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Elizabeth H. Williams

Bio: Elizabeth H. Williams is an academic researcher from Johns Hopkins University. The author has contributed to research in topics: Social media & Mobile device. The author has an hindex of 17, co-authored 36 publications receiving 2166 citations. Previous affiliations of Elizabeth H. Williams include University College London & Rockefeller University.

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Journal ArticleDOI
TL;DR: It is shown that the soz1 mutant is hypersensitive to both sulfur dioxide and ultraviolet B irradiation, thus implicating ascorbate in defense against varied environmental stresses and indicating that screening for ozone-sensitive mutants is a powerful method for identifying physiologically important antioxidant mechanisms and signal transduction pathways.
Abstract: L-ascorbic acid (vitamin C) is a powerful reducing agent found in millimolar concentrations in plants, and is proposed to play an important role in scavenging free radicals in plants and animals. However, surprisingly little is known about the role of this antioxidant in plant environmental stress adaptation or ascorbate biosynthesis. We report the isolation of soz1, a semi-dominant ozone-sensitive mutant that accumulates only 30% of the normal ascorbate concentration. The results of genetic approaches and feeding studies show that the ascorbate concentration affects foliar resistance to the oxidizing gas ozone. Consistent with the proposed role for ascorbate in reactive oxygen species detoxification, lipid peroxides are elevated in soz1, but not in wild type following ozone fumigation. We show that the soz1 mutant is hypersensitive to both sulfur dioxide and ultraviolet B irradiation, thus implicating ascorbate in defense against varied environmental stresses. In addition to defining the first ascorbate deficient mutant in plants, these results indicate that screening for ozone-sensitive mutants is a powerful method for identifying physiologically important antioxidant mechanisms and signal transduction pathways. Analysis of soz1 should lead to more information about the physiological roles and metabolism of ascorbate.

525 citations

Journal ArticleDOI
TL;DR: By using a combination of biochemical, molecular, and genetic techniques, it is demonstrated that the VTC1 locus encodes a GDP-mannose pyrophosphorylase (mannose-1-P guanyltransferase).
Abstract: Vitamin C (L-ascorbic acid; AsA) acts as a potent antioxidant and cellular reductant in plants and animals AsA has long been known to have many critical physiological roles in plants, yet its biosynthesis is only currently being defined A pathway for AsA biosynthesis that features GDP-mannose and L-galactose has recently been proposed for plants We have isolated a collection of AsA-deficient mutants of Arabidopsis thaliana that are valuable tools for testing of an AsA biosynthetic pathway The best-characterized of these mutants (vtc1) contains approximately 25% of wild-type AsA and is defective in AsA biosynthesis By using a combination of biochemical, molecular, and genetic techniques, we have demonstrated that the VTC1 locus encodes a GDP-mannose pyrophosphorylase (mannose-1-P guanyltransferase) This enzyme provides GDP-mannose, which is used for cell wall carbohydrate biosynthesis and protein glycosylation as well as for AsA biosynthesis In addition to genetically defining the first locus involved in AsA biosynthesis, this work highlights the power of using traditional mutagenesis techniques coupled with the Arabidopsis Genome Initiative to rapidly clone physiologically important genes

