2,135 research outputs found
Building microbial factories for the production of aromatic amino acid pathway derivatives: From commodity chemicals to plant-sourced natural products
No full textThe aromatic amino acid biosynthesis pathway, together with its downstream branches, represents one of the most commercially valuable biosynthetic pathways, producing a diverse range of complex molecules with many useful bioactive properties. Aromatic compounds are crucial components for major commercial segments, from polymers to foods, nutraceuticals, and pharmaceuticals, and the demand for such products has been projected to continue to increase at national and global levels. Compared to direct plant extraction and chemical synthesis, microbial production holds promise not only for much shorter cultivation periods and robustly higher yields, but also for enabling further derivatization to improve compound efficacy by tailoring new enzymatic steps. This review summarizes the biosynthetic pathways for a large repertoire of commercially valuable products that are derived from the aromatic amino acid biosynthesis pathway, and it highlights both generic strategies and specific solutions to overcome certain unique problems to enhance the productivities of microbial hosts.This is a manuscript of an article published as Cao, Mingfeng, Meirong Gao, Miguel Suastegui, Yanzhen Mei, and Zengyi Shao. "Building microbial factories for the production of aromatic amino acid pathway derivatives: From commodity chemicals to plant-sourced natural products." Metabolic Engineering (2019). DOI: 10.1016/j.ymben.2019.08.008. </p
Investigating the role of noncoding regulatory DNA in plasmid development for Yarrowia lipolytica
No full textProduction of industrially relevant compounds in microbial cell factories can employ either genomes or plasmids as an expression platform. Selection of plasmids as pathway carriers is advantageous for rapid demonstration but poses a challenge of stability. Yarrowia lipolytica has attracted great attention in the past decade for the biosynthesis of chemicals related to fatty acids at titers attractive to industry, and many genetic tools have been developed to explore its oleaginous potential. Our recent studies on the autonomously replicating sequences (ARSs) of nonconventional yeasts revealed that the ARSs fromY. lipolytica showcase a unique structure that includes a previously unannotated sequence (spacer) linking the origin of replication (ORI) and the centromeric (CEN) element and plays a critical role in modulating plasmid behavior. Maintaining a native 645-bp spacer yielded a 4.5-fold increase in gene expression and higher plasmid stability compared to a more universally employed minimized ARS. Testing the modularity of the ARS sub-elements indicated that plasmid stability exhibits a pronounced cargo dependency. Instability caused both plasmid loss and intramolecular rearrangements. Altogether, our work clarifies the appropriate application of various ARSs for the scientific community and sheds light on a previously unexplored DNA element as a potential target for engineering Y. lipolytica.This is a pre-print of the article Lopez, Carmen, Mingfeng Cao, Zhanyi Yao, and Zengyi Shao. Investigating the role of noncoding regulatory DNA in plasmid development for Yarrowia lipolytica. Authorea (2020). DOI: 10.22541/au.160691063.38058320/v1. Posted with permission.</p
The world's largest macroalgal bloom in the Yellow Sea, China Formation and implications.pdf
