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371.
Haigis KM Kendall KR Wang Y Cheung A Haigis MC Glickman JN Niwa-Kawakita M Sweet-Cordero A Sebolt-Leopold J Shannon KM Settleman J Giovannini M Jacks T 《Nature genetics》2008,40(5):600-608
Kras is commonly mutated in colon cancers, but mutations in Nras are rare. We have used genetically engineered mice to determine whether and how these related oncogenes regulate homeostasis and tumorigenesis in the colon. Expression of K-Ras(G12D) in the colonic epithelium stimulated hyperproliferation in a Mek-dependent manner. N-Ras(G12D) did not alter the growth properties of the epithelium, but was able to confer resistance to apoptosis. In the context of an Apc-mutant colonic tumor, activation of K-Ras led to defects in terminal differentiation and expansion of putative stem cells within the tumor epithelium. This K-Ras tumor phenotype was associated with attenuated signaling through the MAPK pathway, and human colon cancer cells expressing mutant K-Ras were hypersensitive to inhibition of Raf, but not Mek. These studies demonstrate clear phenotypic differences between mutant Kras and Nras, and suggest that the oncogenic phenotype of mutant K-Ras might be mediated by noncanonical signaling through Ras effector pathways. 相似文献
372.
Cristine Margaret R. Atienza 《Systemic Practice and Action Research》2017,30(6):569-592
This paper features the implementation of an extensive insider action research, exhaustively following the framework of Coghlan and Brannick (2010, 2014). It consisted of two action research projects - the thesis action research and the core action research - which were done in a parallel manner, both following the iterative cycles of constructing, planning, taking, and evaluating action. The thesis action research was aimed at developing a theory on building organizational identity from the viewpoint of an organizational founder. On the other hand, the core action research was focused on promoting the specific identity of the Institute for Integrality, Inc. Quality and rigor were observed in the implementation of the action research cycles. In the fieldwork, there were three main cycles undertaken – understanding organizational identity, fine-tuning the practice of this identity, and designing the integration of this identity in organizational culture. Thereafter, significant learnings were derived from meta-learning in the form of content, process, and premise reflections. Finally, through the critical reflection of the project in the light of the experience and theory, A-Founder’s Integrative Theory of Organizational Identity Building was derived. 相似文献
373.
S. Lecompte M. Abou-Samra R. Boursereau L. Noel S. M. Brichard 《Cellular and molecular life sciences : CMLS》2017,74(13):2487-2501
Background
Persistent inflammation exacerbates the progression of Duchenne muscular dystrophy (DMD). The hormone, adiponectin (ApN), which is decreased in the metabolic syndrome, exhibits anti-inflammatory properties on skeletal muscle and alleviates the dystrophic phenotype of mdx mice. Here, we investigate whether ApN retains its anti-inflammatory action in myotubes obtained from DMD patients. We unravel the underlying mechanisms by studying the secretome and the early events of ApN.Methods
Primary cultures of myotubes from DMD and control patients were treated or not by ApN after an inflammatory challenge. Myokines secreted in medium were identified by cytokine antibody-arrays and ELISAs. The early events of ApN signaling were assessed by abrogating selected genes.Results
ApN retained its anti-inflammatory properties in both dystrophic and control myotubes. Profiling of secretory products revealed that ApN downregulated the secretion of two pro-inflammatory factors (TNFα and IL-17A), one soluble receptor (sTNFRII), and one chemokine (CCL28) in DMD myotubes, while upregulating IL-6 that exerts some anti-inflammatory effects. These changes were explained by pretranslational mechanisms. Earlier events of the ApN cascade involved AdipoR1, the main receptor for muscle, and the AMPK-SIRT1-PGC-1α axis leading, besides alteration of the myokine profile, to the upregulation of utrophin A (a dystrophin analog).Conclusion
ApN retains its beneficial properties in dystrophic muscles by activating the AdipoR1-AMPK-SIRT1-PGC-1α pathway, thereby inducing a shift in the secretion of downstream myokines toward a less inflammatory profile while upregulating utrophin. ApN, the early events of the cascade and downstream myokines may be therapeutic targets for the management of DMD.374.
375.
Diego Reginensi Patricia Carulla Sara Nocentini Oscar Seira Abel Torres-Espín Andreu Matamoros-Angles Rosalina Gavín María Teresa Moreno-Flores Francisco Wandosell Josep Samitier Xavier Trepat Xavier Navarro José Antonio del Río 《Cellular and molecular life sciences : CMLS》2015,72(14):2719-2737
Olfactory ensheathing cell (OEC) transplantation emerged some years ago as a promising therapeutic strategy to repair injured spinal cord. However, inhibitory molecules are present for long periods of time in lesioned spinal cord, inhibiting both OEC migration and axonal regrowth. Two families of these molecules, chondroitin sulphate proteoglycans (CSPG) and myelin-derived inhibitors (MAIs), are able to trigger inhibitory responses in lesioned axons. Mounting evidence suggests that OEC migration is inhibited by myelin. Here we demonstrate that OEC migration is largely inhibited by CSPGs and that inhibition can be overcome by the bacterial enzyme Chondroitinase ABC. In parallel, we have generated a stable OEC cell line overexpressing the Nogo receptor (NgR) ectodomain to reduce MAI-associated inhibition in vitro and in vivo. Results indicate that engineered cells migrate longer distances than unmodified OECs over myelin or oligodendrocyte-myelin glycoprotein (OMgp)-coated substrates. In addition, they also show improved migration in lesioned spinal cord. Our results provide new insights toward the improvement of the mechanisms of action and optimization of OEC-based cell therapy for spinal cord lesion. 相似文献
376.
