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81.
Daniel J. Saltzberg Shruthi Viswanath Ignacia Echeverria Ilan E. Chemmama Ben Webb Andrej Sali 《Protein science : a publication of the Protein Society》2021,30(1):250-261
Biology is advanced by producing structural models of biological systems, such as protein complexes. Some systems are recalcitrant to traditional structure determination methods. In such cases, it may still be possible to produce useful models by integrative structure determination that depends on simultaneous use of multiple types of data. An ensemble of models that are sufficiently consistent with the data is produced by a structural sampling method guided by a data‐dependent scoring function. The variation in the ensemble of models quantified the uncertainty of the structure, generally resulting from the uncertainty in the input information and actual structural heterogeneity in the samples used to produce the data. Here, we describe how to generate, assess, and interpret ensembles of integrative structural models using our open source Integrative Modeling Platform program ( https://integrativemodeling.org ). 相似文献
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旗舰物种是保护生物学中一个广泛应用的概念, 用于获得公众对保护行为的支持, 在生物多样性保护领域发挥着重要作用。但目前尚未见量化分析遴选和确定旗舰物种的公开报道, 致使学术界对旗舰物种的定义和使用相对主观, 缺乏科学依据。本文对旗舰物种的定义进行了梳理, 探讨了旗舰物种的内涵, 确定了旗舰物种的属性, 制定了遴选标准和量化遴选方法, 以便读者更好地理解和运用这一概念。目前旗舰物种的定义仍然局限在其社会学属性, 作者建议今后应加强其生物生态学属性。作者认为除了公众的关注度和认可度之外, 旗舰物种还应具备以下3个生态生物学和社会文化特征: (1)物种在当地的濒危程度及生存现状; (2)物种在当地生态系统中的重要性; (3)物种在当地民众中的影响力和认可度。基于此, 本文确定了表征旗舰物种社会文化属性和生态生物学属性的8个要素, 基于层次分析法提出了一种量化的旗舰物种遴选方法。该方法综合上述8个要素进行评判和计算分值, 以塔吉克斯坦境内分布的14种大型濒危哺乳动物的生态生物学属性和社会文化影响力为基础, 描述基于层次分析法遴选塔吉克斯坦哺乳类旗舰物种的方法和过程, 最终依据每个备选物种所得分值高低排序, 得到塔吉克斯坦旗舰物种的优先备选物种。本文首次提出了一种量化遴选旗舰物种的方法, 期望今后可基于该方法开发更加合理的旗舰物种遴选模型和算法。 相似文献
84.
Adaptive laboratory evolution and reverse engineering enhances autotrophic growth in Pichia pastoris
Synthetic biology offers several routes for CO2 conversion into biomass or bio-chemicals, helping to avoid unsustainable use of organic feedstocks, which negatively contribute to climate change. The use of well-known industrial organisms, such as the methylotrophic yeast Pichia pastoris (Komagataella phaffii), for the establishment of novel C1-based bioproduction platforms could wean biotechnology from feedstocks with alternative use in food production. Recently, the central carbon metabolism of P. pastoris was re-wired following a rational engineering approach, allowing the resulting strains to grow autotrophically with a μmax of 0.008 h−1, which was further improved to 0.018 h−1 by adaptive laboratory evolution. Using reverse genetic engineering of single-nucleotide (SNPs) polymorphisms occurring in the genes encoding for phosphoribulokinase and nicotinic acid mononucleotide adenylyltransferase after evolution, we verified their influence on the improved autotrophic phenotypes. The reverse engineered SNPs lead to lower enzyme activities in putative branching point reactions and in reactions involved in energy balancing. Beyond this, we show how further evolution facilitates peroxisomal import and increases growth under autotrophic conditions. The engineered P. pastoris strains are a basis for the development of a platform technology, which uses CO2 for production of value-added products, such as cellular biomass, technical enzymes and chemicals and which further avoids consumption of organic feedstocks with alternative use in food production. Further, the identification and verification of three pivotal steps may facilitate the integration of heterologous CBB cycles or similar pathways into heterotrophic organisms. 相似文献
85.