No full textPlants and soil are the base for sustainably surviving human beings on the globe as the role of materials, energy, resources and environment (Shao & Chu 2008; Shao et al. 2008, 2009, 2010, 2012a,b; Liu & Shao, 2010; Ruan et al. 2010; Xu et al. 2010, 2012; Shao 2012; Huang et al. 2013). This topic has been extensively investigated for 100 years with more achievements in many sectors and practical significance in conducting high-efficient agriculture and eco-environmental construction. The plant-soil interaction is the core issue of this topic, which has been given much attention for the past 30 years (Wu et al. 2007, 2010; Zhang et al. 2011, 2013; Xu et al. 2012, 2013).Plants and soil are the base for sustainably surviving human beings on the globe as the role of materials, energy, resources and environment (Shao & Chu 2008; Shao et al. 2008, 2009, 2010, 2012a,b; Liu & Shao, 2010; Ruan et al. 2010; Xu et al. 2010, 2012; Shao 2012; Huang et al. 2013). This topic has been extensively investigated for 100 years with more achievements in many sectors and practical significance in conducting high-efficient agriculture and eco-environmental construction. The plant-soil interaction is the core issue of this topic, which has been given much attention for the past 30 years (Wu et al. 2007, 2010; Zhang et al. 2011, 2013; Xu et al. 2012, 2013)
The Houses of Duke Chou and Duke Shao : Some Questions Concerning the Origin of the Book of Shao Kao
No full textNot enough has been clarified about the origin of the early part of the Shu Ching. In this respect, what needs be determined first may be the relationship between Duke Chou 周公 and Duke Shao 召公, the two principal characters in those books. The two dukes, who used to be considered brothers or kinsmen, have been established by recent researches as the representatives of two tribes that had earlier been subject to the Yin but cooperated with the Chou at the time of the latter’s overthrow of the Yin at the end of the eleventh century B. C. The Shao, in particular, joined the Chou camp out of fear that a part of its territory might be confiscated by the Yin.The earliest part of the Shu Ching seems to be based upon the theme of the antagonism between Duke Chou and Duke Shao. Firstly, after the death of King Wu 武王, his younger brother Duke Chou succeeded to the throne as the former’s son King Ch’eng 成王 was still a minor, thus incurring ill feeling of the Chou Clansmen and the tribal chieftains who had supported the Chou. Secondly, the city of Lo i 洛邑, that was built for governing the East after the suppression of the Easterners which had taken place after the death of King Wu, was situated within the sphere of influence of Duke Shao. We learn from the Shu Ching and the bronze inscriptions that Duke Shao, who was younger than Duke Chou by more than thirty years, could never contend with the latter on an equal footing as long as the latter was alive. Duke Chou abdicated after seven years in favor of King Ch’eng and died after a little over three years thereafter. This changed the situation for Duke Shao. The earlier books of the Shu Ching, the Lo Kao 洛誥 and the likes, seldom refer to Duke Shao and ascribe the establishment and government of Lo i to Duke Chou, while such books as the Shao Kao 召誥 and the Chün Shih 君奭 say that the same city was built by nobody but Duke Shao and that his government was entrusted by King Ch’eng. The present order of the books in the Shu Ching, which predates the Shao Kao to the Lo Kao, is due to still later editing.The present author reconstructs, from the bronze inscriptions, the process in which Duke Shao, after the death of Duke Chou, deported the latter’s descendants to faraway places and took over the control of Lo i. He concludes that the two books, Shao Kao and Chün Shih, were written to justify Duke Shao’s sway over that city.journal articl
Revisiting the unique structure of autonomously replicating sequences in Yarrowia lipolytica and its role in pathway engineering
