88.59%.在催化反应60min后,Rhodococcus sp.BX2腈水合酶与腈水解酶的总酶活可达到422.81U·mL-1,对其相关基因序列的分析结果表明,Rhodococcus sp.BX2中同时存在腈水解酶基因和腈水合酶基因,因此,确定乙腈的降解主要由腈水合酶途径完成,可能同时存在腈水解酶的降解途径.%The characteristics and pathway of acetonitrile degradation by Rhodococcus sp.BX2 were investigated in this study. Results showed that with the initial acetonitrile concentration of 800 mg · L-1, the degradation rate was 95.98% in 16 hours under the condition of inoculum 1.0%, 35 ℃ and pH value 7.5.Glucose could accelerate the degradation of acetonitrile in the initial period, while sucrose, acetamide and urea had slight impact. The degradation rate could reach 88.59% when BX2 was cultured in the synthetic wastewater with high concentration of acetonitrile (25000 mg · L-1) for 180 hours. Total enzyme activities was 422.81 U · mL-1 when incubated for 60 minutes. The results of related genes sequence showed that Rhodococcus sp BX2 had both nitrile hydrolase gene and nitrile hydratase gene. The degradation pathway of acetonitrile by Rhodococcus sp. BX2 was mainly nitrile hydratase (NHase), with possible pathway of the nitrile hydrolase.

  7. Microbial Degradation of Cellular Kinases Impairs Innate Immune Signaling and Paracrine TNFα Responses.

    Science.gov (United States)

    Barth, Kenneth; Genco, Caroline Attardo

    2016-10-04

    The NFκB and MAPK signaling pathways are critical components of innate immunity that orchestrate appropriate immune responses to control and eradicate pathogens. Their activation results in the induction of proinflammatory mediators, such as TNFα a potent bioactive molecule commonly secreted by recruited inflammatory cells, allowing for paracrine signaling at the site of an infection. In this study we identified a novel mechanism by which the opportunistic pathogen Porphyromonas gingivalis dampens innate immune responses by disruption of kinase signaling and degradation of inflammatory mediators. The intracellular immune kinases RIPK1, TAK1, and AKT were selectively degraded by the P. gingivalis lysine-specific gingipain (Kgp) in human endothelial cells, which correlated with dysregulated innate immune signaling. Kgp was also observed to attenuate endothelial responsiveness to TNFα, resulting in a reduction in signal flux through AKT, ERK and NFκB pathways, as well as a decrease in downstream proinflammatory mRNA induction of cytokines, chemokines and adhesion molecules. A deficiency in Kgp activity negated decreases to host cell kinase protein levels and responsiveness to TNFα. Given the essential role of kinase signaling in immune responses, these findings highlight a unique mechanism of pathogen-induced immune dysregulation through inhibition of cell activation, paracrine signaling, and dampened cellular proinflammatory responses.

  8. Construction of Hemoglobin Degradation Pathway of Schistosoma and Analysis of Conserved Domains of Pathway Key Enzymes%血吸虫血红蛋白降解途径的重构及关键酶蛋白保守结构域的分析

    Institute of Scientific and Technical Information of China (English)

    魏佳; 李园园; 李亦学; 于复东

    2011-01-01

    On the basis of hemoglobin degradation pathway of Plasmodium falciparum, hemoglobin degradation pathways of Schistosoma japonicum and Schistosoma mansoni were constructed using bioinformatic methods. Sequences and structures of conserved domains of pathway key enzymes were analyzed after pathway construction. The catalytic sites of predicted hemoglobinases of Schistosoma are highly conserved with Plasmodium in both sequence and structure level. This paper provides a theoretical foundation for Schistosoma hemoglobinase study, and analysis of their interactions with substrates or inhibitors in three-dimensional level.%利用生物信息学方法,以疟原虫的血红蛋白降解途径为基础,成功地构建出了日本血吸虫和曼氏血吸虫的血红蛋白降解途径,并对降解途径上的关键酶蛋白的保守结构域进行了序列及结构分析。预测得到的血吸虫血红蛋白降解酶保守结构域,与疟原虫相比,在序列上催化位点高度保守,在结构上空间相对位置较一致,为研究血吸虫血红蛋白降解酶,及其与底物或抑制剂在三维结构上的相互作用提供了理论基础。

  9. GBF1, a transcription factor of blue light signaling in Arabidopsis, is degraded in the dark by a proteasome-mediated pathway independent of COP1 and SPA1.

    Science.gov (United States)

    Mallappa, Chandrashekara; Singh, Aparna; Ram, Hathi; Chattopadhyay, Sudip

    2008-12-19

    Arabidopsis GBF1/ZBF2 is a bZIP transcription factor that plays dual but opposite regulatory roles in cryptochrome-mediated blue light signaling. Here, we show the genetic and molecular interrelation of GBF1 with two well characterized negative regulators of light signaling, COP1 and SPA1, in photomorphogenic growth and light-regulated gene expression. Our results further reveal that GBF1 protein is less abundant in the dark-grown seedlings and is degraded by a proteasome-mediated pathway independent of COP1 and SPA1. Furthermore, COP1 physically interacts with GBF1 and is required for the optimum accumulation of GBF1 protein in light-grown seedlings. Taken together, this study provides a mechanistic view of concerted function of three important regulators in Arabidopsis seedling development.

  10. India's poliomyelitis eradication: a milestone in public health.

    Science.gov (United States)

    Grover, Manoj; Bhatnagar, Nidhi; Sinha, Smita; Kaur, Ravneet

    2013-12-01

    India has recently completed 2 years without single case of poliomyelitis on 13 January 2013. This has brought South East Asian Region closer to eradication. Recently, India is being regarded as a role model for polio eradication efforts in other low-income endemic countries-Pakistan, Nigeria and Afghanistan. However, the near elimination of wild polio virus in India has set forth newer challenges. Stricter surveillance measures are now needed to check for importations spread of virus in migratory populations and rapid containment of newly found virus. India's battle against polio will soon be cited as biggest public health achievement or most expensive public health failure.

