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61.
M Ozkan SG Desai Y Zhang DM Stevenson J Beane EA White ML Guerinot LR Lynd 《Journal of industrial microbiology & biotechnology》2001,27(5):275-280
Characteristics of 13 newly isolated thermophilic, anaerobic, and cellulolytic strains were compared with previously described
strains of Clostridium thermocellum: ATCC 27405 and JW20 (ATCC 31549). Colony morphology, antibiotic sensitivity, fermentation end-products, and cellulose degradation
were documented. All 13 strains were sensitive to erythromycin (5 μg/ml) and chloramphenicol (25 μg/ml), and all strains but
one were sensitive to kanamycin (20 μg/ml). Polymerase chain reaction (PCR) amplification using primers based on gene sequences
from C. thermocellum ATCC 27405 was successful for all 13 strains in the case of the hydrogenase gene and 11 strains in the case of phosphotransacetylase/acetate
kinase genes. Ten strains amplified a product of the expected size with primers developed to be specific for C. thermocellum 16SrRNA primers. Two of the 13 strains did not amplify any product with the PCR primers designed for the phosphotransacetylase/acetate
kinase and 16SrRNA primers. A MboI-like GATC- recognizing restriction activity was present in all of the five strains examined. The results of this study have
several positive implications with respect to future development of a transformation system for cellulolytic thermophiles.
Journal of Industrial Microbiology & Biotechnology (2001) 27, 275–280.
Received 12 September 2000/ Accepted in revised form 20 November 2000 相似文献
62.
HI-NESS: a family of genetically encoded DNA labels based on a bacterial nucleoid-associated protein
Fatema-Zahra M Rashid Eike Mahlandt Michiel van
der
Vaart Daphne E C Boer Monica Varela
Alvarez Bram Henneman Daan J W Brocken Patrick Voskamp Anneloes
J Blok Thomas
S Shimizu Annemarie
H Meijer Martijn
S Luijsterburg Joachim Goedhart Frdric G E Crmazy Remus
T Dame 《Nucleic acids research》2022,50(2):e10
63.
64.
Iris E. Glykofridis Alex A. Henneman Jesper A. Balk Richard Goeij-de Haas Denise Westland Sander R. Piersma Jaco C. Knol Thang V. Pham Michiel Boekhout Fried J.T. Zwartkruis Rob M.F. Wolthuis Connie R. Jimenez 《Molecular & cellular proteomics : MCP》2022,21(9):100263
In Birt–Hogg–Dubé (BHD) syndrome, germline loss-of-function mutations in the Folliculin (FLCN) gene lead to an increased risk of renal cancer. To address how FLCN inactivation affects cellular kinase signaling pathways, we analyzed comprehensive phosphoproteomic profiles of FLCNPOS and FLCNNEG human renal tubular epithelial cells (RPTEC/TERT1). In total, 15,744 phosphorylated peptides were identified from 4329 phosphorylated proteins. INKA analysis revealed that FLCN loss alters the activity of numerous kinases, including tyrosine kinases EGFR, MET, and the Ephrin receptor subfamily (EPHA2 and EPHB1), as well their downstream targets MAPK1/3. Validation experiments in the BHD renal tumor cell line UOK257 confirmed that FLCN loss contributes to enhanced MAPK1/3 and downstream RPS6K1/3 signaling. The clinically available MAPK inhibitor Ulixertinib showed enhanced toxicity in FLCNNEG cells. Interestingly, FLCN inactivation induced the phosphorylation of PIK3CD (Tyr524) without altering the phosphorylation of canonical Akt1/Akt2/mTOR/EIF4EBP1 phosphosites. Also, we identified that FLCN inactivation resulted in dephosphorylation of TFEB Ser109, Ser114, and Ser122, which may be linked to increased oxidative stress levels in FLCNNEG cells. Together, our study highlights differential phosphorylation of specific kinases and substrates in FLCNNEG renal cells. This provides insight into BHD-associated renal tumorigenesis and may point to several novel candidates for targeted therapies. 相似文献
65.
Patch-clamp recording of charge movement, Ca(2+) current, and Ca(2+) transients in adult skeletal muscle fibers 总被引:1,自引:0,他引:1
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Intramembrane charge movement (Q), Ca(2+) conductance (G(m)) through the dihydropyridine-sensitive L-type Ca(2+) channel (DHPR) and intracellular Ca(2+) fluorescence (F) have been recorded simultaneously in flexor digitorum brevis muscle fibers of adult mice, using the whole-cell configuration of the patch-clamp technique. The voltage distribution of Q was fitted to a Boltzmann equation; the Q(max), V(1/2Q), and effective valence (z(Q)) values were 41 +/- 3.1 nC/&mgr;F, -17.6 +/- 0.7 mV, and 2.0 +/- 0.12, respectively. V(1/2G) and z(G) values were -0.3 +/- 0.06 mV and 5.6 +/- 0.34, respectively. Peak Ca(2+) transients did not change significantly after 30 min of recording. F was fit to a Boltzmann equation, and the values for V(F1/2) and z(F) were 6.2 +/- 0.04 mV and 2.4, respectively. F was adequately fit to the fourth power of Q. These results demonstrate that the patch-clamp technique is appropriate for recording Q, G(m), and intracellular [Ca(2+)] simultaneously in mature skeletal muscle fibers and that the voltage distribution of the changes in intracellular Ca(2+) can be predicted by a Hodgkin-Huxley model. 相似文献
66.