No full textProduction of industrially relevant compounds in microbial cell factories can employ either genomes or plasmids as an expression platform. Selection of plasmids as pathway carriers is advantageous for rapid demonstration but poses a challenge of stability. Yarrowia lipolytica has attracted great attention in the past decade for the biosynthesis of chemicals related to fatty acids at titers attractive to industry, and many genetic tools have been developed to explore its oleaginous potential. Our recent studies on the autonomously replicating sequences (ARSs) of nonconventional yeasts revealed that the ARSs from Y. lipolytica showcase a unique structure that includes a previously unannotated sequence (spacer) linking the origin of replication (ORI) and the centromeric (CEN) element and plays a critical role in modulating plasmid behavior. Maintaining a native 645-bp spacer yielded a 2.2-fold increase in gene expression and 1.7-fold higher plasmid stability compared to a more universally employed minimized ARS. Testing the modularity of the ARS sub-elements indicated that plasmid stability exhibits a pronounced cargo dependency. Instability caused both plasmid loss and intramolecular rearrangements. Altogether, our work clarifies the appropriate application of various ARSs for the scientific community and sheds light on
a previously unexplored DNA element as a potential target for engineering Y. lipolytica.This is a manuscript of an article published as Lopez, Carmen, Mingfeng Cao, Zhanyi Yao, and Zengyi Shao. "Revisiting the unique structure of autonomously replicating sequences in Yarrowia lipolytica and its role in pathway engineering." Applied Microbiology and Biotechnology 105, no. 14 (2021): 5959-5972. doi: https://doi.org/10.1007/s00253-021-11399-4
Protective effects on myocardial infarction model: delivery of schisandrin B using matrix metalloproteinase-sensitive peptide-modified, PEGylated lipid nanoparticles
No full textMingfeng Shao,1 Wenfang Yang,2 Guangying Han1 1Department of Cardiology, Linyi People’s Hospital, Linyi, Shandong, People’s Republic of China; 2Department of Internal Medicine, Linyi Hot Spring Hospital of Shandong Coal Mine, Linyi, Shandong, People’s Republic of China Purpose: Schisandrin B (Sch B) is clinically applied for the treatment of hepatitis and ischemic disease. However, its clinical efficacy is limited due to the poor solubility and low bioavailability. This study aimed to develop matrix metalloproteinase (MMP)-sensitive peptide-modified, polyethylene glycol (PEG)-modified (PEGylated) solid lipid nanoparticles (SLNs) for loading Sch B (MMP-Sch B SLNs), and to evaluate the therapeutic effect in the myocardial infarction model.Methods: PEG lipid and MMP-targeting peptide conjugate were synthesized. MMP-Sch B SLNs were prepared by solvent displacement technique. The physicochemical properties and pharmacokinetics of SLNs were investigated. In vivo effects on infarct size was evaluated in rats.Results: The successful synthesis of lipid-peptide conjugate was confirmed. MMP-Sch B SLNs had a particle size of 130 nm, a zeta potential of 18.3 mV, and a sustained-release behavior. Higher heart drug concentration and longer blood circulation times were achieved by Sch B loaded SLNs than the drug solution according to the pharmacokinetic and biodistribution results. The best therapeutic efficacy was exhibited by MMP-Sch B SLNs by reducing the infarction size to the greatest extent.Conclusion: The modified SLNs may be a good choice for delivery of Sch B for the treatment of myocardial infarction. Keywords: cardiovascular diseases, CVDs, schisandrin B, matrix metalloproteinase, lipid nanoparticle
Third Place Design: Reconnect historic social-spatial network of Shao City, Chengdu, China
No full textThe general problem of the thesis project is the issue of declining liveability of old neighbourhood area and the lost place identity of Shao City. To be more specific, the problem focus is the fractured social-spatial network between the old neighbourhood and the area for new social class like Kuanzhai Alley & gated communities with declining third place for local residents. The abandoned historical buildings,crowed courtyard space occupied by the informal constructions & car park and Kuanzhai Alley full of tourists and commercial activities reduce the third place of the neighbourhood and decrease its liveability and identity. The spatial gaps in Shao City have been formed. Meanwhile, the social condition in the neighbourhood is degrading. The social class