385 citations

Journal ArticleDOI
Alexandra B Keenan1, Sherry L. Jenkins1, Kathleen M. Jagodnik1, Simon Koplev1, Edward He1, Denis Torre1, Zichen Wang1, Anders B. Dohlman1, Moshe C. Silverstein1, Alexander Lachmann1, Maxim V. Kuleshov1, Avi Ma'ayan1, Vasileios Stathias2, Raymond Terryn2, Daniel J. Cooper2, Michele Forlin2, Amar Koleti2, Dusica Vidovic2, Caty Chung2, Stephan C. Schürer2, Jouzas Vasiliauskas3, Marcin Pilarczyk3, Behrouz Shamsaei3, Mehdi Fazel3, Yan Ren3, Wen Niu3, Nicholas A. Clark3, Shana White3, Naim Al Mahi3, Lixia Zhang3, Michal Kouril3, John F. Reichard3, Siva Sivaganesan3, Mario Medvedovic3, Jaroslaw Meller3, Rick J. Koch1, Marc R. Birtwistle1, Ravi Iyengar1, Eric A. Sobie1, Evren U. Azeloglu1, Julia A. Kaye4, Jeannette Osterloh4, Kelly Haston4, Jaslin Kalra4, Steve Finkbiener4, Jonathan Z. Li5, Pamela Milani5, Miriam Adam5, Renan Escalante-Chong5, Karen Sachs5, Alexander LeNail5, Divya Ramamoorthy5, Ernest Fraenkel5, Gavin Daigle6, Uzma Hussain6, Alyssa Coye6, Jeffrey D. Rothstein6, Dhruv Sareen7, Loren Ornelas7, Maria G. Banuelos7, Berhan Mandefro7, Ritchie Ho7, Clive N. Svendsen7, Ryan G. Lim8, Jennifer Stocksdale8, Malcolm Casale8, Terri G. Thompson8, Jie Wu8, Leslie M. Thompson8, Victoria Dardov7, Vidya Venkatraman7, Andrea Matlock7, Jennifer E. Van Eyk7, Jacob D. Jaffe9, Malvina Papanastasiou9, Aravind Subramanian9, Todd R. Golub, Sean D. Erickson10, Mohammad Fallahi-Sichani10, Marc Hafner10, Nathanael S. Gray10, Jia-Ren Lin10, Caitlin E. Mills10, Jeremy L. Muhlich10, Mario Niepel10, Caroline E. Shamu10, Elizabeth H. Williams10, David Wrobel10, Peter K. Sorger10, Laura M. Heiser11, Joe W. Gray11, James E. Korkola11, Gordon B. Mills12, Mark A. LaBarge13, Mark A. LaBarge14, Heidi S. Feiler11, Mark A. Dane11, Elmar Bucher11, Michel Nederlof11, Damir Sudar11, Sean M. Gross11, David Kilburn11, Rebecca Smith11, Kaylyn Devlin11, Ron Margolis, Leslie Derr, Albert Lee, Ajay Pillai 
TL;DR: The LINCS program focuses on cellular physiology shared among tissues and cell types relevant to an array of diseases, including cancer, heart disease, and neurodegenerative disorders.
Abstract: The Library of Integrated Network-Based Cellular Signatures (LINCS) is an NIH Common Fund program that catalogs how human cells globally respond to chemical, genetic, and disease perturbations. Resources generated by LINCS include experimental and computational methods, visualization tools, molecular and imaging data, and signatures. By assembling an integrated picture of the range of responses of human cells exposed to many perturbations, the LINCS program aims to better understand human disease and to advance the development of new therapies. Perturbations under study include drugs, genetic perturbations, tissue micro-environments, antibodies, and disease-causing mutations. Responses to perturbations are measured by transcript profiling, mass spectrometry, cell imaging, and biochemical methods, among other assays. The LINCS program focuses on cellular physiology shared among tissues and cell types relevant to an array of diseases, including cancer, heart disease, and neurodegenerative disorders. This Perspective describes LINCS technologies, datasets, tools, and approaches to data accessibility and reusability.

300 citations

Journal ArticleDOI
Orit Rozenblatt-Rosen1, Aviv Regev2, Aviv Regev1, Aviv Regev3  +370 moreInstitutions (19)
16 Apr 2020-Cell
TL;DR: The Human Tumor Atlas Network (HTAN), part of the NCI Cancer Moonshot Initiative, will establish a clinical, experimental, computational, and organizational framework to generate informative and accessible three-dimensional atlases of cancer transitions for a diverse set of tumor types.

279 citations

Journal ArticleDOI
TL;DR: Stillbirths and deaths on the day of birth represent a large proportion of perinatal and neonatal deaths, highlighting an urgent need to improve coverage with skilled birth attendants and to ensure access to emergency obstetric care.
Abstract: OBJECTIVE: To assess the rates, timing and causes of neonatal deaths and the burden of stillbirths in rural Uttar Pradesh, India. We discuss the implications of our findings for neonatal interventions. METHODS: We used verbal autopsy interviews to investigate 1048 neonatal deaths and stillbirths. FINDINGS: There were 430 stillbirths reported, comprising 41% of all deaths in the sample. Of the 618 live births, 32% deaths were on the day of birth, 50% occurred during the first 3 days of life and 71% were during the first week. The primary causes of death on the first day of life (i.e. day 0) were birth asphyxia or injury (31%) and preterm birth (26%). During days 1-6, the most frequent causes of death were preterm birth (30%) and sepsis or pneumonia (25%). Half of all deaths caused by sepsis or pneumonia occurred during the first week of life. The proportion of deaths attributed to sepsis or pneumonia increased to 45% and 36% during days 7-13 and 14-27, respectively. CONCLUSION: Stillbirths and deaths on the day of birth represent a large proportion of perinatal and neonatal deaths, highlighting an urgent need to improve coverage with skilled birth attendants and to ensure access to emergency obstetric care. Health interventions to improve essential neonatal care and care-seeking behavior are also needed, particularly for preterm neonates in the early postnatal period.