  11. Tetrahydrohyperforin Inhibits the Proteolytic Processing of Amyloid Precursor Protein and Enhances Its Degradation by Atg5-Dependent Autophagy.

    Directory of Open Access Journals (Sweden)

    Viviana A Cavieres

    Full Text Available Alzheimer's disease (AD is a neurodegenerative disorder characterized by the accumulation of amyloid-β (Aβ peptide. We have previously shown that the compound tetrahydrohyperforin (IDN5706 prevents accumulation of Aβ species in an in vivo model of AD, however the mechanism that explains this reduction is not well understood. We show herein that IDN5706 decreases the levels of ER degradation enhancer, mannosidase alpha-like 1 (EDEM1, a key chaperone related to endoplasmic-reticulum-associated degradation (ERAD. Moreover, we observed that low levels of EDEM1 correlated with a strong activation of autophagy, suggesting a crosstalk between these two pathways. We observed that IDN5706 perturbs the glycosylation and proteolytic processing of the amyloid precursor protein (APP, resulting in the accumulation of immature APP (iAPP in the endoplasmic reticulum. To investigate the contribution of autophagy, we tested the effect of IDN5706 in Atg5-depleted cells. We found that depletion of Atg5 enhanced the accumulation of iAPP in response to IDN5706 by slowing down its degradation. Our findings reveal that IDN5706 promotes degradation of iAPP via the activation of Atg5-dependent autophagy, shedding light on the mechanism that may contribute to the reduction of Aβ production in vivo.

  12. Tetrahydrohyperforin Inhibits the Proteolytic Processing of Amyloid Precursor Protein and Enhances Its Degradation by Atg5-Dependent Autophagy

    Science.gov (United States)

    Muñoz, Vanessa C.; Yefi, Claudia P.; Bustamante, Hianara A.; Barraza, Rafael R.; Tapia-Rojas, Cheril; Otth, Carola; Barrera, María José; González, Carlos; Mardones, Gonzalo A.; Inestrosa, Nibaldo C.; Burgos, Patricia V.

    2015-01-01

    Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the accumulation of amyloid-β (Aβ) peptide. We have previously shown that the compound tetrahydrohyperforin (IDN5706) prevents accumulation of Aβ species in an in vivo model of AD, however the mechanism that explains this reduction is not well understood. We show herein that IDN5706 decreases the levels of ER degradation enhancer, mannosidase alpha-like 1 (EDEM1), a key chaperone related to endoplasmic-reticulum-associated degradation (ERAD). Moreover, we observed that low levels of EDEM1 correlated with a strong activation of autophagy, suggesting a crosstalk between these two pathways. We observed that IDN5706 perturbs the glycosylation and proteolytic processing of the amyloid precursor protein (APP), resulting in the accumulation of immature APP (iAPP) in the endoplasmic reticulum. To investigate the contribution of autophagy, we tested the effect of IDN5706 in Atg5-depleted cells. We found that depletion of Atg5 enhanced the accumulation of iAPP in response to IDN5706 by slowing down its degradation. Our findings reveal that IDN5706 promotes degradation of iAPP via the activation of Atg5-dependent autophagy, shedding light on the mechanism that may contribute to the reduction of Aβ production in vivo. PMID:26308941

  13. Isolation,identification,degradation characteristics and pathway of a pyrethroid-degrading bacterial strain%一株拟除虫菊酯农药降解菌的分离鉴定及其降解特性与途径

    Institute of Scientific and Technical Information of China (English)

    陈少华; 罗建军; 胡美英; 赖开平; 耿鹏; 肖盈

    2011-01-01

    A bacterial strain named P-01 was newly isolated by enrichment culture from the activated sludge in the wastewater of a pyrethroid-manufacturer in Zhongshan.Based on the morphology,physio-biochemical characteristics,and 16S rDNA sequence analysis,strain P-01 was temporarily identified as Achromobacter sp.P-01.Response surface methodology(RSM) was used to optimize degradation conditions.The optimal conditions for biodegradation were obtained as follows:31.4℃,pH 7.6 and inoculum biomass 0.4 g · L-1.Under the optimal degradation conditions,strain P-01 could effectively degrade deltamethrin,fenvalerate,beta-cypermethrin,beta-cyfluthrin and cyhalothrin with degradation rates of 98.9%,92.2%,91.0%,85.1% and 77.3%,respectively,within 7 days of incubation.Strain P-01 not only could utilize deltamethrin as the sole carbon source and energy for growth in mineral salt medium(MSM),but also could tolerate and efficiently degrade high concentrations of deltamethrin(100~500 mg · L-1).Furthermore,the degradation reaction followed first-order kinetics and half lives(T1/2) were 1.3,1.8,2.0,2.5 and 3.0 d,respectively.Studies on the degradation pathway showed that deltamethrin was degraded by hydrolysis of the carboxylester linkage to yield alpha-hydroxy-3-phenoxy-benzeneacetonitrile and 3-phenoxy benzaldehyde,and then the intermediates were further degraded by oxygenolysis to form 2-hydroxy-4-methoxy benzophenone and 1,2-benzenedicarboxylic acid,mono ester,finally resulting in complete detoxification.%采用富集培养法,从拟除虫菊酯农药厂废水排放口的活性污泥中分离到1株菊酯农药高效降解菌P-01.经形态、生理生化特征及16S rDNA序列分析,初步鉴定其为无色杆菌属(Achromobacter sp.).响应曲面法优化菌株P-01的降解条件,其降解最优条件为31.4℃、初始pH7.6和接种量0.4g·L-1,在此条件下,该菌株培养7d对50mg·L-1溴氰菊酯、氰戊菊酯、高效氯氰菊酯、高效氟