is lowering in the old neighbourhood due to the rise of Kuanzhai Alley as many original residents could not stand the tourists. The upgrading of the social class in gated communities and the inaccessible public space in the new social class area caused the social segregation between the old social class and higher social in this area. From the heritage perspective, it is crucial to reconnect the social-spatial network with rich third place in Shao City for new identity. From residents’ perspective, the complete social-spatial network with good third place is important for improving the liveability.Architecture, Urbanism and Building Science
Role of the mismatch repair gene, Msh6, in suppressing genome instability
No full textMismatch repair (MMR) is critical for preserving genomic integrity. Failure of this system can accelerate somatic mutation and increase the risk of developing cancer. MSH6, in complex with MSH2, is the MMR protein that mediates DNA repair through the recognition of 1- and 2-bp mismatches. To evaluate the effects of MSH6 deficiency on genomic stability we compared the frequency of in vivo loss of heterozygosity (LOH) between MSH6-proficient and deficient, 129S2 x C57BL/6 F1 hybrid mice that were heterozygous for our reporter gene Aprt. We recovered mutant cells that had functionally lost APRT protein activity and categorized the spectrum of mutations responsible for the LOH events. We also measured the mutant frequency at the X-linked gene, Hprt, as a second reporter for point mutation. In Msh6-/-Aprt+/- mice, mutation frequency at Aprt was elevated in both T cells and fibroblasts by 2.5-fold and 5.7-fold, respectively, over Msh6+/+Aprt+/- littermate controls. While a modest increase in mitotic recombination (MR) was observed in MSH6-deficient fibroblasts compared to wild type controls, point mutation was the predominant mechanism leading to APRT deficiency in both cell types. Base substitution, consisting of multiple types of transitions, accounted for all of the point mutations identified within the Aprt coding region. We also assessed the role of MSH6 in preventing mutations caused by a common environmental mutagen, ionizing radiation (IR). In Msh6-/-Aprt+/- mice, 4 Gy of X-irradiation induced a significant increase in point mutations at both Aprt and Hprt in T cells, but not in fibroblasts. These findings indicate that MutSα reduces spontaneous and IR-induced mutation in a cell-type dependant manner.The publisher's final edited version is available at http://www.sciencedirect.com/science/journal/0027510
Aspects of Metaphysics and Cosmology in Shao Yong’s Philosophy of Numbers
No full textBakalaura darba tēma „Metafizikas un kosmoloģijas aspekti Šao Jun skaitļu filozofijā” veltīta filozofa, dzejnieka un kosmologa un vienai no konfuciānisma atjaunošanas nozīmīgākajām personībām, Šao Jun (1011-1077) filozofijas izpētei. Darba mērķis ir izpētīt metafizikas un kosmoloģijas aspektus Šao Jun filozofijā. Šao Jun skaitļu filozofija ir balstīta uz „Pārmaiņu kanonu”, tāpēc darbā apskatīta „Pārmaiņu kanona” izcelsme, tiek noteikta Šao Jun vieta un loma neokonfuciānisma tradīcijā, kā arī izpētīta Šao Jun filozofija un viņa „Pārmaiņu kanona” interpretācija.
Darbā gaitā analizēta arī budisma un daoisma ietekme uz Šao Jun skaitļu filozofiju, jo pētnieku vidū viņš uzskatīts par netradicionāli domājošu neokonfuciānistu, izpētīta Džu Sji kritika, kas vērsta pret Šao Jun, apskatīti filozofijas pamatelementi un galvenie filozofiskie darbi, kuros paustas šīs idejas.
Bakalaura darbs sastāv no divām daļām. Darba pirmā daļa veltīta kosmoloģijas izpētei neokonfuciānisma tradīcijā un „Pārmaiņu kanonam”, kas neokonfuciānisma tradīcijā tika izcelts starp pārējiem konfuciānisma klasiskajiem tekstiem. Otrā daļa veltīta Šao Jun personības un skaitļu filozofijas izpētei, veidojot saikni ar pirmajā nodaļā pētīto „Pārmaiņu kanonu” un aprakstīts, kā viņa izveidotās kosmoloģiskās diagrammas vairākus gadsimtus vēlāk interpretējis vācu matemātiķis Gotfrīds Vilhelms Leibnics.
