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181.
Essential isoprenoid compounds are synthesized using the 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway in many gram-negative bacteria, some gram-positive bacteria, some apicomplexan parasites, and plant chloroplasts. The alternative mevalonate pathway is found in archaea and eukaryotes, including cytosolic biosynthesis in plants. The existence of orthogonal essential pathways in eukaryotes and bacteria makes the MEP pathway an attractive target for the development of antimicrobial agents. A system is described for identifying mutations in the MEP pathway of Salmonella enterica serovar Typhimurium. Using this system, point mutations induced by diethyl sulfate were found in the all genes of the essential MEP pathway and also in genes involved in uptake of methylerythritol. Curiously, none of the MEP pathway genes could be identified in the same parent strain by transposon mutagenesis, despite extensive searches. The results complement the biochemical and bioinformatic approaches to the elucidation of the genes involved in the MEP pathway and also identify key residues for activity in the enzymes of the pathway. 相似文献
182.
Heat shock induces chromosome loss in the yeast Candida albicans 总被引:5,自引:0,他引:5
Craig Hilton David Markie Brain Corner Erik Rikkerink Russel Poulter 《Molecular & general genetics : MGG》1985,200(1):162-168
Summary The heat shock protocol described in this paper causes mitotic instability in log phase Candida albicans cells. Such instability is induced in diploid, aneuploid and tetraploid strains. The strains analysed are multiple heterozygotes which facilitates the detection of mitotic instability as manifested by the formation of homozygotes. Strains previously shows to be carrying cis linked mutant alleles show coincident segregation of the linked alleles. Conversely, strains which carry unlinked mutant alleles display no such coincident segregation. This segregation of complete linkage groups suggests that heat shock is inducing chromosome some loss in C. albicans. The application of this protocol to the genetics of the imperfect fungus C. albicans has produced evidence of at least three chromosomes. 相似文献
183.
Gerlt JA Allen KN Almo SC Armstrong RN Babbitt PC Cronan JE Dunaway-Mariano D Imker HJ Jacobson MP Minor W Poulter CD Raushel FM Sali A Shoichet BK Sweedler JV 《Biochemistry》2011,50(46):9950-9962
The Enzyme Function Initiative (EFI) was recently established to address the challenge of assigning reliable functions to enzymes discovered in bacterial genome projects; in this Current Topic, we review the structure and operations of the EFI. The EFI includes the Superfamily/Genome, Protein, Structure, Computation, and Data/Dissemination Cores that provide the infrastructure for reliably predicting the in vitro functions of unknown enzymes. The initial targets for functional assignment are selected from five functionally diverse superfamilies (amidohydrolase, enolase, glutathione transferase, haloalkanoic acid dehalogenase, and isoprenoid synthase), with five superfamily specific Bridging Projects experimentally testing the predicted in vitro enzymatic activities. The EFI also includes the Microbiology Core that evaluates the in vivo context of in vitro enzymatic functions and confirms the functional predictions of the EFI. The deliverables of the EFI to the scientific community include (1) development of a large-scale, multidisciplinary sequence/structure-based strategy for functional assignment of unknown enzymes discovered in genome projects (target selection, protein production, structure determination, computation, experimental enzymology, microbiology, and structure-based annotation), (2) dissemination of the strategy to the community via publications, collaborations, workshops, and symposia, (3) computational and bioinformatic tools for using the strategy, (4) provision of experimental protocols and/or reagents for enzyme production and characterization, and (5) dissemination of data via the EFI's Website, http://enzymefunction.org. The realization of multidisciplinary strategies for functional assignment will begin to define the full metabolic diversity that exists in nature and will impact basic biochemical and evolutionary understanding, as well as a wide range of applications of central importance to industrial, medicinal, and pharmaceutical efforts. 相似文献
184.
