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George Church

Jonathan T Macy, Elizabeth A S Moser, Adam T Hirsh, Patrick O Monahan, George J Eckert, Gerardo Maupomé
BACKGROUND: Mexican immigrants in the United States suffer from poor oral health. The objective of the current study was to explore the utility of applying theory-based factors associated with seeking preventive dental care in a sample of Mexican American adults. METHODS: Data were collected from a cross-sectional survey of a sample of 157 people of Mexican origin (64% female; age 34 ± 11 years) recruited primarily from church congregations and lay community organizations in Central Indiana...
March 12, 2018: BMC Oral Health
Joseph T Church, Elena M Perkins, Megan A Coughlin, Jennifer S McLeod, Katherine Boss, J Kelley Bentley, Marc B Hershenson, Raja Rabah, Robert H Bartlett, George B Mychaliska
BACKGROUND: Extremely premature neonates suffer high morbidity and mortality. An artificial placenta (AP) using extracorporeal life support (ECLS) is a promising therapy. OBJECTIVES: We hypothesized that intratracheal perfluorocarbon (PFC) instillation during AP support would reduce lung injury and promote lung development relative to intratracheal amniotic fluid or crystalloid. METHODS: Lambs at an estimated gestational age (EGA) 116-121 days (term 145 days) were placed on venovenous ECLS with jugular drainage and umbilical vein reinfusion and intubated...
February 23, 2018: Neonatology
Timothy M Wannier, Aditya M Kunjapur, Daniel P Rice, Michael J McDonald, Michael M Desai, George M Church
Efforts are underway to construct several recoded genomes anticipated to exhibit multivirus resistance, enhanced nonstandard amino acid (nsAA) incorporation, and capability for synthetic biocontainment. Although our laboratory pioneered the first genomically recoded organism ( Escherichia coli strain C321.∆A), its fitness is far lower than that of its nonrecoded ancestor, particularly in defined media. This fitness deficit severely limits its utility for nsAA-linked applications requiring defined media, such as live cell imaging, metabolic engineering, and industrial-scale protein production...
February 13, 2018: Proceedings of the National Academy of Sciences of the United States of America
Michael J McGeachie, George L Clemmer, Boris Hayete, Heming Xing, Karl Runge, Ann Chen Wu, Xiaofeng Jiang, Quan Lu, Bruce Church, Iya Khalil, Kelan Tantisira, Scott Weiss
BACKGROUND: Variation in response to the most commonly used class of asthma controller medication, inhaled corticosteroids (ICS), presents a serious challenge in asthma management, particularly for steroid-resistant patients who display little or no response to treatment. OBJECTIVE: We applied a systems-biology approach to primary clinical and genomic data to identify and validate genes that modulate steroid response in children with asthma. METHODS: We selected 104 ICS-treated asthmatic non-Hispanic white children and determined a Steroid Responsiveness Endophenotype (SRE) using observations of six clinical measures over four years...
January 30, 2018: Journal of Allergy and Clinical Immunology
Jeff Nivala, Seth L Shipman, George M Church
The adaptation phase of CRISPR-Cas immunity depends on the precise integration of short segments of foreign DNA (spacers) into a specific genomic location within the CRISPR locus by the Cas1-Cas2 integration complex. Although off-target spacer integration outside of canonical CRISPR arrays has been described in vitro, no evidence of non-specific integration activity has been found in vivo. Here, we show that non-canonical off-target integrations can occur within bacterial chromosomes at locations that resemble the native CRISPR locus by characterizing hundreds of off-target integration locations within Escherichia coli...
January 29, 2018: Nature Microbiology
Richie E Kohman, Aditya M Kunjapur, Eriona Hysolli, Yu Wang, George M Church
Since the elucidation of its structure, DNA has been at the forefront of biological research. In the past half century, an explosion of DNA-based technology development has occurred with the most rapid advances being made for DNA sequencing. In parallel, dramatic improvements have also been made in the synthesis and editing of DNA from the oligonucleotide to the genome scale. In this Review, we will summarize four different subfields relating to DNA technologies following this trajectory of smaller to larger scale...