Darba apjoms ir 45 lpp.The title of this thesis is „Aspects of Metaphysics and Cosmology in Shao Yong’s Philosophy of Numbers”, and it is devoted to research a philosophy of philosopher, poet, cosmologist and one of the most significant figures in process of Confucianism revival, Shao Yong (1011-1077). The aim of this work is to research aspects of metaphysics and cosmology in Shao Yong’s philosophy. Shao Yong’s philosophy of numbers is based on the „Book of Changes”, therefore author in her work describes the origins of the „Book of Changes”, also defines Shao Yong’s place and role in tradition of Neo-confucianism and researches Shao Yong’s interpretation of the „Book of Changes”.
During the research it was analized how Buddhism and Daoism have influenced Shao Yong’s philosophy of numbers, because he is considered as an orthodox Neo-confucianist among researchers, also it was found out why Shao Yong was criticized by Zhu Xi and examined the key elements of Shao Yong’s philosophy and the main philosophical works, where these key elements are mentioned.
The work consists of two parts. The first part is devoted to research cosmology in tradition of Neo-confucianism and the „Book of Changes”, because during the Song dynasty „Book of Changes” was emphasized amongst other Confucian classics, especially by Shao Yong. The second part is devoted to analyse personality of Shao Yong and he’s philosophy, linking it with the „Book of Changes”, as researched in the first part, and describing how the cosmological charts of Shao Yong’s was interpreted by German mathematician Gottfried Wilhelm Leibniz several centuries later.
The total amount of the work is 45 pages
Les diagrammes de Shao Yong (1012-1077). Qui les a vus ?
No full textAlain Arrault : Shao Yong's Diagrams. Who saw them ?
It is commonly admitted that Shao Yong (1012-1077) is the author, among others, of the very famous Square and Circular Diagrams of the Sixty-four Hexagrams (Liushisi gua fang yuan tu). The most reliable editions of his cosmological work do not, however, include any of these "written images." We shall therefore track very closely the heirs and commentators who have contributed to shape this tradition, among whom Zhu Xi (1130-1200) stands out most prominently. This way the encounter with a barely known preface by Shao Yong will convey us to a very different diagram, the Diagram of the Adjustment of Mutations by the Supreme Mystery (Taixuan zhun Yi tu), putting thereby the Taixuan jing, whose author is Yang Xiong (53 B.C.-1 8 A.D.), at the core of the Northern Song Confucian renewal. Beyond, or beneath, the issue of authenticity and editorial history, we shall also, implicitely though, question the nature and function of the scholarly diagram, an image that oscillates between sacralization and desacralization, between text and abstract figure, where the concept of vision, of which the Chinese philosophy is said to be devoid, comes to full play.Il est généralement admis que Shao Yong est l'auteur, entre autres, des très célèbres Diagrammes carré et circulaire des soixante-quatre hexagrammes (Liushisi gua fang yuan tu). Les éditions de son œuvre cosmologique les plus fiables ne comportent pourtant aucune de ces «images écrites ». Nous suivrons donc pas à pas les héritiers et commentateurs, parmi lesquels figure Zhu Xi (1 130-1 200), qui ont contribué à la formation de cette tradition. Chemin faisant, la rencontre d'une préface de Shao Yong quasiment ignorée nous conduira vers un tout autre diagramme, le Diagramme de l'ajustement des Mutations par le Mystère suprême (Taixuan zhun Yi tu), remettant ainsi au cœur du renouveau confucéen des Song du Nord le Taixuan jing de Yang Xiong (53 av. J.-C.-18 ap. J.-C.). Au delà, ou en deçà, du problème de l'authenticité et de l'histoire éditoriale, il s'agira également de s'interroger, en filigrane, sur la nature et la fonction du diagramme lettré, une image oscillant entre désacralisation et sacralisation, entre texte et graphisme abstrait, où la vertu de la vision, que l'on dit absente de la philosophie chinoise, prend toute son ampleurArrault Alain. Les diagrammes de Shao Yong (1012-1077). Qui les a vus ?. In: Études chinoises, vol. 19, n°1-2, Printemps-Automne 2000. Mélanges de sinologie offerts à Jean-Pierre Diény ( II) pp. 67-114
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