Feyz L. Nannan Panday R. Henneman M. Verzijlbergen F. Constantinescu A. A. van Dalen B. M. Brugts J. J. Caliskan K. Geleijnse M. L. Kardys I. Van Mieghem N. M. Manintveld O. Daemen J. 《Netherlands heart journal》2022,30(3):149-159
Netherlands Heart Journal - The aim of the present study was to assess the safety and efficacy of renal sympathetic denervation (RDN) in patients with heart failure with reduced ejection fraction... 相似文献
67.
Ay?e Demirkan Peter Henneman Aswin Verhoeven Harish Dharuri Najaf Amin Jan Bert van Klinken Lennart C. Karssen Boukje de Vries Axel Meissner Sibel G?raler Arn M. J. M. van den Maagdenberg André M. Deelder Peter A. C ’t Hoen Cornelia M. van Duijn Ko Willems van Dijk 《PLoS genetics》2015,11(1)
Metabolite quantitative traits carry great promise for epidemiological studies, and their genetic background has been addressed using Genome-Wide Association Studies (GWAS). Thus far, the role of less common variants has not been exhaustively studied. Here, we set out a GWAS for metabolite quantitative traits in serum, followed by exome sequence analysis to zoom in on putative causal variants in the associated genes. 1H Nuclear Magnetic Resonance (1H-NMR) spectroscopy experiments yielded successful quantification of 42 unique metabolites in 2,482 individuals from The Erasmus Rucphen Family (ERF) study. Heritability of metabolites were estimated by SOLAR. GWAS was performed by linear mixed models, using HapMap imputations. Based on physical vicinity and pathway analyses, candidate genes were screened for coding region variation using exome sequence data. Heritability estimates for metabolites ranged between 10% and 52%. GWAS replicated three known loci in the metabolome wide significance: CPS1 with glycine (P-value = 1.27×10−32), PRODH with proline (P-value = 1.11×10−19), SLC16A9 with carnitine level (P-value = 4.81×10−14) and uncovered a novel association between DMGDH and dimethyl-glycine (P-value = 1.65×10−19) level. In addition, we found three novel, suggestively significant loci: TNP1 with pyruvate (P-value = 1.26×10−8), KCNJ16 with 3-hydroxybutyrate (P-value = 1.65×10−8) and 2p12 locus with valine (P-value = 3.49×10−8). Exome sequence analysis identified potentially causal coding and regulatory variants located in the genes CPS1, KCNJ2 and PRODH, and revealed allelic heterogeneity for CPS1 and PRODH. Combined GWAS and exome analyses of metabolites detected by high-resolution 1H-NMR is a robust approach to uncover metabolite quantitative trait loci (mQTL), and the likely causative variants in these loci. It is anticipated that insight in the genetics of intermediate phenotypes will provide additional insight into the genetics of complex traits. 相似文献
68.
We present BioGraph, a data integration and data mining platform for the exploration and discovery of biomedical information.
The platform offers prioritizations of putative disease genes, supported by functional hypotheses. We show that BioGraph can
retrospectively confirm recently discovered disease genes and identify potential susceptibility genes, outperforming existing
technologies, without requiring prior domain knowledge. Additionally, BioGraph allows for generic biomedical applications
beyond gene discovery. BioGraph is accessible at . 相似文献
69.
The isoprenoid biosynthesis pathway provides the cell with a variety of compounds which are involved in multiple cellular processes. Inhibition of this pathway with statins and bisphosphonates is widely applied in the treatment of hypercholesterolemia and metabolic bone disease, respectively. In addition, since isoprenylation of proteins is an important therapeutic target in cancer research there is interest in interfering with isoprenoid biosynthesis, for which new inhibitors to block farnesylation and geranylgeranylation of small GTPases are being developed. We recently developed a sensitive method using UPLC-MS/MS that allows the direct detection and quantification of all intermediates of the mevalonate pathway from MVA to GGPP which can be used to verify the specificity of inhibitors of the isoprenoid biosynthesis pathway. We here investigated the specificity of several inhibitors of the isoprenoid biosynthesis pathway in HepG2 cells, fibroblasts and lymphoblasts. The nitrogen-containing bisphosphonates pamidronate and zoledronate specifically inhibit farnesyl pyrophosphate synthase indicated by the accumulation of IPP/DMAPP. However, zaragozic acid A, a squalene synthase inhibitor, causes an increase of MVA in addition to the expected increase of FPP. Analysis of isoprenoid intermediate profiles after incubation with 6-fluoromevalonate showed a very nonspecific result with an increase in MVA, MVAP, MVAPP and IPP/DMAPP. These results show that inhibitors of a particular enzyme of the isoprenoid biosynthesis pathway can have additional effects on other enzymes of the pathway either direct or indirect through accumulation of isoprenoid intermediates. Our method can be used to test new inhibitors and their effect on overall isoprenoid biosynthesis. 相似文献