January 9, 2018: Angewandte Chemie
Aditya M Kunjapur, Devon A Stork, Erkin Kuru, Oscar Vargas-Rodriguez, Matthieu Landon, Dieter Söll, George M Church
Incorporation of nonstandard amino acids (nsAAs) leads to chemical diversification of proteins, which is an important tool for the investigation and engineering of biological processes. However, the aminoacyl-tRNA synthetases crucial for this process are polyspecific in regard to nsAAs and standard amino acids. Here, we develop a quality control system called "posttranslational proofreading" to more accurately and rapidly evaluate nsAA incorporation. We achieve this proofreading by hijacking a natural pathway of protein degradation known as the N-end rule, which regulates the lifespan of a protein based on its amino-terminal residue...
January 4, 2018: Proceedings of the National Academy of Sciences of the United States of America
David B Thompson, Soufiane Aboulhouda, Eriona Hysolli, Cory J Smith, Stan Wang, Oscar Castanon, George M Church
Multiplex genome editing is the simultaneous introduction of multiple distinct modifications to a given genome. Though in its infancy, maturation of this field will facilitate powerful new biomedical research approaches, and will enable a host of far-reaching biological engineering applications, including new therapeutic modalities and industrial applications, as well as 'genome writing' and de-extinction efforts. In this perspective, we focus on multiplex editing of large eukaryotic genomes. We describe the current state of multiplexed genome editing, the current limits of our ability to multiplex edits, and provide perspective on the many applications that fully-realized multiplex editing technologies would enable in higher eukaryotic genomes...
December 14, 2017: ACS Chemical Biology
Ava C Carter, Howard Y Chang, George Church, Ashley Dombkowski, Joseph R Ecker, Elad Gil, Paul G Giresi, Henry Greely, William J Greenleaf, Nir Hacohen, Chuan He, David Hill, Justin Ko, Isaac Kohane, Anshul Kundaje, Megan Palmer, Michael P Snyder, Joyce Tung, Alexander Urban, Marc Vidal, Wing Wong
No abstract text is available yet for this article.
December 8, 2017: Nature Biotechnology
Cody Church, George Mawko, John Paul Archambault, Robert Lewandowski, David Liu, Sharon Kehoe, Daniel Boyd, Robert Abraham, Alasdair Syme
PURPOSE: Radiopaque microspheres may provide intraprocedural and postprocedural feedback during transarterial radioembolization (TARE). Furthermore, the potential to use higher resolution x-ray imaging techniques as opposed to nuclear medicine imaging suggests that significant improvements in the accuracy and precision of radiation dosimetry calculations could be realized for this type of therapy. This study investigates the absorbed dose kernel for novel radiopaque microspheres including contributions of both short and long-lived contaminant radionuclides while concurrently quantifying the self-shielding of the glass network...
February 2018: Medical Physics
Isabella A Quakyi, George O Adjei, David J Sullivan, Judith K Stephens, Amos Laar, Vivian N Ama Aubyn, Richmond Owusu, Kwame S Sakyi, Nathaniel Coleman, Francis D Krampa, Linda Vanotoo, Julliette Tuakli, Bernard B Bortei, Edward Essuman, Felix Sorvor, Isaac A Boateng, Constance Bart-Plange, Ebenezer A Addison, Peter Winch, Andrew A Adjei
Background: Malaria is one of the most challenging public health concerns in the developing world. To address its impact in endemic regions, several interventions are implemented by stakeholders. The Affordable Medicine Facility-malaria (AMFm) is an example of such interventions. Its activities include communication interventions to enhance the knowledge of caregivers of children under five years, licensed chemical sellers (LCS) and prescribers on malaria management with artemisinin-based combination therapy (ACT)...
2017: Global Health Research and Policy
Xiaoyin Chen, Yu-Chi Sun, George M Church, Je Hyuk Lee, Anthony M Zador
Cellular DNA/RNA tags (barcodes) allow for multiplexed cell lineage tracing and neuronal projection mapping with cellular resolution. Conventional approaches to reading out cellular barcodes trade off spatial resolution with throughput. Bulk sequencing achieves high throughput but sacrifices spatial resolution, whereas manual cell picking has low throughput. In situ sequencing could potentially achieve both high spatial resolution and high throughput, but current in situ sequencing techniques are inefficient at reading out cellular barcodes...
November 28, 2017: Nucleic Acids Research
Marc Güell, Dong Niu, Yinan Kan, Haydy George, Tao Wang, I-Hsiu Lee, Gang Wang, George Church, Luhan Yang
No abstract text is available yet for this article.
