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Article ; Online: Cell-Free Production of Protein Biologics Within 24 H.

Sullivan, Challise J / Pendleton, Erik D / Dresios, John

Methods in molecular biology (Clifton, N.J.)

2017 Volume 1674, Page(s) 95–107

Abstract: Protein biologics have emerged as a safe and effective group of drug products that can be used in a variety of medical disorders and clinical settings, including treatment of orphan diseases, personalized medicine, and point-of-care applications. However, ...

Abstract	Protein biologics have emerged as a safe and effective group of drug products that can be used in a variety of medical disorders and clinical settings, including treatment of orphan diseases, personalized medicine, and point-of-care applications. However, the full potential of protein biologics for such applications will not be realized until there are methods available for rapid and cost-effective production of small scale products for individual needs. Here, we describe a modular and scalable method for rapid and adaptable production of protein-based medical products at small doses. The method includes cell-free synthesis of the protein target in a reactor module followed by a fluidic process for protein purification. As a proof of concept, we describe the application of this method for expression and purification of a bioactive pharmaceutically relevant protein biologic, recombinant human erythropoietin, at a single dose within 24 h. This method can be applied toward the development of automated platforms for rapid and adaptive production of protein biologics at the point of care in response to specific medical needs.
MeSH term(s)	Biological Products/metabolism ; Cell-Free System/metabolism ; Cost-Benefit Analysis/methods ; Erythropoietin/metabolism ; Humans ; Recombinant Proteins/metabolism
Chemical Substances	Biological Products ; Recombinant Proteins ; Erythropoietin (11096-26-7)
Language	English
Publishing date	2017-09-14
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-4939-7312-5_8
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Article ; Online: Chromatin structure analysis enables detection of DNA insertions into the mammalian nuclear genome.

Sullivan, Challise J / Pendleton, Erik D / Abrams, Rachel E / Valente, David L / Alvarez, Michelle L / Griffey, Richard H / Dresios, John

Biochemistry and biophysics reports

2015 Volume 2, Page(s) 143–152

Abstract: Background: Genetically modified organisms (GMOs) have numerous biomedical, agricultural and environmental applications. Development of accurate methods for the detection of GMOs is a prerequisite for the identification and control of authorized and ... ...

Abstract	Background: Genetically modified organisms (GMOs) have numerous biomedical, agricultural and environmental applications. Development of accurate methods for the detection of GMOs is a prerequisite for the identification and control of authorized and unauthorized release of these engineered organisms into the environment and into the food chain. Current detection methods are unable to detect uncharacterized GMOs, since either the DNA sequence of the transgene or the amino acid sequence of the protein must be known for DNA-based or immunological-based detection, respectively. Methods: Here we describe the application of an epigenetics-based approach for the detection of mammalian GMOs Results: Immunological methods combined with DNA next generation sequencing enabled direct interrogation of chromatin structure and identification of insertions of various size foreign (human or viral) DNA sequences, DNA sequences often used as genome modification tools ( Conclusions: The results provide a proof-of-concept that epigenetic approaches can be used to detect the insertion of endogenous and exogenous sequences into the genome of higher organisms where the method of genetic modification, the sequence of inserted DNA, and the exact genomic insertion site(s) are unknown. General significance: Measurement of chromatin dynamics as a sensor for detection of genomic manipulation and, more broadly, organism exposure to environmental or other factors affecting the epigenomic landscape are discussed.
Language	English
Publishing date	2015-06-10
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2831046-9
ISSN	2405-5808 ; 2405-5808
ISSN (online)	2405-5808
ISSN	2405-5808
DOI	10.1016/j.bbrep.2015.06.002
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Article: Actin exposure upon tissue injury is a targetable wound site-specific protein marker.

Pendleton, Erik D / Sullivan, Challise J / Sasmor, Henri H / Bruse, Kristy D / Mayfield, Tifanie B / Valente, David L / Abrams, Rachel E / Griffey, Richard H / Dresios, John

Biochemistry and biophysics reports

2016 Volume 7, Page(s) 56–62

Abstract: Background: Identification of wound-specific markers would represent an important step toward damaged tissue detection and targeted delivery of biologically important materials to injured sites. Such delivery could minimize the amount of therapeutic ... ...