  14. The effect of probiotics supplementation on Helicobacter pylori eradication rates and side effects during eradication therapy: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Yini Dang

    Full Text Available BACKGROUND: Previous meta-analyses reported that probiotics improve the effectiveness of Helicobacter pylori (H. pylori eradication during antibiotic therapy, while results regarding a possible reduction of side effects remained inconclusive. Moreover, the effectiveness of different strains of probiotics has not been studied so far. It is further conceivable that probiotics will produce additional effects only if antibiotics are relatively ineffective. METHODS: This meta-analysis includes eligible randomized controlled trials examining effects of probiotics supplementation on eradication rates (ER and side effects, published up to May 2014. Sub-group analysis was performed to compare different probiotic strains and antibiotic therapies with different effectiveness in controls (ER 80%. Publication bias was assessed with funnel plots and Harbord's test. The quality of the trials was assessed with the Cochrane risk of bias tool. RESULTS: Thirty-three RCTs involving a total of 4459 patients met the inclusion criteria in case of eradication rates of which 20 assessed total side effects in addition. Overall, the pooled eradication rate in probiotics supplementation groups was significantly higher than in controls (ITT analysis: RR 1.122, 95% CI 1.086-1.159, PP analysis: RR 1.114, 95% CI 1.070-1.159. Sub group-analysis could, however, confirm this finding only for four individual strains (Lactobacillus acidophilus, Lactobacillus casei DN-114001, Lactobacillus gasseri, and Bifidobacterium infantis 2036 and for relatively ineffective antibiotic therapies. There was a significant difference between groups in the overall incidence of side effects (RR 0.735, 95% CI 0.598-0.902. This result was, however, only confirmed for non-blinded trials. CONCLUSIONS: The pooled data suggest that supplementation with specific strains of probiotics compared with eradication therapy may be considered an option for increasing eradication rates, particularly when antibiotic

  15. Congenital cataract causing mutants of αA-crystallin/sHSP form aggregates and aggresomes degraded through ubiquitin-proteasome pathway.

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    Ilangovan Raju

    Full Text Available BACKGROUND: Mutations of human αA-crystallin cause congenital cataract by protein aggregation. How mutations of αA-crystallin cause disease pathogenesis through protein aggregation is not well understood. To better understand the cellular events leading to protein aggregation, we transfected cataract causing mutants, R12C, R21L, R21W, R49C, R54C, R116C and R116H, of human αA-crystallin in HeLa cells and examined the formation of intracellular protein aggregates and aggresomes by confocal microscopy. METHODOLOGY/PRINCIPAL FINDINGS: YFP-tagged human αA-wild-type (αA-wt was sub-cloned and the mutants were generated by site-directed mutagenesis. The αA-wt and the mutants were individually transfected or co-transfected with CFP-tagged αA-wt or αB-wild-type (αB-wt in HeLa cells. Overexpression of these mutants forms multiple small dispersed cytoplasmic aggregates as well as aggresomes. Co-expression of αB-wt with these mutants significantly inhibited protein aggregates where as co-expression with αA-wt enhanced protein aggregates which seems to be due to co-aggregation of the mutants with αA-wt. Aggresomes were validated by double immunofluorescence by co-localization of γ-tubulin, a centrosome marker protein with αA-crystallin. Furthermore, increased ubiquitination was detected in R21W, R116C and R116H as assessed by western blot analyses. Immunostaining with an ubiquitin antibody revealed that ubiquitin inclusions in the perinuclear regions were evident only in R116C transfected cells. Pulse chase assay, after cycloheximide treatment, suggested that R116C degraded faster than the wild-type control. CONCLUSIONS/SIGNIFICANCE: Mutants of αA-crystallin form aggregates and aggresomes. Co-expression of αA-wt with the mutants increased aggregates and co-expression of αB-wt with the mutants significantly decreased the aggregates. The mutant, R116C protein degraded faster than wild-type control and increased ubiquitination was evident in R

  16. Microbial Degradation of Indole and Its Derivatives

    Directory of Open Access Journals (Sweden)

    Pankaj Kumar Arora

    2015-01-01

    Full Text Available Indole and its derivatives, including 3-methylindole and 4-chloroindole, are environmental pollutants that are present worldwide. Microbial degradation of indole and its derivatives can occur in several aerobic and anaerobic pathways; these pathways involve different known and characterized genes. In this minireview, we summarize and explain the microbial degradation of indole, indole-3-acetic acid, 4-chloroindole, and methylindole.

  17. TRANSFORMING GROWTH FACTOR-β1 AND SMAD4 SIGNALING PATHWAY DOWN-REGULATES RENAL EXTRACELLULAR MATRIX DEGRADATION IN DIABETIC RATS

    Institute of Scientific and Technical Information of China (English)

    Qin Yang; Ru-jia Xie; Ting Yang; Li Fang; Bing Han; Guo-zhong Zhang; Ming-liang Cheng

    2007-01-01

    To investigate the role of transforming growth factor-β1 ( TGF-β1 )/Smad4 pathway in development of renal fibrosis in streptozotocin (STZ)-induced diabetic nephropathy (DN) rats and explore its possible mechanism.Methods Male Wistar rats weighing 180-220 g were divided into 5 groups: group A ( normal control), group B[ diabetes mellitus (DM) 2 weeks], group C (DM4 weeks), group D (DM 8 weeks), and group E (DM 16 weeks).Except for the normal control group, other groups were induced DM by single injection of STZ (55 mg/kg) respectively. Blood glucose level, serum creatinine, and 24-hour urine protein were examined. Expressions of TGF-β1 and Smad4 protein and mRNA in kidney were detected using immunohistochemical technique, Western blot, and real-time PCR. mRNA expressions of stromelysin-1 ( MMP-3 ), tissue inhibitor of metalloproteinase-1 ( TIMP-1 ), and collagen Ⅲ in kidney were also detected by real-time PCR..Results The levels of blood glucose, serum creatinine, and 24-hour urine protein in rats of group B, C, D, and E were higher than those of the control group. With the progression of renal fibrosis, the expressions of TGF-β1 and Smad4 protein and mRNA in kidney of diabetic rats elevated. In addition, the renal MMP-3 mRNA expression diminished in diabetic rats, while TIMP-1 and collagen Ⅲ mRNA increased.Conclusions In STZ-induced diabetic rats, the TGF-β1/Smad4 appears to play an important role in renal fibrosis of DN. The increased expression of TGF-β1 and Smad4 might result in the transcriptional regulation of downstream target genes of TGF-β1/Smad4 pathway, which contributes to the progression of renal fibrosis in diabetic rats.