David B. Sattelle Sarah C. R. Lummis James F. H. Wong James J. Rauh 《Neurochemical research》1991,16(3):363-374
A GABA-operated Cl– channel that is bicuculline-insensitive is abundant in the nervous tissue of cockroach, in housefly head preparations and thorax/abdomen preparations, and in similar preparations from several insect species. Bicuculline-insensitive GABA-operated Cl– channels, which are rare in vertebrates, possess sites of action of benzodiazepines, steroids and insecticides that are pharmacologically-distinct from corresponding sites on vertebrate GABAA receptors. The pharmacological profile of the benzodiazepine-binding site linked to an insect CNS GABA-operated Cl– channel resembles more closely that of vertebrate peripheral benzodiazepine-binding sites. Six pregnane steroids and certain polychlorocycloalkane insecticides, which are active att-butylbicy-clophosphorothionate (TBPS)-binding sites, also differ in their effectiveness on vertebrate and insect GABA receptors. Radioligand binding and physiological studies indicate that in insects there may be subtypes of the GABA receptor. Molecular biology offers experimental approaches to understanding the basis of this diversity.Special issue dedicated to Dr. Eugene Roberts 相似文献
86.
The methylerythritol phosphate (MEP) pathway of Plasmodium falciparum (P. falciparum) has become an attractive target for anti-malarial drug discovery. This study describes a kinetic model of this pathway, its use in validating 1-deoxy-d-xylulose 5-phosphate reductoisomerase (DXR) as drug target from the systemic perspective, and additional target identification, using metabolic control analysis and in silico inhibition studies. In addition to DXR, 1-deoxy-d-xylulose 5-phosphate synthase (DXS) can be targeted because it is the first enzyme of the pathway and has the highest flux control coefficient followed by that of DXR. In silico inhibition of both enzymes caused large decrement in the pathway flux. An added advantage of targeting DXS is its influence on vitamin B1 and B6 biosynthesis. Two more potential targets, 2-C-methyl-d-erythritol 2,4-cyclodiphosphate synthase and 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate synthase, were also identified. Their inhibition caused large accumulation of their substrates causing instability of the system. 相似文献
87.
Coupling recent advancements in genetic engineering of diverse microbes and gas-driven fermentation provides a path towards sustainable commodity chemical production. Cupriavidus necator H16 is a suitable species for this task because it effectively utilizes H2 and CO2 and is genetically tractable. Here, we demonstrate the versatility of C. necator for chemical production by engineering it to produce three products from CO2 under lithotrophic conditions: sucrose, polyhydroxyalkanoates (PHAs), and lipochitooligosaccharides (LCOs). We engineered sucrose production in a co-culture system with heterotrophic growth 30 times that of WT C. necator. We engineered PHA production (20–60% DCW) and selectively altered product composition by combining different thioesterases and phaCs to produce copolymers directly from CO2. And, we engineered C. necator to convert CO2 into the LCO, a plant growth enhancer, with titers of ~1.4 mg/L—equivalent to yields in its native source, Bradyrhizobium. We applied the LCOs to germinating seeds as well as corn plants and observed increases in a variety of growth parameters. Taken together, these results expand our understanding of how a gas-utilizing bacteria can promote sustainable production. 相似文献
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89.
A. Kleczkowski C. A. Gilligan D. J. Bailey 《Proceedings. Biological sciences / The Royal Society》1997,264(1384):979-984
Components of transmission for primary infection from soil-borne inoculum and secondary (plant to plant) infection are estimated from experiments involving single plants. The results from these individual-based experiments are used in a probabilistic spatial contact process (cellular automaton) to predict the progress of an epidemic. The model accounts for spatial correlations between infected and susceptible plants due to inhomogeneous mixing caused by restricted movement of the pathogen in soil. It also integrates nonlinearities in infection, including small stochastic differences in primary infection that become amplified by secondary infection. The model predicts both the mean and the variance of the infection dynamics of R. solani when compared with replicated epidemics in populations of plants grown in microcosms. The broader consequences of the combination of experimental and modelling approaches for scaling-up from individual to population behaviour are discussed. <br> 相似文献
90.