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Comparative functional genomics identifies an iron-limited bottleneck in a Saccharomyces cerevisiae strain with a cytosolic-localized isobutanol pathway

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Synthetic and Systems Biotechnology 2022年第2期7卷 738-749页

作者： Francesca V.Gambacorta Ellen R.Wagner Tyler B.Jacobson Mary Tremaine Laura K.Muehlbauer Mick A.McGee Justin J.Baerwald Russell L.Wrobel john F.wolters Mike Place Joshua J.Dietrich Dan Xie Jose Serate Shabda Gajbhiye Lisa Liu Maikayeng Vang-Smith Joshua J.Coon Yaoping Zhang Audrey P.Gasch Daniel Amador-Noguez Chris Todd Hittinger Trey K.Sato Brian F.Pfleger DOE Great Lakes Bioenergy Research Center University of Wisconsin-MadisonMadisonWIUSA Department of Chemical and Biological Engineering University of Wisconsin-MadisonMadisonWIUSA Laboratory of Genetics Center for Genomic Science InnovationUniversity of Wisconsin-MadisonMadisonWIUSA Department of Bacteriology University of Wisconsin-MadisonMadisonWIUSA Department of Chemistry University of Wisconsin-MadisonMadisonWIUSA Wisconsin Energy Institute J.F.Crow Institute for the Study of EvolutionUniversity of Wisconsin-MadisonMadisonWIUSA Department of Biomolecular Chemistry University of Wisconsin-MadisonMadisonWIUSA

Metabolic engineering strategies have been successfully implemented to improve the production of isobutanol,a next-generation biofuel,in Saccharomyces ***,we explore how two of these strategies,pathway re-localization and redox cofactor-balancing,affect the performance and physiology of isobutanol producing *** equipped yeast with isobutanol cassettes which had either a mitochondrial or cytosolic localized isobutanol pathway and used either a redox-imbalanced(NADPH-dependent)or redox-balanced(NADH-dependent)ketol-acid reductoisomerase *** then conducted transcriptomic,proteomic and metabolomic analyses to elucidate molecular differences between the engineered *** localization had a large effect on isobutanol production with the strain expressing the mitochondrial-localized enzymes producing 3.8-fold more isobutanol than strains expressing the cytosolic ***-balancing did not improve isobutanol titers and instead the strain with the redox-imbalanced pathway produced 1.5-fold more isobutanol than the balanced version,albeit at low overall pathway *** genomic analyses suggested that the poor performances of the cytosolic pathway strains were in part due to a shortage in cytosolic Fe-S clusters,which are required cofactors for the dihydroxyacid dehydratase *** then demonstrated that this cofactor limitation may be partially recovered by disrupting iron homeostasis with a fra2 mutation,thereby increasing cellular iron *** resulting isobutanol titer of the fra2 null strain harboring a cytosolic-localized isobutanol pathway outperformed the strain with the mitochondrial-localized pathway by 1.3-fold,demonstrating that both localizations can support flux to isobutanol.

关键词： Saccharomyces cerevisiae Isobutanol Functional genomics analysis Pathway localization Fe incorporation

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木质砌体外墙技术的新运用——卡马拉组学院的Arcus中心

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设计家 2015年第1期 92-95页

作者： Jeanne Gang Mark Schendel Todd Zima Margaret Cavenagh Claire Halpin with john Castro Juan de la Mora Ana Flor Ortiz (RA) Jay Hoffman Wei-Ju Lai Lindsey Moyer Jeana Ripple Schuyler Smith Rolf Temesvari john wolters Iwan Baan Steve Hall Hedrich Blessing GANG建筑事务所 Studio Gang Architects

从历史上看,寻求社会公义的集会,包括许多对这个国家来说最重要的人权集会常常发生在最非正式的场合,例如在某个教堂的地下室,在某个起居室,甚或只是围在厨房里的圆桌旁集会就形成了。想要设计一栋能够促进公开讨论并向所有人都开放的建... 详细信息

从历史上看,寻求社会公义的集会,包括许多对这个国家来说最重要的人权集会常常发生在最非正式的场合,例如在某个教堂的地下室,在某个起居室,甚或只是围在厨房里的圆桌旁集会就形成了。想要设计一栋能够促进公开讨论并向所有人都开放的建筑,从各个方面来说都是一个前所未有的挑战。设计Arcus中心的目的便是将社会公义的话题从地下室带入公共意识。

关键词：卡马拉公共意识 Arcus 公义弧形墙学校园社会公正人的生命内凹可达性

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Stepping up to meet the challenge of freezing of gait in Parkinson’s disease

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Translational Neurodegeneration 2022年第1期11卷 589-600页

作者： Simon Lewis Stewart Factor Nir Giladi Alice Nieuwboer john Nutt Mark Hallett ForeFront Parkinson’s Disease Research Clinic Brain and Mind CentreSchool of Medical SciencesUniversity of SydneySydneyNSWAustralia Jean and Paul Amos Parkinson’s Disease and Movement Disorders Program Emory University School of MedicineAtlantaGAUSA Movement Disorders Unit Department of NeurologyTel-Aviv Sourasky Medical CenterSackler School of Medicine and Sagol School of NeuroscienceTel Aviv UniversityTel AvivIsrael Department of Rehabilitation Sciences KU LeuvenLeuvenBelgium Movement Disorder Section Department of NeurologyOregon Health&Science UniversityPortlandORUSA Human Motor Control Section National Institute of Neurological Disorders and StrokeNational Institutes of HealthBethesdaMDUSA.

There has been a growing appreciation for freezing of gait as a disabling symptom that causes a significant burden in Parkinson’s disease. Previous research has highlighted some of the key components that underlie the phenomenon, but these reductionist approaches have yet to lead to a paradigm shift resulting in the development of novel treatment strategies. Addressing this issue will require greater integration of multi-modal data with complex computational modeling, but there are a number of critical aspects that need to be considered before embarking on such an approach. This paper highlights where the field needs to address current gaps and shortcomings including the standardization of definitions and measurement, phenomenology and pathophysiology, as well as considering what available data exist and how future studies should be constructed to achieve the greatest potential to better understand and treat this devastating symptom.

关键词： Freezing of gait Computational modeling Standardized definitions and assessments Novel paradigms Phenomenology Pathophysiology Treatment

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