195 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
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
Mechanistic insight into the interaction of gastrointestinal mucus with oral diblock copolymers synthesized via ATRP method
No full textJiao Liu,1,* Jie Cao,1,* Jianhua Cao,2 Shangcong Han,1 Yan Liang,1 Mingfeng Bai,3 Yong Sun1 1Department of Pharmaceutics, School of Pharmacy, Qingdao University, Qingdao, China; 2Department of Pharmacy, Qingdao No 3 Hospital, Qingdao, China; 3Department of Radiology and Radiological Sciences, Institute of Imaging Sciences, Vanderbilt University Medical Center, Nashville, TN, USA *These authors contributed equally to this work Introduction: Nanoparticles are increasingly used as drug carriers for oral administration. The delivery of drug molecules is largely dependent on the interaction of nanocarriers and gastrointestinal (GI) mucus, a critical barrier that regulates drug absorption. It is therefore important to understand the effects of physical and chemical properties of nanocarriers on the interaction with GI mucus. Unfortunately, most of the nanoparticles are unable to be prepared with satisfactory structural monodispersity to comprehensively investigate the interaction. With controlled size, shape, and surface chemistry, copolymers are ideal candidates for such purpose. Materials and methods: We synthesized a series of diblock copolymers via the atom transfer radical polymerization method and investigated the GI mucus permeability in vitro and in vivo. Results: Our results indicated that uncharged and hydrophobic copolymers exhibited enhanced GI absorption. Conclusion: These results provide insights into developing optimal nanocarriers for oral administration. Keywords: absorption barriers, oral drug delivery system, ATRP, nanoparticle
Search For Electrophysiological Biomarkers Of Arousal In Anesthesia And After Cardiac Arrest
No full textElectrophysiological recordings, notably Electroencephalography (EEG) and Somatosensory Evoked Potentials (SSEP) play pivotal roles in clinical settings, offering insights into the functioning of the nervous system and aiding in diagnosing and monitoring various neurological conditions. EEG captures the brain's electrical activity, enabling clinicians to assess brain function, diagnose epilepsy, monitor anesthesia, and evaluate sleep disorders. SSEP measures the electrical responses of the nervous system to sensory stimuli, providing crucial information about the integrity of sensory pathways, aiding in the diagnosis of spinal cord injuries and peripheral nerve disorders, and assessing intraoperative neurophysiological integrity during surgeries.
Nevertheless, there is much space for improvement regarding the applications of these techniques to clinical practices, for example, to more precisely monitor anesthetic depth and to guide the use of hypothermia therapy and the prognosis of neurological recovery for cardiac arrest patients. Cardiac arrest often leads to significant neurological damage, and predicting the neurological outcome accurately is challenging yet essential for guiding clinical management and decision-making. By identifying specific electrophysiological signatures associated with favorable or unfavorable outcomes, clinicians can make timely and informed decisions regarding therapeutic interventions, prognostication, and potentially tailoring individualized treatment strategies.
This thesis develops a novel recording modality named the Extended Evoked Response Potential (EERP). Based on the well-validated and widely used EEG and SSEP techniques, EERP attempts to combine both and offer a more comprehensive perspective of the status and dynamics of neural activities. Chapter 1 provides a comprehensive literature review of the neurobiological foundations of arousal and the applications of electrophysiological tools for clinical purposes. Chapter 2 describes this thesis study's theoretical principles and experimental settings. Chapter 3 demonstrates the use of EERP in both anesthesia and cardiac arrest experiments, and the results are shown. Chapter 4 evaluates the ear as a potential location for the non-invasive recording of SSEP. Chapter 5 concludes the findings of the thesis work and discusses future investigations
Search For Electrophysiological Biomarkers Of Arousal In Anesthesia And After Cardiac Arrest
No full textElectrophysiological recordings, notably Electroencephalography (EEG) and Somatosensory Evoked Potentials (SSEP) play pivotal roles in clinical settings, offering insights into the functioning of the nervous system and aiding in diagnosing and monitoring various neurological conditions. EEG captures the brain's electrical activity, enabling clinicians to assess brain function, diagnose epilepsy, monitor anesthesia, and evaluate sleep disorders. SSEP measures the electrical responses of the nervous system to sensory stimuli, providing crucial information about the integrity of sensory pathways, aiding in the diagnosis of spinal cord injuries and peripheral nerve disorders, and assessing intraoperative neurophysiological integrity during surgeries.