  18. Potential of environmental DNA to evaluate Northern pike (Esox lucius) eradication efforts: An experimental test and case study

    Science.gov (United States)

    Dunker, Kristine J.; Sepulveda, Adam; Massengill, Robert L.; Olsen, Jeffrey B.; Russ, Ora L.; Wenburg, John K.; Antonovich, Anton

    2016-01-01

    Determining the success of invasive species eradication efforts is challenging because populations at very low abundance are difficult to detect. Environmental DNA (eDNA) sampling has recently emerged as a powerful tool for detecting rare aquatic animals; however, detectable fragments of DNA can persist over time despite absence of the targeted taxa and can therefore complicate eDNA sampling after an eradication event. This complication is a large concern for fish eradication efforts in lakes since killed fish can sink to the bottom and slowly decay. DNA released from these carcasses may remain detectable for long periods. Here, we evaluated the efficacy of eDNA sampling to detect invasive Northern pike (Esox lucius) following piscicide eradication efforts in southcentral Alaskan lakes. We used field observations and experiments to test the sensitivity of our Northern pike eDNA assay and to evaluate the persistence of detectable DNA emitted from Northern pike carcasses. We then used eDNA sampling and traditional sampling (i.e., gillnets) to test for presence of Northern pike in four lakes subjected to a piscicide-treatment designed to eradicate this species. We found that our assay could detect an abundant, free-roaming population of Northern pike and could also detect low-densities of Northern pike held in cages. For these caged Northern pike, probability of detection decreased with distance from the cage. We then stocked three lakes with Northern pike carcasses and collected eDNA samples 7, 35 and 70 days post-stocking. We detected DNA at 7 and 35 days, but not at 70 days. Finally, we collected eDNA samples ~ 230 days after four lakes were subjected to piscicide-treatments and detected Northern pike DNA in 3 of 179 samples, with a single detection at each of three lakes, though we did not catch any Northern pike in gillnets. Taken together, we found that eDNA can help to inform eradication efforts if used in conjunction with multiple lines of inquiry and sampling

  19. Potential of Environmental DNA to Evaluate Northern Pike (Esox lucius) Eradication Efforts: An Experimental Test and Case Study.

    Science.gov (United States)

    Dunker, Kristine J; Sepulveda, Adam J; Massengill, Robert L; Olsen, Jeffrey B; Russ, Ora L; Wenburg, John K; Antonovich, Anton

    2016-01-01

    Determining the success of invasive species eradication efforts is challenging because populations at very low abundance are difficult to detect. Environmental DNA (eDNA) sampling has recently emerged as a powerful tool for detecting rare aquatic animals; however, detectable fragments of DNA can persist over time despite absence of the targeted taxa and can therefore complicate eDNA sampling after an eradication event. This complication is a large concern for fish eradication efforts in lakes since killed fish can sink to the bottom and slowly decay. DNA released from these carcasses may remain detectable for long periods. Here, we evaluated the efficacy of eDNA sampling to detect invasive Northern pike (Esox lucius) following piscicide eradication efforts in southcentral Alaskan lakes. We used field observations and experiments to test the sensitivity of our Northern pike eDNA assay and to evaluate the persistence of detectable DNA emitted from Northern pike carcasses. We then used eDNA sampling and traditional sampling (i.e., gillnets) to test for presence of Northern pike in four lakes subjected to a piscicide-treatment designed to eradicate this species. We found that our assay could detect an abundant, free-roaming population of Northern pike and could also detect low-densities of Northern pike held in cages. For these caged Northern pike, probability of detection decreased with distance from the cage. We then stocked three lakes with Northern pike carcasses and collected eDNA samples 7, 35 and 70 days post-stocking. We detected DNA at 7 and 35 days, but not at 70 days. Finally, we collected eDNA samples ~ 230 days after four lakes were subjected to piscicide-treatments and detected Northern pike DNA in 3 of 179 samples, with a single detection at each of three lakes, though we did not catch any Northern pike in gillnets. Taken together, we found that eDNA can help to inform eradication efforts if used in conjunction with multiple lines of inquiry and sampling

  20. Catechins and Sialic Acid Attenuate Helicobacter pylori-Triggered Epithelial Caspase-1 Activity and Eradicate Helicobacter pylori Infection

    Directory of Open Access Journals (Sweden)

    Jyh-Chin Yang

    2013-01-01

    Full Text Available The inflammasome/caspase-1 signaling pathway in immune cells plays a critical role in bacterial pathogenesis; however, the regulation of this pathway in the gastric epithelium during Helicobacter pylori infection is yet to be elucidated. Here, we investigated the effect of catechins (CAs, sialic acid (SA, or combination of CA and SA (CASA on H. pylori-induced caspase-1-mediated epithelial damage, as well as H. pylori colonization in vitro (AGS cells and in vivo (BALB/c mice. Our results indicate that the activity of caspase-1 and the expression of its downstream substrate IL-1β were upregulated in H. pylori-infected AGS cells. In addition, we observed increased oxidative stress, NADPH oxidase gp91phox, CD68, caspase-1/IL-1β, and apoptosis, but decreased autophagy, in the gastric mucosa of H. pylori-infected mice. We have further demonstrated that treatment with CASA led to synergistic anti-H. pylori activity and was more effective than treatment with CA or SA alone. In particular, treatment with CASA for 10 days eradicated H. pylori infection in up to 95% of H. pylori-infected mice. Taken together, we suggest that the pathogenesis of H. pylori involves a gastric epithelial inflammasome/caspase-1 signaling pathway, and our results show that CASA was able to attenuate this pathway and effectively eradicate H. pylori infection.

