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| 1 | Activation of microbial secondary metabolic pathways:Avenues and challenges显示文摘Microbial natural products are a tremendous source of new bioactive chemical entities for drug discovery.Next generation sequencing has revealed an unprecedented genomic potential for production of secondary metabolites by diverse micro-organisms found in the environment and in the microbiota.Genome mining has further led to the discovery of numerous uncharacterized‘cryptic’metabolic pathways in the classical producers of natural products such as Actinobacteria and fungi.These biosynthetic gene clusters may code for improved biologically active metabolites,but harnessing the full genetic potential has been hindered by the observation that many of the pathways are‘silent’under laboratory conditions.Here we provide an overview of the various biotechnological methodologies,which can be divided to pleiotropic,biosynthetic gene cluster specific,and targeted genome-wide approaches that have been developed for the awakening of microbial secondary metabolic pathways. | Bikash Baral Amir Akhgari Mikko Metsä-Ketelä | 2018 | Synthetic and Systems Biotechnology2018，3，3： | 4 |
| 2 | Frequent mutations of the CA simple sequence repeat in intron 1 of EGFR in mismatch repair-deficient colorectal cancers显示文摘AIM:To investigate the polymorphic simple sequencerepeat in intron 1 of the epidermal growth factor receptorgene(EGFR)(CA-SSRⅠ),which is known to affect theefficiency of gene transcription as a putative target of themismatch repair(MMR)machinery in colorectal tumors.METHODS:The CA-SSRⅠgenotype was analyzed ina total of 86 primary colorectal tumors,selected upontheir microsatellite instability(MSI)status[42 with highfrequency MSI(MSI-H)and 44 microsatellite stable(MSS)]and their respective normal tissue.The effect of the CA-SSRⅠgenotype on the expression of the EGFR gene wasevaluated in 18 specimens using quantitative real-timereverse transcription PCR and immunohistochemistry.RESULTS:Mutations in CA-SSRⅠwere detected in 86%(36 of 42)of MSI-H colorectal tumors and 0%(0 of 44)ofMSS tumors,indicating the EGFR gene as a novel putativespecific target of the defective MMR system(P<0.001).Impaired expression of EGFR was detected in most ofthe colorectal tumors analyzed[6/12(50%)at the mRNAlevel and 15/18(83%)at the peptide level].However,noassociation was apparent between EGFR expression andCA-SSRⅠstatus in tumors or normal tissues.CONCLUSION:Our results suggest that CA-SSRⅠsequence does not contribute to the regulation of EGFRtranscription in colon,and should thus not be consideredas a promising predictive marker for response to EGFRinhibitors in patients with colorectal cancer. | Marie-Pierre Buisine Agnès Wacrenier Christophe Mariette Emmanuelle Leteurtre Fabienne Escande Sana Aissi Amandine Ketele Annette Leclercq Nicole Porchet Thécla Lesuffleur | 2008 | World Journal of Gastroenterology2008，14，7： | 3 |
| 3 | Clinical significance of small-intestinal microsporidiosis in HIV-1-infected individuals 显示文摘 | Eeftinck Schattenkerk JK van Gool T van Ketel RJ | 1991 | Lancet1991，337，8746： | 1 |
| 4 | Conventional,conformal,an d intensity modulated radiat ion therapy treatment planning of external beam radiotherapy f or cervical cancer:the impact of tumor regression显示文摘 | BUNT L HEIDE UA KETEL AARS M | | 0，，： | 1 |
| 5 | Survival and morphology of auditory neurons in dissociated cultures of newborn mouse spiral ganglion 显示文摘 | Whitlon DS Ketels KV Coulson MT | 2006 | J Neurosci2006，138，： | 1 |
| 6 | Coma in a child after treatment with the'magic salve'lidocaine-prilocaine cream显示文摘 | Wieringa JW Ketel AG van Houten MA | 2006 | Nederlands Tijdschrift Voor Geneeskunde2006，150，1： | 1 |
| 7 | Oral ascorbic acid increases plasma oestradiol during postmenopausal hormone replacement therapy显示文摘 | Tarja Vihtam?ki Jouko Parantainen Anna-Maija Koivisto Timo Mets?-Ketel? Risto Tuimala | 2002 | Maturitas2002，，2： | 1 |
| 8 | Detection of Haemophilus influenzae in cerebrospinal fluids by polymerase chain reaction DNA amplification显示文摘 | Van Ketel RJ De Wever B Van Alphen L | 1990 | J Med Microbiol1990，33，4： | 1 |
| 9 | Effect of ratio of unsat- urated to saturated fatty acids of the dietary lipid frac- tion on utilization and metabolizable energy of added fats in young chicks 显示文摘 | KETELS E DE GROOTE G | 1989 | Poultry Science1989，68，11： | 1 |
| 10 | Competitive advantage and the value network configuration显示文摘 | Fjeldstad Φ D and Ketels C H M | 2006 | Long Range Planning2006，39，2： | 1 |
| 11 | Nonculture detection of Haemophilus influenzae in sputum with monoclonal antibodies specific for outer membrane lipoprotein P6 显示文摘 | Groeneveld K van Alphen L van Ketel R J | 1989 | J C/in Microbiol1989，27，10： | 1 |
| 12 | Survival and morphology of auditory neurons in dissociated cultures of newborn mouse spiral ganglion 显示文摘 | WHITLON D S KETELS K V COULSON M T | 2006 | Neuroscience2006，138，： | 1 |
| 13 | Competitiveness in Developing Economics:The Roles of Clusters and Cross-Cutting Policies显示文摘 | Ketels Christian | 2006 | Workshop Held in Bagamoyo TZ2006，，： | 1 |
| 14 | Successful management of a nonmalignant esophageal perforation with a coated stent显示文摘 | Mumtaz H Barone GW Ketel BL | 2002 | Ann Thorac Surg2002，74，： | 1 |
| 15 | Optical pumping system design for large production of hyperpolarized 129Xe显示文摘 | Ruset IC Ketel S Hersman FW | 2006 | Phys Rev Lett2006，96，05： | 1 |
| 16 | Detection of enterotoxigenic Escherichia coli in stool samples by using nonradioactively labeled oligonucleotide DNA probes and PCR显示文摘 | Pool G J van Ketel R | 1994 | J Clin Microbiol1994，32，： | 1 |
| 17 | Detection of enterotoxigenie escherichia coli in stool samples by using non radioactively labeled oligo-nucleotide DNA probes and PCR显示文摘 | Schuhsz C Pool G J Van ketel R | 1994 | Clin Microbiol1994，32，： | 1 |
| 18 | Industrial policy in the United States显示文摘 | KETELS C | 2007 | Jour-nal of Industry Competition and Trade2007，7，3： | 1 |
| 19 | Obese but not normalweight women with polycystic ovary syndrome are characterized by metabolic and microvascular insulin resistance显示文摘 | Ketel IJ Stehouwer CD Serne EH | 2008 | J Clin Endocrinol Metab2008，93，9： | 1 |
| 20 | Michael Porter's Competitive Framework : Recent Learnings and New Research Priorities 显示文摘 | Ketels C | 2006 | Journal of Industrial Trade and Competitive2006，，6： | 1 |
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