Stephen R. Goldberg Charles R. Bursey L. Lee Grismer 《Journal of Natural History》2015,49(43-44):2683-2691
A total of 12 species of Cnemaspis (N = 104) from Southeast Asia were examined for gastrointestinal helminths. Samples consisted of nine species (n = 86) from Peninsular Malaysia: Cnemaspis affinis (n = 4); Cnemaspis baueri (n = 17); Cnemaspis biocellata (n = 12); Cnemaspis grismeri (n = 8); Cnemaspis kumpoli (n = 11); Cnemaspis limi (n = 9): Cnemaspis monachorum (n = 7); Cnemaspis pemanggilensis (n = 10); Cnemaspis peninsularis (n = 8); one species (n = 5) from Cambodia and Thailand, Cnemaspis chanthaburiensis (n = 5); and two species (n = 13) from Vietnam: Cnemaspis nuicamensis (n = 6) and Cnemaspis tucdupensis (n = 7). The aggregate helminth community consisted of one species of Cestoda, Cylindrotaenia malayi and nine species of Nematoda: Bakeria schadi, Meteterakis singaporensis, Parapharyngodon maplestoni, Maxvachonia sp., Physalopteroides sp., Physalopteridae gen. sp., Riticulariidae gen. sp., Seuratoidea gen. sp., Ascaridoidea gen. sp. Meteterakis singaporensis had the largest number of individuals (457) and greatest prevalence (24%). Twenty-eight new host records are reported. 相似文献
377.
A remarkable new eucoiline genus and species, Muhaka icipe, is described herein. The genus is clearly a Kleidotomini, but is distinguished from other genera in the tribe by a unique head and scutellar morphology. The genus belongs to the ‘wedge-head’-syndrome group of species that, to date, is unique to Afrotropical eucoilines. The new genus and species is reminiscent of Stentorceps Quinlan and Nanocthulhu Buffington, but is readily distinguished from these genera. Muhaka was collected from a threatened kaya (sacred forest) of coastal Kenya. The biological importance of this and other kaya forests, as well as their protection, is discussed.http://www.zoobank.org/urn:lsid:zoobank.org:pub:6918ED2C-69A4-48FC-A1E4-2B5DFF58E876 相似文献
378.
Morelli G Song Y Mazzoni CJ Eppinger M Roumagnac P Wagner DM Feldkamp M Kusecek B Vogler AJ Li Y Cui Y Thomson NR Jombart T Leblois R Lichtner P Rahalison L Petersen JM Balloux F Keim P Wirth T Ravel J Yang R Carniel E Achtman M 《Nature genetics》2010,42(12):1140-1143
Plague is a pandemic human invasive disease caused by the bacterial agent Yersinia pestis. We here report a comparison of 17 whole genomes of Y. pestis isolates from global sources. We also screened a global collection of 286 Y. pestis isolates for 933 SNPs using Sequenom MassArray SNP typing. We conducted phylogenetic analyses on this sequence variation dataset, assigned isolates to populations based on maximum parsimony and, from these results, made inferences regarding historical transmission routes. Our phylogenetic analysis suggests that Y. pestis evolved in or near China and spread through multiple radiations to Europe, South America, Africa and Southeast Asia, leading to country-specific lineages that can be traced by lineage-specific SNPs. All 626 current isolates from the United States reflect one radiation, and 82 isolates from Madagascar represent a second radiation. Subsequent local microevolution of Y. pestis is marked by sequential, geographically specific SNPs. 相似文献
379.
The developmental dynamics of the maize leaf transcriptome 总被引:5,自引:0,他引:5
380.
Triosephosphate isomerase: a highly evolved biocatalyst 总被引:1,自引:0,他引:1
R. K. Wierenga E. G. Kapetaniou R. Venkatesan 《Cellular and molecular life sciences : CMLS》2010,67(23):3961-3982
Triosephosphate isomerase (TIM) is a perfectly evolved enzyme which very fast interconverts dihydroxyacetone phosphate and d-glyceraldehyde-3-phosphate. Its catalytic site is at the dimer interface, but the four catalytic residues, Asn11, Lys13, His95 and Glu167, are from the same subunit. Glu167 is the catalytic base. An important feature of the TIM active site is the concerted closure of loop-6 and loop-7 on ligand binding, shielding the catalytic site from bulk solvent. The buried active site stabilises the enediolate intermediate. The catalytic residue Glu167 is at the beginning of loop-6. On closure of loop-6, the Glu167 carboxylate moiety moves approximately 2 Å to the substrate. The dynamic properties of the Glu167 side chain in the enzyme substrate complex are a key feature of the proton shuttling mechanism. Two proton shuttling mechanisms, the classical and the criss-cross mechanism, are responsible for the interconversion of the substrates of this enolising enzyme. 相似文献