  1. From emergence to eradication: the epidemiology of poliomyelitis deconstructed.

    Science.gov (United States)

    Nathanson, Neal; Kew, Olen M

    2010-12-01

    Poliomyelitis has appeared in epidemic form, become endemic on a global scale, and been reduced to near-elimination, all within the span of documented medical history. Epidemics of the disease appeared in the late 19th century in many European countries and North America, following which polio became a global disease with annual epidemics. During the period of its epidemicity, 1900-1950, the age distribution of poliomyelitis cases increased gradually. Beginning in 1955, the creation of poliovirus vaccines led to a stepwise reduction in poliomyelitis, culminating in the unpredicted elimination of wild polioviruses in the United States by 1972. Global expansion of polio immunization resulted in a reduction of paralytic disease from an estimated annual prevaccine level of at least 600,000 cases to fewer than 1,000 cases in 2000. Indigenous wild type 2 poliovirus was eradicated in 1999, but unbroken localized circulation of poliovirus types 1 and 3 continues in 4 countries in Asia and Africa. Current challenges to the final eradication of paralytic poliomyelitis include the continued transmission of wild polioviruses in endemic reservoirs, reinfection of polio-free areas, outbreaks due to circulating vaccine-derived polioviruses, and persistent excretion of vaccine-derived poliovirus by a few vaccinees with B-cell immunodeficiencies. Beyond the current efforts to eradicate the last remaining wild polioviruses, global eradication efforts must safely navigate through an unprecedented series of endgame challenges to assure the permanent cessation of all human poliovirus infections.

  2. An Assessment of Poverty Eradication Programme (NAPEP in Nigeria

    Directory of Open Access Journals (Sweden)

    Adam Adem ANYEBE

    2015-06-01

    Full Text Available Poverty situation in Nigeria has become so serious that in 2013 there were as many as 112 million or 70.0% of the country’s population was living below poverty line. It has realized that poverty anywhere is a threat to peace, security and prosperity everywhere hence the conscious efforts by successive administrations in Nigeria to eradicate all forms of extreme poverty and hunger in a country. In spite of these efforts to eradicate absolute poverty in the country, poverty incidence has been on the rise. This study, therefore, attempted to assess NAPEP as a programme to eradicate extreme poverty in the country. Personal interviews and documents were employed in data collection. The data were analyzed using tables, simple percentages and spearman rank correlation. The study showed among others, that NAPEP as a programme targeted at eradicating extreme poverty has not been effective leading to a mixed bag of limited success and continuing challenges. It was therefore, recommended that the programme should be re-examined and possibly re-designed for effective performance instead of scrapping it.

  3. "Endgame" issues for the global polio eradication initiative.

    Science.gov (United States)

    2002-01-01

    The polio eradication initiative, created after the World Health Assembly resolved, in 1988, to eradicate poliomyelitis globally by 2000, has made remarkable progress. From 1988 through 2000, the number of countries where polio was endemic decreased from >125 to 20, and the estimated number of polio cases decreased from 350,000 to 99%. Wild-type 2 poliovirus has not been detected worldwide since October 1999, despite improving surveillance. The major focus of the eradication effort is to complete the task of stopping wild-type poliovirus transmission. Given the rapid progress made toward this goal, planning for the posteradication era has begun in earnest (1) to minimize the risk of reintroduction of virus into the population from laboratory stocks or long-term carriers, and (2) to prevent vaccine-derived polioviruses from circulating and causing outbreaks. This report summarizes the current thinking about these "endgame" issues, as put forth by the World Health Organization's technical advisory body for the initiative, the Technical Consultative Group on the Global Eradication of Poliomyelitis.

  4. When to declare successful eradication of an invasive predator?

    NARCIS (Netherlands)

    Rout, T.M.; Kirkwood, R.J.; Sutherland, D.R.; Murphy, S.; McCarthy, M.

    2014-01-01

    Imperfect detection methods make it difficult to tell whether an invasive species has been successfully eradicated. However, management cannot continue indefinitely when individuals are no longer detected – at some point, efforts must be reduced or ceased entirely. The risks of mistakenly inferring

  5. Polio eradication in the Netherlands: a proposal for surveillance

    NARCIS (Netherlands)

    van Loon AM; Rumke HC; Conyn-van Spaendonck MAE; CIE

    1998-01-01

    Voor de certificatie als polio-vrij in het kader van het wereld polio eradicatie programma is een actiever en uitgebreider surveillancesysteem vereist De 'Global Commission for the Certification of the Eradication of Poliomyelitis' en de Europese Commissie hebben de principes, criteria en

  6. Macroeconomics, (Adult) Education, and Poverty Eradication in Southern Africa

    Science.gov (United States)

    Nhamo, Senia; Nhamo, Godwell

    2006-01-01

    The Millennium Summit held in New York in September 2000 outlined the Millennium Development Goals (MDGs). The first of these involves the eradication of extreme poverty and hunger, setting two targets: halving by 2015 the percentage of the world's populace in 1990 with income less than US-$1 a day (i.e., cutting this percentage from 27.9 to 14%);…

  7. polio eradication in nigeria: — controversies and way forward.

    African Journals Online (AJOL)

    the WHO and the Federal Government after the result of the testing was released, ... and improved quality and coordination of vaccination -programme for Nigeria to ... survival, protection and development of children, ... Poliovirus from the world by the year 2002. ... eradication programme after the successful story of.