Abstract	Background: Identification of wound-specific markers would represent an important step toward damaged tissue detection and targeted delivery of biologically important materials to injured sites. Such delivery could minimize the amount of therapeutic materials that must be administered and limit potential collateral damage on nearby normal tissues. Yet, biological markers that are specific for injured tissue sites remain elusive. Methods: In this study, we have developed an immunohistological approach for identification of protein epitopes specifically exposed in wounded tissue sites. Results: Using Conclusions: These results illustrate that identification of injury-specific protein markers and their targetability for specific delivery is feasible. General significance: Identification of wound-specific targets has important medical applications as it could enable specific delivery of various products, such as expression vectors, therapeutic drugs, hemostatic materials, tissue healing, or scar prevention agents, to internal sites of penetrating or surgical wounds regardless of origin, geometry or location.
Language	English
Publishing date	2016-05-18
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2831046-9
ISSN	2405-5808
ISSN	2405-5808
DOI	10.1016/j.bbrep.2016.05.013
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Article: The relationship between financial participation and other forms of employee participation

Poutsma, Erik / Kalmi, Panu / Pendleton, Andrew D

Economic and industrial democracy : EID ; an international journal Vol. 27, No. 4 , p. 637-667

new survey evidence from Europe

2006 Volume 27, Issue 4, Page(s) 637–667

Author's details	Erik Poutsma; Panu Kalmi; Andrew D. Pendleton
Keywords	Mitarbeiterkapitalbeteiligung ; Europa ; 49
Language	English
Size	graph. Darst.
Publisher	Sage
Publishing place	London; Beverly Hills, Calif.
Document type	Article
ZDB-ID	762162-0
Database	ECONomics Information System

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Article ; Online: The EMIF-AD PreclinAD study: study design and baseline cohort overview.

Konijnenberg, Elles / Carter, Stephen F / Ten Kate, Mara / den Braber, Anouk / Tomassen, Jori / Amadi, Chinenye / Wesselman, Linda / Nguyen, Hoang-Ton / van de Kreeke, Jacoba A / Yaqub, Maqsood / Demuru, Matteo / Mulder, Sandra D / Hillebrand, Arjan / Bouwman, Femke H / Teunissen, Charlotte E / Serné, Erik H / Moll, Annette C / Verbraak, Frank D / Hinz, Rainer /

Pendleton, Neil / Lammertsma, Adriaan A / van Berckel, Bart N M / Barkhof, Frederik / Boomsma, Dorret I / Scheltens, Philip / Herholz, Karl / Visser, Pieter Jelle

Alzheimer's research & therapy

2018 Volume 10, Issue 1, Page(s) 75

Abstract: Background: Amyloid pathology is the pathological hallmark in Alzheimer's disease (AD) and can precede clinical dementia by decades. So far it remains unclear how amyloid pathology leads to cognitive impairment and dementia. To design AD prevention ... ...

Abstract	Background: Amyloid pathology is the pathological hallmark in Alzheimer's disease (AD) and can precede clinical dementia by decades. So far it remains unclear how amyloid pathology leads to cognitive impairment and dementia. To design AD prevention trials it is key to include cognitively normal subjects at high risk for amyloid pathology and to find predictors of cognitive decline in these subjects. These goals can be accomplished by targeting twins, with additional benefits to identify genetic and environmental pathways for amyloid pathology, other AD biomarkers, and cognitive decline. Methods: From December 2014 to October 2017 we enrolled cognitively normal participants aged 60 years and older from the ongoing Manchester and Newcastle Age and Cognitive Performance Research Cohort and the Netherlands Twins Register. In Manchester we included single individuals, and in Amsterdam monozygotic twin pairs. At baseline, participants completed neuropsychological tests and questionnaires, and underwent physical examination, blood sampling, ultrasound of the carotid arteries, structural and resting state functional brain magnetic resonance imaging, and dynamic amyloid positron emission tomography (PET) scanning with [ Results: We included 285 participants, who were on average 74.8 ± 9.7 years old, 64% female. Fifty-eight participants (22%) had an abnormal amyloid PET scan. Conclusions: A rich baseline dataset of cognitively normal elderly individuals has been established to estimate risk factors and biomarkers for amyloid pathology and future cognitive decline.
MeSH term(s)	Age Factors ; Aged ; Aged, 80 and over ; Alzheimer Disease/cerebrospinal fluid ; Alzheimer Disease/complications ; Alzheimer Disease/diagnostic imaging ; Alzheimer Disease/genetics ; Amyloid beta-Peptides/metabolism ; Aniline Compounds/pharmacokinetics ; Apolipoproteins E/genetics ; Benzothiazoles/pharmacokinetics ; Carotid Arteries/diagnostic imaging ; Cognition Disorders/etiology ; Cohort Studies ; Female ; Humans ; Imaging, Three-Dimensional ; International Cooperation ; Magnetic Resonance Imaging ; Magnetoencephalography ; Male ; Middle Aged ; Neuropsychological Tests ; Positron-Emission Tomography ; Tomography, Optical Coherence
Chemical Substances	Amyloid beta-Peptides ; Aniline Compounds ; Apolipoproteins E ; Benzothiazoles ; flutemetamol (0F3M7032P5)
Language	English
Publishing date	2018-08-04
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Twin Study
ZDB-ID	2506521-X
ISSN	1758-9193 ; 1758-9193
ISSN (online)	1758-9193
ISSN	1758-9193
DOI	10.1186/s13195-018-0406-7
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Article ; Online: A cell-free expression and purification process for rapid production of protein biologics.