PILL Collaborative Group Rodgers A Patel A Berwanger O Bots M Grimm R Grobbee DE Jackson R Neal B Neaton J Poulter N Rafter N Raju PK Reddy S Thom S Vander Hoorn S Webster R 《PloS one》2011,6(5):e19857
Background
There has been widespread interest in the potential of combination cardiovascular medications containing aspirin and agents to lower blood pressure and cholesterol (‘polypills’) to reduce cardiovascular disease. However, no reliable placebo-controlled data are available on both efficacy and tolerability.Methods
We conducted a randomised, double-blind placebo-controlled trial of a polypill (containing aspirin 75 mg, lisinopril 10 mg, hydrochlorothiazide 12.5 mg and simvastatin 20 mg) in 378 individuals without an indication for any component of the polypill, but who had an estimated 5-year cardiovascular disease risk over 7.5%. The primary outcomes were systolic blood pressure (SBP), LDL-cholesterol and tolerability (proportion discontinued randomised therapy) at 12 weeks follow-up.Findings
At baseline, mean BP was 134/81 mmHg and mean LDL-cholesterol was 3.7 mmol/L. Over 12 weeks, polypill treatment reduced SBP by 9.9 (95% CI: 7.7 to 12.1) mmHg and LDL-cholesterol by 0.8 (95% CI 0.6 to 0.9) mmol/L. The discontinuation rates in the polypill group compared to placebo were 23% vs 18% (RR 1.33, 95% CI 0.89 to 2.00, p = 0.2). There was an excess of side effects known to the component medicines (58% vs 42%, p = 0.001), which was mostly apparent within a few weeks, and usually did not warrant cessation of trial treatment.Conclusions
This polypill achieved sizeable reductions in SBP and LDL-cholesterol but caused side effects in about 1 in 6 people. The halving in predicted cardiovascular risk is moderately lower than previous estimates and the side effect rate is moderately higher. Nonetheless, substantial net benefits would be expected among patients at high risk.Trial Registration
Australian New Zealand Clinical Trials Registry ACTRN12607000099426 相似文献185.
Yue He Shushi Peng Yongwen Liu Xiangyi Li Kai Wang Philippe Ciais M. Altaf Arain Yuanyuan Fang Joshua B. Fisher Daniel Goll Daniel Hayes Deborah N. Huntzinger Akihiko Ito Atul K. Jain Ivan A. Janssens Jiafu Mao Campioli Matteo Anna M. Michalak Changhui Peng Josep Peuelas Benjamin Poulter Dahe Qin Daniel M. Ricciuto Kevin Schaefer Christopher R. Schwalm Xiaoying Shi Hanqin Tian Sara Vicca Yaxing Wei Ning Zeng Qiuan Zhu 《Global Change Biology》2020,26(3):1474-1484
Plants use only a fraction of their photosynthetically derived carbon for biomass production (BP). The biomass production efficiency (BPE), defined as the ratio of BP to photosynthesis, and its variation across and within vegetation types is poorly understood, which hinders our capacity to accurately estimate carbon turnover times and carbon sinks. Here, we present a new global estimation of BPE obtained by combining field measurements from 113 sites with 14 carbon cycle models. Our best estimate of global BPE is 0.41 ± 0.05, excluding cropland. The largest BPE is found in boreal forests (0.48 ± 0.06) and the lowest in tropical forests (0.40 ± 0.04). Carbon cycle models overestimate BPE, although models with carbon–nitrogen interactions tend to be more realistic. Using observation‐based estimates of global photosynthesis, we quantify the global BP of non‐cropland ecosystems of 41 ± 6 Pg C/year. This flux is less than net primary production as it does not contain carbon allocated to symbionts, used for exudates or volatile carbon compound emissions to the atmosphere. Our study reveals a positive bias of 24 ± 11% in the model‐estimated BP (10 of 14 models). When correcting models for this bias while leaving modeled carbon turnover times unchanged, we found that the global ecosystem carbon storage change during the last century is decreased by 67% (or 58 Pg C). 相似文献
186.
Zhen Zhang Flurin Babst Valentin Bellassen David Frank Thomas Launois Kun Tan Philippe Ciais Benjamin Poulter 《Ecosystems》2018,21(3):410-425
The impacts of climate variability and trends on European forests are unevenly distributed across different bioclimatic zones and species. Extreme climate events are also becoming more frequent and it is unknown how they will affect feedbacks of CO2 between forest ecosystems and the atmosphere. An improved understanding of species differences at the regional scale of the response of forest productivity to climate variation and extremes is thus important for forecasting forest dynamics. In this study, we evaluate the climate sensitivity of aboveground net primary production (NPP) simulated by two dynamic global vegetation models (DGVM; ORCHIDEE and LPJ-wsl) against tree ring width (TRW) observations from about 1000 sites distributed across Europe. In both the model simulations and the TRW observations, forests in northern Europe and the Alps respond positively to warmer spring and summer temperature, and their overall temperature sensitivity is larger than that of the soil-moisture-limited forests in central Europe and Mediterranean regions. Compared with TRW observations, simulated NPP from ORCHIDEE and LPJ-wsl appear to be overly-sensitive to climatic factors. Our results indicate that the models lack biological processes that control time lags, such as carbohydrate storage and remobilization, that delay the effects of radial growth dynamics to climate. Our study highlights the need for re-evaluating the physiological controls on the climate sensitivity of NPP simulated by DGVMs. In particular, DGVMs could be further enhanced by a more detailed representation of carbon reserves and allocation that control year-to-year variation in plant growth. 相似文献
187.