Nevertheless, there is much space for improvement regarding the applications of these techniques to clinical practices, for example, to more precisely monitor anesthetic depth and to guide the use of hypothermia therapy and the prognosis of neurological recovery for cardiac arrest patients. Cardiac arrest often leads to significant neurological damage, and predicting the neurological outcome accurately is challenging yet essential for guiding clinical management and decision-making. By identifying specific electrophysiological signatures associated with favorable or unfavorable outcomes, clinicians can make timely and informed decisions regarding therapeutic interventions, prognostication, and potentially tailoring individualized treatment strategies.
This thesis develops a novel recording modality named the Extended Evoked Response Potential (EERP). Based on the well-validated and widely used EEG and SSEP techniques, EERP attempts to combine both and offer a more comprehensive perspective of the status and dynamics of neural activities. Chapter 1 provides a comprehensive literature review of the neurobiological foundations of arousal and the applications of electrophysiological tools for clinical purposes. Chapter 2 describes this thesis study's theoretical principles and experimental settings. Chapter 3 demonstrates the use of EERP in both anesthesia and cardiac arrest experiments, and the results are shown. Chapter 4 evaluates the ear as a potential location for the non-invasive recording of SSEP. Chapter 5 concludes the findings of the thesis work and discusses future investigations
Investigating the Effect of Selected Non-Saccharomyces Species on Wine Ecosystem Function and Major Volatiles
No full textNatural alcoholic fermentation is initiated by a diverse population of several non-Saccharomyces yeast species. However, most of the species progressively die off, leaving only a few strongly fermentative species, mainly Saccharomyces cerevisiae. The relative performance of each yeast species is dependent on its fermentation capacity, initial cell density, ecological interactions as well as tolerance to environmental factors. However, the fundamental rules underlying the working of the wine ecosystem are not fully understood. Here we use variation in cell density as a tool to evaluate the impact of individual non-Saccharomyces wine yeast species on fermentation kinetics and population dynamics of a multi-species yeast consortium in synthetic grape juice fermentation. Furthermore, the impact of individual species on aromatic properties of wine was investigated, using Gas Chromatography-Flame Ionization Detector. Fermentation kinetics was affected by the inoculation treatment. The results show that some non-Saccharomyces species support or inhibit the growth of other non-Saccharomyces species in the multi-species consortium. Overall, the fermentation inoculated with a high cell density of Starmerella bacillaris displayed the fastest fermentation kinetics while fermentation inoculated with Hanseniaspora vineae showed the slowest kinetics. The production of major volatiles was strongly affected by the treatments, and the aromatic signature could in some cases be linked to specific non-Saccharomyces species. In particular, Wickerhamomyces anomalus at high cell density contributed to elevated levels of 2-Phenylethan-1-ol whereas Starm. bacillaris at high cell density resulted in the high production of 2-methylpropanoic acid and 3-Hydroxybutanone. The data revealed possible direct and indirect influences of individual non-Saccharomyces species within a complex consortium, on wine chemical composition
INVESTIGATION OF OPERATING CONDITION OF DISTRICT HEATING AND COOLING (DHC) PLANTS IN CENTRAL TOKYO AREA
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Dynamics of Advice Network and Knowledge Contribution: A Longitudinal Social Network Analysis
No full textOnline communities have become an increasingly popular channel for social interaction, enabling knowledge and opinion sharing across a board range of topics and contexts. Their viability and sustainability depends largely on contributions from community members in terms of time, resources, and knowledge. However, how individuals' knowledge contribution behavior changes over time and what network structural characteristics influence individuals' contribution behavior is not well understood. This study investigates "co-evolution" of social networks (i.e. advice network) and knowledge contribution behavior thorough a lens of social selection and social influence mechanism. This study are particularly interested in examining the dynamics of the advice network ties and the knowledge contribution behavior in the context of virtual financial communities in which people voluntarily participate to exchanges investing-related information. Unlike popular friendship-based online social networks, virtual financial communities in this study enables members to construct their own advice network by adding, maintaining, or terminating advice ties. Changes in network ties are referred to as social selection, while changes in individuals' behavior in response to the current network position are referred to as social influence. Dynamic network modeling is applied to investigate effects of social selection and influence separately and then examine the interplay between social selection and behavioral influence. Examination of such effects both separately and simultaneously requires a longitudinal data that capture dynamic changes in both the advice ties and the behavior under study.Release after 09-Aug-2014Originally embargoed until 09-Aug-2014; further restricted on 22-Jan-2016 per author request / K
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