Sullivan, Challise J / Pendleton, Erik D / Sasmor, Henri H / Hicks, William L / Farnum, John B / Muto, Machiko / Amendt, Eric M / Schoborg, Jennifer A / Martin, Rey W / Clark, Lauren G / Anderson, Mark J / Choudhury, Alaksh / Fior, Raffaella / Lo, Yu-Hwa / Griffey, Richard H / Chappell, Stephen A / Jewett, Michael C / Mauro, Vincent P / Dresios, John

Biotechnology journal

2016 Volume 11, Issue 2, Page(s) 238–248

Abstract: Cell-free protein synthesis has emerged as a powerful technology for rapid and efficient protein production. Cell-free methods are also amenable to automation and such systems have been extensively used for high-throughput protein production and ... ...

Abstract	Cell-free protein synthesis has emerged as a powerful technology for rapid and efficient protein production. Cell-free methods are also amenable to automation and such systems have been extensively used for high-throughput protein production and screening; however, current fluidic systems are not adequate for manufacturing protein biopharmaceuticals. In this work, we report on the initial development of a fluidic process for rapid end-to-end production of recombinant protein biologics. This process incorporates a bioreactor module that can be used with eukaryotic or prokaryotic lysates that are programmed for combined transcription/translation of an engineered DNA template encoding for specific protein targets. Purification of the cell-free expressed product occurs through a series of protein separation modules that are configurable for process-specific isolation of different proteins. Using this approach, we demonstrate production of two bioactive human protein therapeutics, erythropoietin and granulocyte-macrophage colony-stimulating factor, in yeast and bacterial extracts, respectively, each within 24 hours. This process is flexible, scalable and amenable to automation for rapid production at the point-of-need of proteins with significant pharmaceutical, medical, or biotechnological value.
MeSH term(s)	Biological Products/isolation & purification ; Biological Products/metabolism ; Bioreactors ; Cell-Free System ; Erythropoietin/biosynthesis ; Erythropoietin/genetics ; Erythropoietin/isolation & purification ; Granulocyte-Macrophage Colony-Stimulating Factor/biosynthesis ; Granulocyte-Macrophage Colony-Stimulating Factor/genetics ; Granulocyte-Macrophage Colony-Stimulating Factor/isolation & purification ; Humans ; Metabolic Engineering/methods ; Recombinant Proteins/biosynthesis ; Recombinant Proteins/genetics ; Recombinant Proteins/isolation & purification ; Technology, Pharmaceutical/methods
Chemical Substances	Biological Products ; Recombinant Proteins ; Erythropoietin (11096-26-7) ; Granulocyte-Macrophage Colony-Stimulating Factor (83869-56-1)
Language	English
Publishing date	2016-02
Publishing country	Germany
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2221885-3
ISSN	1860-7314 ; 1860-6768
ISSN (online)	1860-7314
ISSN	1860-6768
DOI	10.1002/biot.201500214
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Article: Environmental predictors of stream flow in semi-arid watersheds for biological assessments

Giraldo, Mario A / Dark, Shawna / Pendleton, Patricia / Stein, Eric D / Mazor, Raphael / Andreas, Josh

Ecological indicators. 2019 May 08,

2019

Abstract: The aim of this study is to test a spatially explicit statistical model to identify indicators of natural stream flow using readily available stream, climate and landscape data. Understanding flow behavior of unmonitored streams at different temporal ... ...