Mengtian Huang Shilong Piao Yan Sun Philippe Ciais Lei Cheng Jiafu Mao Ben Poulter Xiaoying Shi Zhenzhong Zeng Yingping Wang 《Global Change Biology》2015,21(6):2366-2378
Defined as the ratio between gross primary productivity (GPP) and evapotranspiration (ET), ecosystem‐scale water‐use efficiency (EWUE) is an indicator of the adjustment of vegetation photosynthesis to water loss. The processes controlling EWUE are complex and reflect both a slow evolution of plants and plant communities as well as fast adjustments of ecosystem functioning to changes of limiting resources. In this study, we investigated EWUE trends from 1982 to 2008 using data‐driven models derived from satellite observations and process‐oriented carbon cycle models. Our findings suggest positive EWUE trends of 0.0056, 0.0007 and 0.0001 g C m?2 mm?1 yr?1 under the single effect of rising CO2 (‘CO2’), climate change (‘CLIM’) and nitrogen deposition (‘NDEP’), respectively. Global patterns of EWUE trends under different scenarios suggest that (i) EWUE‐CO2 shows global increases, (ii) EWUE‐CLIM increases in mainly high latitudes and decreases at middle and low latitudes, (iii) EWUE‐NDEP displays slight increasing trends except in west Siberia, eastern Europe, parts of North America and central Amazonia. The data‐driven MTE model, however, shows a slight decline of EWUE during the same period (?0.0005 g C m?2 mm?1 yr?1), which differs from process‐model (0.0064 g C m?2 mm?1 yr?1) simulations with all drivers taken into account. We attribute this discrepancy to the fact that the nonmodeled physiological effects of elevated CO2 reducing stomatal conductance and transpiration (TR) in the MTE model. Partial correlation analysis between EWUE and climate drivers shows similar responses to climatic variables with the data‐driven model and the process‐oriented models across different ecosystems. Change in water‐use efficiency defined from transpiration‐based WUEt (GPP/TR) and inherent water‐use efficiency (IWUEt, GPP×VPD/TR) in response to rising CO2, climate change, and nitrogen deposition are also discussed. Our analyses will facilitate mechanistic understanding of the carbon–water interactions over terrestrial ecosystems under global change. 相似文献
188.
Type II isopentenyl diphosphate (IPP) isomerase catalyzes the interconversion of IPP and dimethylallyl diphosphate (DMAPP). Although the reactions catalyzed by the type II enzyme and the well-studied type I IPP isomerase are identical, the type II protein requires reduced flavin for activity. The chemical mechanism, including the role of flavin, has not been established for type II IPP isomerase. Recombinant type II IPP isomerase from Thermus thermophilus HB27 was purified by Ni2+ affinity chromatography. The aerobically purified enzyme was inactive until the flavin cofactor was reduced by NADPH or dithionite or photochemically. The inactive oxidized flavin-enzyme complex bound IPP in a Mg2+-dependent manner for which KD approximately KmIPP, suggesting that the substrate binds to the inactive oxidized and active reduced forms of the protein with similar affinities. N,N-Dimethyl-2-amino-1-ethyl diphosphate (NIPP), a transition state analogue for the type I isomerase, competitively inhibits the type II enzyme, but with a much lower affinity. pH-dependent spectral changes indicate that the binding of IPP, DMAPP, and a saturated analogue isopentyl diphosphate promotes protonation of anionic reduced flavin. Electron paramagnetic resonance (EPR) and UV-visible spectroscopy show a substrate-dependent accumulation of the neutral flavin semiquinone during both the flavoenzyme reduction and reoxidation processes in the presence of IPP and related analogues. Redox potentials of IPP-bound enzyme indicate that the neutral semiquinone state of the flavin is stabilized thermodynamically relative to free FMN in solution. 相似文献
189.
190.
Tazeen H. Jafar Imtiaz Jehan Feng Liang Sylvaine Barbier Muhammad Islam Rasool Bux Aamir Hameed Khan Nivedita Nadkarni Neil Poulter Nish Chaturvedi Shah Ebrahim 《PloS one》2015,10(11)