  8. A history of bovine tuberculosis eradication policy in Northern Ireland.

    Science.gov (United States)

    Robinson, P A

    2015-11-01

    Despite many years of state-sponsored efforts to eradicate the disease from cattle through testing and slaughter, bovine tuberculosis (bTB) is still regarded as the most important and complex of animal health challenges facing the British livestock agricultural industry. This paper provides a historical analysis of the ongoing bTB statutory eradication programme in one part of the UK - Northern Ireland (NI) - which began in 1949 as a voluntary scheme, but between 1959 and 1960 became compulsory for all cattle herd-owners. Tracing bTB back through time sets the eradication efforts of the present day within a deeper context, and provides signposts for what developed in subsequent decades. The findings are based primarily on empirical research using historical published reports of the Ministry of Agriculture and state documents held in the public archives in NI, and they emphasize the need to consider the economic, social and political contexts of disease eradication efforts and their influences on both the past and the present.

  9. [Eradication of Prototheca zopfii infection in a dairy cattle herd].

    Science.gov (United States)

    Rösler, U; Hensel, A

    2003-09-01

    Protothecosis is a severe form of mastitis in dairy cows caused by colorless algae of the genus Prototheca. Since P. zopfii is highly resistant to all known chemotherapeutics, infected cows must be removed from the herd. Eradication measures are difficult since many chronically infected cows may become intermittent shedders. Therefore, cultural methods are insufficient for control measures. In order to eradicate Prototheca zopfii-mastitis in dairy cattle herds, two isotype specific indirect ELISA for detection of IgA and IgG1 in whey were used in a dairy herd highly affected with protothecal mastitis. All cows (n = 313) were tested four times in intervals of six months. Milk specimens were examined in parallel by cultivation and serologically using two indirect ELISA systems for specific IgA and IgG1 in whey. Cows tested Prototheca positive were consequently separated from the herd and slaughtered. At the first examination, 15.6% of the animals were found positive by culture, and 23.3% were positive in at least one of the ELISA systems. Within two years, protothecal prevalence and incidence decreased to zero indicating that the eradication strategy used was successful. In summary, serological identification of P. zopfii-infected lactating cows is an useful tool to eradicate protothecal bovine mastitis in infected herds.

  10. The Efficacy of Sequential Therapy in Eradication of Helicobacter ...

    African Journals Online (AJOL)

    2017-05-22

    May 22, 2017 ... 2017 Nigerian Journal of Clinical Practice | Published by Wolters Kluwer - Medknow. Background and ... of the protocols. H. pylori eradication rate with sequential therapy in our patients ... steadily increasing, including gastric cancer prevention .... H. pylori in our country were levofloxacin based. A recent.

  11. Global polio eradication initiative: lessons learned and legacy.

    Science.gov (United States)

    Cochi, Stephen L; Freeman, Andrew; Guirguis, Sherine; Jafari, Hamid; Aylward, Bruce

    2014-11-01

    The world is on the verge of achieving global polio eradication. During >25 years of operations, the Global Polio Eradication Initiative (GPEI) has mobilized and trained millions of volunteers, social mobilizers, and health workers; accessed households untouched by other health initiatives; mapped and brought health interventions to chronically neglected and underserved communities; and established a standardized, real-time global surveillance and response capacity. It is important to document the lessons learned from polio eradication, especially because it is one of the largest ever global health initiatives. The health community has an obligation to ensure that these lessons and the knowledge generated are shared and contribute to real, sustained changes in our approach to global health. We have summarized what we believe are 10 leading lessons learned from the polio eradication initiative. We have the opportunity and obligation to build a better future by applying the lessons learned from GPEI and its infrastructure and unique functions to other global health priorities and initiatives. In so doing, we can extend the global public good gained by ending for all time one of the world's most devastating diseases by also ensuring that these investments provide public health dividends and benefits for years to come.

  12. Macroeconomics, (Adult) Education, and Poverty Eradication in Southern Africa

    Science.gov (United States)

    Nhamo, Senia; Nhamo, Godwell

    2006-01-01

    The Millennium Summit held in New York in September 2000 outlined the Millennium Development Goals (MDGs). The first of these involves the eradication of extreme poverty and hunger, setting two targets: halving by 2015 the percentage of the world's populace in 1990 with income less than US-$1 a day (i.e., cutting this percentage from 27.9 to 14%);…

  13. Scenarios for eradicating foot-and-mouth disease

    NARCIS (Netherlands)

    Bos, E.J.; Leeuwen, van M.G.A.; Vlieger, de J.J.

    2001-01-01

    Research project commissioned by the Ministery of Agriculture, Nature Management and Fisheries. With the help of desk-research and input-output analysis quantitative information is assembled about the differences in cost for agribusiness and tourism of two eradication scenarios for foot-and-mouth di

  14. The role of LP gas in eradicating energy poverty

    Energy Technology Data Exchange (ETDEWEB)

    Kelly, Michael; Behuria, Sarthak

    2010-09-15

    LP Gas is an ideal solution for dealing with energy poverty. Clean burning, low carbon, extremely efficient, requiring minimal infrastructure or R and D investment and with plentiful long term global supply, LP Gas can be quickly introduced to play an important role in eradicating energy poverty and steering both industrialised and developing countries onto more sustainable energy development paths.

  15. Archipelago-Wide Island Restoration in the Galápagos Islands: Reducing Costs of Invasive Mammal Eradication Programs and Reinvasion Risk

    OpenAIRE

    Victor Carrion; C. Josh Donlan; Karl J Campbell; Christian Lavoie; Felipe Cruz

    2011-01-01

    Invasive alien mammals are the major driver of biodiversity loss and ecosystem degradation on islands. Over the past three decades, invasive mammal eradication from islands has become one of society's most powerful tools for preventing extinction of insular endemics and restoring insular ecosystems. As practitioners tackle larger islands for restoration, three factors will heavily influence success and outcomes: the degree of local support, the ability to mitigate for non-target impacts, and ...