Abstract	The aim of this study is to test a spatially explicit statistical model to identify indicators of natural stream flow using readily available stream, climate and landscape data. Understanding flow behavior of unmonitored streams at different temporal scales using environmental indicators is of great interest considering the logistic constraints of providing comprehensive flow instrumentation for all stream reaches in a region. Our results have applications to assess human impact in watersheds, to study environmental changes in fresh water resources, and in the management of local ecosystem. This study uses classification and regression tree analysis to identify significant explanatory variables for a predictive model of stream flow in semi-arid watersheds of southern California, USA. The study collected 77 variables with 30 years record, for a set of 48 sites, interpolated to create raster files at 30m spatial resolution. After applying Pearson correlation analyses to eliminate redundant variables, nine variables were found to have strong positive predictive value for estimating stream flow at ungauged sites. Nine prediction rasters portraying spatial variation of stream flow for the study region at three key index months during wet, dry, and average rainfall conditions. The predictive power of the variables was tested and cross validated over a subset of data not included when building the model. Model validation by site at monthly temporal resolution showed mixed results. While some sites where accurately predicted others did not. The comparison of observed vs predicted values by month suggest that this statistically based approach is able to predict the general patterns of stream flow at the regional scale, however it may be inaccurate in estimating actual flow values by month since the models tends to under-predict monthly discharge.
Keywords	anthropogenic activities ; climate ; ecosystems ; environmental indicators ; freshwater ; instrumentation ; landscapes ; model validation ; prediction ; rain ; regression analysis ; statistical models ; stream flow ; streams ; watersheds ; California
Language	English
Dates of publication	2019-0508
Publishing place	Elsevier Ltd
Document type	Article
Note	Pre-press version
ZDB-ID	2036774-0
ISSN	1872-7034 ; 1470-160X
ISSN (online)	1872-7034
ISSN	1470-160X
DOI	10.1016/j.ecolind.2019.05.019
Database	NAL-Catalogue (AGRICOLA)

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Article: The impact of climate change on California’s ecosystem services

Shaw, M. Rebecca / Pendleton, Linwood / Cameron, D. Richard / Morris, Belinda / Bachelet, Dominique / Klausmeyer, Kirk / MacKenzie, Jason / Conklin, David R / Bratman, Gregrory N / Lenihan, James / Haunreiter, Erik / Daly, Christopher / Roehrdanz, Patrick R

Climatic change. 2011 Dec., v. 109, no. Supplement 1

2011

Abstract: Ecosystem services play a crucial role in sustaining human well-being and economic viability. People benefit substantially from the delivery of ecosystem services, for which substitutes usually are costly or unavailable. Climate change will substantially ...

Abstract	Ecosystem services play a crucial role in sustaining human well-being and economic viability. People benefit substantially from the delivery of ecosystem services, for which substitutes usually are costly or unavailable. Climate change will substantially alter or eliminate certain ecosystem services in the future. To better understand the consequences of climate change and to develop effective means of adapting to them, it is critical that we improve our understanding of the links between climate, ecosystem service production, and the economy. This study examines the impact of climate change on the terrestrial distribution and the subsequent production and value of two key ecosystem services in California: (1) carbon sequestration and (2) natural (i.e. non-irrigated) forage production for livestock. Under various scenarios of future climate change, we predict that the provision and value of ecosystem services decline under most, but not all, future greenhouse gas trajectories. The predicted changes would result in decreases in the economic output for the state and global economy and illustrate some of the hidden costs of climate change. Since existing information is insufficient to conduct impact analysis across most ecosystem services, a comprehensive research program focused on estimating the impacts of climate change on ecosystem services will be important for understanding, mitigating and adapting to future losses in ecosystem service production and the economic value they provide.
Keywords	carbon sequestration ; climate ; climate change ; economic valuation ; ecosystem services ; forage production ; greenhouse gases ; humans ; livestock production ; people ; prediction ; research programs ; viability ; California
Language	English
Dates of publication	2011-12
Size	p. 465-484.
Publishing place	Springer-Verlag
Document type	Article
ZDB-ID	751086-x
ISSN	0165-0009
ISSN	0165-0009
DOI	10.1007/s10584-011-0313-4
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Article ; Online: An integrated map of structural variation in 2,504 human genomes.