November 2017: Xenotransplantation
Tessa Oraro, Nestor Ngube, George Yuh Atohmbom, Siddharth Srivastava, Kaspar Wyss
Within the existing health financing literature, males are typically categorized as the household's decision-makers. While this view accurately reflects many local sociocultural realities, approximately a quarter of sub-Saharan African households are now headed by females. In light of various efforts to expand health insurance coverage in the region, it is necessary to examine whether the factors influencing voluntary health insurance enrolment are analogous across male- and female-headed households. This study sought to identify the gendered determinants of voluntary enrolment into a church-run micro health insurance scheme...
November 13, 2017: Health Policy and Planning
George Church
Under normal circumstances, if you combined sperm half of which carried a dominant disease allele with unaffected oocytes, only 50% of the resulting human embryos would be expected to have unaffected copies of the gene in question. Researchers Ma, Mitalipov, and colleagues recently reported that..
November 16, 2017: New England Journal of Medicine
Marcus D Jarboe, Samir K Gadepalli, Joseph T Church, Meghan A Arnold, Ronald B Hirschl, George B Mychaliska
PURPOSE: The Avalon dual-lumen venovenous catheter has several advantages, but placement techniques and management have not been adequately addressed in the pediatric population. We assessed our institutional outcomes and complications using the Avalon catheter in children. METHODS: We reviewed all pediatric patients who had Avalon catheters placed for respiratory failure at our institution, excluding congenital heart disease patients, from April 2009 to March 2016...
October 12, 2017: Journal of Pediatric Surgery
Rebecca S Shapiro, Alejandro Chavez, Caroline B M Porter, Meagan Hamblin, Christian S Kaas, James E DiCarlo, Guisheng Zeng, Xiaoli Xu, Alexey V Revtovich, Natalia V Kirienko, Yue Wang, George M Church, James J Collins
Candida albicans is the leading cause of fungal infections; yet, complex genetic interaction analysis remains cumbersome in this diploid pathogen. Here, we developed a CRISPR-Cas9-based 'gene drive array' platform to facilitate efficient genetic analysis in C. albicans. In our system, a modified DNA donor molecule acts as a selfish genetic element, replaces the targeted site and propagates to replace additional wild-type loci. Using mating-competent C. albicans haploids, each carrying a different gene drive disabling a gene of interest, we are able to create diploid strains that are homozygous double-deletion mutants...
January 2018: Nature Microbiology
Samira Musah, Akiko Mammoto, Thomas C Ferrante, Sauveur S F Jeanty, Mariko Hirano-Kobayashi, Tadanori Mammoto, Kristen Roberts, Seyoon Chung, Richard Novak, Miles Ingram, Tohid Fatanat-Didar, Sandeep Koshy, James C Weaver, George M Church, Donald E Ingber
An in vitro model of the human kidney glomerulus - the major site of blood filtration - could facilitate drug discovery and illuminate kidney-disease mechanisms. Microfluidic organ-on-a-chip technology has been used to model the human proximal tubule, yet a kidney-glomerulus-on-a-chip has not been possible because of the lack of functional human podocytes - the cells that regulate selective permeability in the glomerulus. Here, we demonstrate an efficient (> 90%) and chemically defined method for directing the differentiation of human induced pluripotent stem (hiPS) cells into podocytes that express markers of the mature phenotype (nephrin+, WT1+, podocin+, Pax2-) and that exhibit primary and secondary foot processes...
2017: Nature Biomedical Engineering
Arin L Madenci, Joseph T Church, Robert J Gajarski, Kathryn Marchetti, Edwin J Klein, Megan A Coughlin, Jeannie Kreutzmann, Marjorie Treadwell, Maria Ladino-Torres, George B Mychaliska
No abstract text is available yet for this article.
October 16, 2017: European Journal of Pediatric Surgery
Jay Shendure, Shankar Balasubramanian, George M Church, Walter Gilbert, Jane Rogers, Jeffery A Schloss, Robert H Waterston
This review commemorates the 40th anniversary of DNA sequencing, a period in which we have already witnessed multiple technological revolutions and a growth in scale from a few kilobases to the first human genome, and now to millions of human and a myriad of other genomes. DNA sequencing has been extensively and creatively repurposed, including as a 'counter' for a vast range of molecular phenomena. We predict that in the long view of history, the impact of DNA sequencing will be on a par with that of the microscope...
October 19, 2017: Nature
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