211 citations


Cited by
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TL;DR: The mechanisms of ROS generation and removal in plants during development and under biotic and abiotic stress conditions are described and the possible functions and mechanisms for ROS sensing and signaling in plants are compared with those in animals and yeast.
Abstract: Several reactive oxygen species (ROS) are continuously produced in plants as byproducts of aerobic metabolism. Depending on the nature of the ROS species, some are highly toxic and rapidly detoxified by various cellular enzymatic and nonenzymatic mechanisms. Whereas plants are surfeited with mechanisms to combat increased ROS levels during abiotic stress conditions, in other circumstances plants appear to purposefully generate ROS as signaling molecules to control various processes including pathogen defense, programmed cell death, and stomatal behavior. This review describes the mechanisms of ROS generation and removal in plants during development and under biotic and abiotic stress conditions. New insights into the complexity and roles that ROS play in plants have come from genetic analyses of ROS detoxifying and signaling mutants. Considering recent ROS-induced genome-wide expression analyses, the possible functions and mechanisms for ROS sensing and signaling in plants are compared with those in animals and yeast.

9,908 citations

Journal ArticleDOI
TL;DR: Key steps of the signal transduction pathway that senses ROIs in plants have been identified and raise several intriguing questions about the relationships between ROI signaling, ROI stress and the production and scavenging ofROIs in the different cellular compartments.

9,395 citations

Journal ArticleDOI
01 Jun 1998
TL;DR: A detailed account of current knowledge of the biosynthesis, compartmentation, and transport of these two important antioxidants, with emphasis on the unique insights and advances gained by molecular exploration are provided.
Abstract: To cope with environmental fluctuations and to prevent invasion by pathogens, plant metabolism must be flexible and dynamic. Active oxygen species, whose formation is accelerated under stress conditions, must be rapidly processed if oxidative damage is to be averted. The lifetime of active oxygen species within the cellular environment is determined by the antioxidative system, which provides crucial protection against oxidative damage. The antioxidative system comprises numerous enzymes and compounds of low molecular weight. While research into the former has benefited greatly from advances in molecular technology, the pathways by which the latter are synthesized have received comparatively little attention. The present review emphasizes the roles of ascorbate and glutathione in plant metabolism and stress tolerance. We provide a detailed account of current knowledge of the biosynthesis, compartmentation, and transport of these two important antioxidants, with emphasis on the unique insights and advances gained by molecular exploration.

5,450 citations

Journal ArticleDOI
01 Jun 2000
TL;DR: Evidence for plant stress signaling systems is summarized, some of which have components analogous to those that regulate osmotic stress responses of yeast, some that presumably function in intercellular coordination or regulation of effector genes in a cell-/tissue-specific context required for tolerance of plants.
Abstract: ▪ Abstract Plant responses to salinity stress are reviewed with emphasis on molecular mechanisms of signal transduction and on the physiological consequences of altered gene expression that affect biochemical reactions downstream of stress sensing. We make extensive use of comparisons with model organisms, halophytic plants, and yeast, which provide a paradigm for many responses to salinity exhibited by stress-sensitive plants. Among biochemical responses, we emphasize osmolyte biosynthesis and function, water flux control, and membrane transport of ions for maintenance and re-establishment of homeostasis. The advances in understanding the effectiveness of stress responses, and distinctions between pathology and adaptive advantage, are increasingly based on transgenic plant and mutant analyses, in particular the analysis of Arabidopsis mutants defective in elements of stress signal transduction pathways. We summarize evidence for plant stress signaling systems, some of which have components analogous to t...

4,596 citations

Journal ArticleDOI
TL;DR: Factors which possibly affect the effectiveness of antioxidant protection under oxygen deprivation as well as under other environmental stresses are presented.

3,562 citations