  16. Effect of Helicobacter pylori eradication on iron deficiency

    Institute of Scientific and Technical Information of China (English)

    ZHANG Zhi-feng; YANG Ning; ZHAO Gang; ZHU Lei; ZHU Ying; WANG Li-xia

    2010-01-01

    Background Iron deficiency (ID) is still a great challenge to health care worldwide. Results of randomized controlled trials (RCTs) evaluating the effect of Helicobacterpylori (H. Py/on) eradication on ID are contradictory. This study aimed to evaluate the effect of H. Pylori eradication on ID with a meta-analysis of RCTs. Methods Five electronic databases were searched for RCTs evaluating the effect of H. Pylori eradication on ID. Summary effects were assessed with the methods recommended by the Cochrane Collaboration. Results Eight studies involving 800 participants were included in this meta-analysis. The overall analysis showed that H. Pylori eradication accelerated the improvement of ferritin levels in ID people (mean difference (MD), 7.74 μg/L; 95% CI, 4.61 to 10.88; P <0.000 01). In a subgroup analysis, H. Pylori eradication accelerated the improvement of ferritin levels one month (MD, 7.00 pg/L; 95% CI, 1.72 to 12.28; P=0.009) and two months (MD, 9.80 μg/L; 95% CI, 2.22 to 17.40; P=0.01)after the initiation of treatment. However, H. Pylori eradication did not show a beneficial effect on the improvement of ferritin levels three months (MD, 7.20 pg/L; 95% CI, -3.25 to 17.65; P=0.18), one year (MD, 10.17 μg/L; 95% CI, -1.00 to 21.34;P=0.07) and forty months (MD, 1.00 pg/L; 95% CI, -0.57 to 2.57; P=0.21) after the initiation of treatment. H. Pylori eradication did not accelerate the improvement of hemoglobin concentrations in the overall analysis (MD, 0.38 g/dl; 95% CI,-0.45 to 1.22; P=0.37). In a subgroup analysis, H. Pylori eradication did not accelerate the improvement of hemoglobin concentrations one month (MD, -0.48 g/dl; 95% CI, -2.39 to 1.42; P=0.62), three months (MD, -0.10 g/dl; 95% CI, -0.35 to 0.15; P=0.44) and forty months (MD, 0.10 g/dl; 95% CI, -0.37 to 0.57; P=0.68) after the initiation of treatment. However, H. Pylori eradication accelerated the improvement of hemoglobin concentrations two months (MD, 1.96 g/dl; 95% CI, 1.48 to 2.44; P <0

  17. Role of humic substances in the degradation pathways and residual antibacterial activity during the photodecomposition of the antibiotic ciprofloxacin in water.

    Science.gov (United States)

    Porras, Jazmín; Bedoya, Cristina; Silva-Agredo, Javier; Santamaría, Alexander; Fernández, Jhon J; Torres-Palma, Ricardo A

    2016-05-01

    This study focuses on the photo-transformation, in presence of humic substances (HSs), of ciprofloxacin (CIP), a commonly-used fluoroquinolone antibiotic whose presence in aquatic ecosystems is a health hazard for humans and other living organisms. HSs from the International Humic Substances Society (Elliott humic acid and fulvic acid, Pahokee peat humic acid and Nordic lake) and a humic acid extracted from modified coal (HACM) were tested for their ability to photodegrade CIP. Based on kinetic and analytical studies, it was possible to establish an accelerating effect on the rate of CIP decomposition caused by the humic substances. This effect was associated with the photosensitized capacity of the HSs to facilitate energy transfer from an excited humic state to the ground state of ciprofloxacin. Except for Nordic lake, which experienced a lower positive effect, no significant differences in the CIP transformation were found among the different humic acids examined. The photochemistry of CIP can be modified by parameters such as pH, CIP or oxygen concentration. The irradiation of this antibiotic in the presence of HACM showed that antimicrobial activity was negligible after 14 h for E. coli and 24 h for S. aureus. In contrast, the antimicrobial activity was only slightly decreased after 24 h of irradiation by direct photolysis. Although mineralization of CIP irradiation in the presence of a HACM solution was not achieved, biodegradability was achieved after 12 h of irradiation, indicating that microorganisms within the environment can easily degrade CIP photochemical by-products. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Aerobic degradation of polychlorinated biphenyls

    Energy Technology Data Exchange (ETDEWEB)

    Pieper, D.H. [Dept. of Environmental Microbiology, German Research Center for Biotechnology, Braunschweig (Germany)

    2005-04-01

    The microbial degradation of polychlorinated biphenyls (PCBs) has been extensively studied in recent years. The genetic organization of biphenyl catabolic genes has been elucidated in various groups of microorganisms, their structures have been analyzed with respect to their evolutionary relationships, and new information on mobile elements has become available. Key enzymes, specifically biphenyl 2,3-dioxygenases, have been intensively characterized, structure/sequence relationships have been determined and enzymes optimized for PCB transformation. However, due to the complex metabolic network responsible for PCB degradation, optimizing degradation by single bacterial species is necessarily limited. As PCBs are usually not mineralized by biphenyl-degrading organisms, and cometabolism can result in the formation of toxic metabolites, the degradation of chlorobenzoates has received special attention. A broad set of bacterial strategies to degrade chlorobenzoates has recently been elucidated, including new pathways for the degradation of chlorocatechols as central intermediates of various chloroaromatic catabolic pathways. To optimize PCB degradation in the environment beyond these metabolic limitations, enhancing degradation in the rhizosphere has been suggested, in addition to the application of surfactants to overcome bioavailability barriers. However, further research is necessary to understand the complex interactions between soil/sediment, pollutant, surfactant and microorganisms in different environments. (orig.)