Sudmant, Peter H / Rausch, Tobias / Gardner, Eugene J / Handsaker, Robert E / Abyzov, Alexej / Huddleston, John / Zhang, Yan / Ye, Kai / Jun, Goo / Fritz, Markus Hsi-Yang / Konkel, Miriam K / Malhotra, Ankit / Stütz, Adrian M / Shi, Xinghua / Casale, Francesco Paolo / Chen, Jieming / Hormozdiari, Fereydoun / Dayama, Gargi / Chen, Ken /

Malig, Maika / Chaisson, Mark J P / Walter, Klaudia / Meiers, Sascha / Kashin, Seva / Garrison, Erik / Auton, Adam / Lam, Hugo Y K / Mu, Xinmeng Jasmine / Alkan, Can / Antaki, Danny / Bae, Taejeong / Cerveira, Eliza / Chines, Peter / Chong, Zechen / Clarke, Laura / Dal, Elif / Ding, Li / Emery, Sarah / Fan, Xian / Gujral, Madhusudan / Kahveci, Fatma / Kidd, Jeffrey M / Kong, Yu / Lameijer, Eric-Wubbo / McCarthy, Shane / Flicek, Paul / Gibbs, Richard A / Marth, Gabor / Mason, Christopher E / Menelaou, Androniki / Muzny, Donna M / Nelson, Bradley J / Noor, Amina / Parrish, Nicholas F / Pendleton, Matthew / Quitadamo, Andrew / Raeder, Benjamin / Schadt, Eric E / Romanovitch, Mallory / Schlattl, Andreas / Sebra, Robert / Shabalin, Andrey A / Untergasser, Andreas / Walker, Jerilyn A / Wang, Min / Yu, Fuli / Zhang, Chengsheng / Zhang, Jing / Zheng-Bradley, Xiangqun / Zhou, Wanding / Zichner, Thomas / Sebat, Jonathan / Batzer, Mark A / McCarroll, Steven A / Mills, Ryan E / Gerstein, Mark B / Bashir, Ali / Stegle, Oliver / Devine, Scott E / Lee, Charles / Eichler, Evan E / Korbel, Jan O

Nature

2015 Volume 526, Issue 7571, Page(s) 75–81

Abstract: Structural variants are implicated in numerous diseases and make up the majority of varying nucleotides among human genomes. Here we describe an integrated set of eight structural variant classes comprising both balanced and unbalanced variants, which we ...

Abstract	Structural variants are implicated in numerous diseases and make up the majority of varying nucleotides among human genomes. Here we describe an integrated set of eight structural variant classes comprising both balanced and unbalanced variants, which we constructed using short-read DNA sequencing data and statistically phased onto haplotype blocks in 26 human populations. Analysing this set, we identify numerous gene-intersecting structural variants exhibiting population stratification and describe naturally occurring homozygous gene knockouts that suggest the dispensability of a variety of human genes. We demonstrate that structural variants are enriched on haplotypes identified by genome-wide association studies and exhibit enrichment for expression quantitative trait loci. Additionally, we uncover appreciable levels of structural variant complexity at different scales, including genic loci subject to clusters of repeated rearrangement and complex structural variants with multiple breakpoints likely to have formed through individual mutational events. Our catalogue will enhance future studies into structural variant demography, functional impact and disease association.
MeSH term(s)	Amino Acid Sequence ; Genetic Predisposition to Disease ; Genetic Variation/genetics ; Genetics, Medical ; Genetics, Population ; Genome, Human/genetics ; Genome-Wide Association Study ; Genomics ; Genotype ; Haplotypes/genetics ; Homozygote ; Humans ; Molecular Sequence Data ; Mutation Rate ; Physical Chromosome Mapping ; Polymorphism, Single Nucleotide/genetics ; Quantitative Trait Loci/genetics ; Sequence Analysis, DNA ; Sequence Deletion/genetics
Language	English
Publishing date	2015-10-02
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	120714-3
ISSN	1476-4687 ; 0028-0836
ISSN (online)	1476-4687
ISSN	0028-0836
DOI	10.1038/nature15394
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