  19. Progress toward poliomyelitis eradication - Nigeria, January 2011-September 2012.

    Science.gov (United States)

    2012-11-09

    In 1988, the World Health Assembly launched the Global Polio Eradication Initiative (GPEI) and, in 2012, declared the completion of polio eradication a programmatic emergency for global public health. To date, wild poliovirus (WPV) cases reported worldwide in 2012 are at historically low levels. Nigeria is one of only three countries with uninterrupted WPV transmission (in addition to Pakistan and Afghanistan) and has been the origin of WPV imported into 25 previously polio-free countries since 2003. This report updates previous reports and describes polio eradication activities and progress in Nigeria during January 2011-September 2012, as of October 30, 2012. The number of reported WPV cases increased from 21 in 2010 to 62 in 2011. During January-September 2012, a total of 99 WPV cases were reported, more than doubling from the 42 cases reported during the same period in 2011. During 2011, a total of 32 circulating vaccine-derived polio virus type 2 (cVDPV2) cases were confirmed; six cVDPV2 cases were confirmed during January-September 2012, compared with 18 cVDPV2 cases during the same period in 2011. Nigeria's 2012 Polio Eradication Emergency Plan includes senior government leadership oversight, new program management and strategic initiatives, an accountability framework, and a surge in human resources to address chronically missed children during supplemental immunization activities (SIAs).* In 2012, indicators of immunization campaign quality show modest improvements; available data indicate gaps in surveillance. Continuing WPV transmission in Nigeria poses an ongoing risk for WPV reintroduction and outbreaks in polio-free countries and is a major obstacle to achieving global eradication.

  20. Post-polio eradication: vaccination strategies and options for India

    Directory of Open Access Journals (Sweden)

    Jayakrishnan Thayyil

    2014-11-01

    Full Text Available In 1988, the World Health Organization (WHO resolved to eradicate poliomyelitis globally. Since then, the initiative has reported dramatic progress in decreasing the incidence of poliomyelitis and limiting the geographical extent of transmission. 2013 is recorded as the second consecutive year not reporting wild poliovirus (WPV from India. If the country can retain this position for one more year India will be declared as polio eradicated. What should be the future vaccination strategies? We searched and reviewed the full text of the available published literature on polio eradication via PubMed and examined Internet sources and websites of major international health agencies. The oral polio vaccine (OPV has been the main tool in the polio eradication program. Once WPV transmission is interrupted, the poliomyelitis will be caused only by OPV. India could expect 1 vaccine-associated paralytic polio per 4.2-4.6 million doses of OPV. Considering the threat of vaccine-derived viruses to polio eradication, WHO urged to develop a strategy to safely discontinue OPV after certification. The ultimate aim is to stop OPV safely and effectively, and eventually substitute with inactivated polio vaccine (IPV. The argument against the use of IPV is its cost. From India, field based data were available on the efficacy of IPV, which was better than OPV. IPV given intradermally resulted in seroconversion rates similar to full-dose intramuscular vaccine. The incremental cost of adopting IPV to replace OPV is relatively low, about US $1 per child per year, and most countries should be able to afford this additional cost.

  1. Progress Toward Polio Eradication - Worldwide, 2015-2016.

    Science.gov (United States)

    Morales, Michelle; Tangermann, Rudolf H; Wassilak, Steven G F

    2016-05-13

    In 1988, the World Health Assembly resolved to eradicate poliomyelitis. Wild poliovirus (WPV) transmission persists in only two countries (Afghanistan and Pakistan) after the removal of Nigeria from the list of countries with endemic polio in September 2015.* Indigenous WPV type 2 has not been detected since 1999 and was declared eradicated by the Global Commission for the Certification of Poliomyelitis Eradication in September 2015.(†) Since November 2012, when the last case of WPV type 3 was detected in Nigeria, WPV type 1 has been the sole circulating type of WPV (1). This report summarizes global progress toward polio eradication during 2015-2016 and updates previous reports (2). In 2015, 74 WPV cases were reported in two countries (Afghanistan and Pakistan), a decrease of 79% from the 359 WPV cases reported in 2014 in nine countries; 12 WPV cases have been reported in 2016 (to date), compared with 23 during the same period in 2015 (3). Paralytic polio caused by circulating vaccine-derived poliovirus (cVDPV) remains a risk in areas with low oral poliovirus vaccine (OPV) coverage. Seven countries, including Pakistan, reported 32 cVDPV cases in 2015 (4). In four of these countries, ≥6 months have passed since the most recent case or isolate. One country (Laos) with VDPV transmission in 2015 has reported three additional cVDPV cases in 2016 to date. Encouraging progress toward polio eradication has been made over the last year; however, interruption of WPV transmission will require focus on reaching and vaccinating every missed child through high quality supplementary immunization activities (SIAs) and cross-border coordination between Afghanistan and Pakistan (5,6).

  2. Metabolic consequences of Helicobacter pylori infection and eradication.

    Science.gov (United States)

    Buzás, György Miklós

    2014-05-14

    Helicobacter pylori (H. pylori) is still the most prevalent infection of the world. Colonization of the stomach by this agent will invariably induce chronic gastritis which is a low-grade inflammatory state leading to local complications (peptic ulcer, gastric cancer, lymphoma) and remote manifestations. While H. pylori does not enter circulation, these extragastric manifestations are probably mediated by the cytokines and acute phase proteins produced by the inflammed mucosa. The epidemiologic link between the H. pylori infection and metabolic changes is inconstant and controversial. Growth delay was described mainly in low-income regions with high prevalence of the infection, where probably other nutritional and social factors contribute to it. The timely eradication of the infection will lead to a more healthy development of the young population, along with preventing peptic ulcers and gastric cancer An increase of total, low density lipoprotein and high density liporote