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George Church

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https://www.readbyqxmd.com/read/28798043/inactivation-of-porcine-endogenous-retrovirus-in-pigs-using-crispr-cas9
#1
Dong Niu, Hong-Jiang Wei, Lin Lin, Haydy George, Tao Wang, I-Hsiu Lee, Hong-Ye Zhao, Yong Wang, Yinan Kan, Ellen Shrock, Emal Lesha, Gang Wang, Yonglun Luo, Yubo Qing, Deling Jiao, Heng Zhao, Xiaoyang Zhou, Shouqi Wang, Hong Wei, Marc Güell, George M Church, Luhan Yang
Xenotransplantation is a promising strategy to alleviate the shortage of organs for human transplantation. In addition to the concern on pig-to-human immunological compatibility, the risk of cross-species transmission of porcine endogenous retroviruses (PERVs) has impeded the clinical application of this approach. Earlier, we demonstrated the feasibility of inactivating PERV activity in an immortalized pig cell line. Here, we confirmed that PERVs infect human cells, and observed the horizontal transfer of PERVs among human cells...
August 10, 2017: Science
https://www.readbyqxmd.com/read/28714951/rates-distribution-and-implications-of-postzygotic-mosaic-mutations-in-autism-spectrum-disorder
#2
Elaine T Lim, Mohammed Uddin, Silvia De Rubeis, Yingleong Chan, Anne S Kamumbu, Xiaochang Zhang, Alissa M D'Gama, Sonia N Kim, Robert Sean Hill, Arthur P Goldberg, Christopher Poultney, Nancy J Minshew, Itaru Kushima, Branko Aleksic, Norio Ozaki, Mara Parellada, Celso Arango, Maria J Penzol, Angel Carracedo, Alexander Kolevzon, Christina M Hultman, Lauren A Weiss, Menachem Fromer, Andreas G Chiocchetti, Christine M Freitag, George M Church, Stephen W Scherer, Joseph D Buxbaum, Christopher A Walsh
We systematically analyzed postzygotic mutations (PZMs) in whole-exome sequences from the largest collection of trios (5,947) with autism spectrum disorder (ASD) available, including 282 unpublished trios, and performed resequencing using multiple independent technologies. We identified 7.5% of de novo mutations as PZMs, 83.3% of which were not described in previous studies. Damaging, nonsynonymous PZMs within critical exons of prenatally expressed genes were more common in ASD probands than controls (P < 1 × 10(-6)), and genes carrying these PZMs were enriched for expression in the amygdala (P = 5...
July 17, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28707856/science-and-orthodox-christianity-an-overview
#3
Efthymios Nicolaidis, Eudoxie Delli, Nikolaos Livanos, Kostas Tampakis, George Vlahakis
This essay offers an overview of the history of the relations between science and Eastern Christianity based on Greek-language sources. The civilizations concerned are the Byzantine Empire, the Christian Orthodox communities of the Ottoman Empire, and modern Greece, as a case study of a national state. Beginning with the Greek Church Fathers, the essay investigates the ideas of theologians and scholars on nature. Neoplatonism, the theological debates of Iconoclasm and Hesychasm, the proposed union of the Eastern and Western Churches, and the complex relations with the Hellenic past all had notable impacts on the conception of science held by the Byzantine Orthodox...
September 2016: Isis; An International Review Devoted to the History of Science and its Cultural Influences
https://www.readbyqxmd.com/read/28702280/dissecting-limiting-factors-of-the-protein-synthesis-using-recombinant-elements-pure-system
#4
Jun Li, Chi Zhang, Poyi Huang, Erkin Kuru, Eliot T C Forster-Benson, Taibo Li, George M Church
Reconstituted cell-free protein synthesis systems such as the Protein synthesis Using Recombinant Elements (PURE) system give high-throughput and controlled access to in vitro protein synthesis. Here we show that compared with the commercial S30 crude extract based RTS 100 E. coli HY system, the PURE system has less mRNA degradation and produces up to ∼6-fold full-length proteins. However the majority of polypeptides PURE produces are partially translated or inactive since the signal from firefly luciferase (Fluc) translated in PURE is only ∼2/3(rd) of that measured using the RTS 100 E...
2017: Translation
https://www.readbyqxmd.com/read/28700573/crispr-cas-encoding-of-a-digital-movie-into-the-genomes-of-a-population-of-living-bacteria
#5
Seth L Shipman, Jeff Nivala, Jeffrey D Macklis, George M Church
DNA is an excellent medium for archiving data. Recent efforts have illustrated the potential for information storage in DNA using synthesized oligonucleotides assembled in vitro. A relatively unexplored avenue of information storage in DNA is the ability to write information into the genome of a living cell by the addition of nucleotides over time. Using the Cas1-Cas2 integrase, the CRISPR-Cas microbial immune system stores the nucleotide content of invading viruses to confer adaptive immunity. When harnessed, this system has the potential to write arbitrary information into the genome...
July 20, 2017: Nature
https://www.readbyqxmd.com/read/28591112/the-promise-of-organ-and-tissue-preservation-to-transform-medicine
#6
Sebastian Giwa, Jedediah K Lewis, Luis Alvarez, Robert Langer, Alvin E Roth, George M Church, James F Markmann, David H Sachs, Anil Chandraker, Jason A Wertheim, Martine Rothblatt, Edward S Boyden, Elling Eidbo, W P Andrew Lee, Bohdan Pomahac, Gerald Brandacher, David M Weinstock, Gloria Elliott, David Nelson, Jason P Acker, Korkut Uygun, Boris Schmalz, Brad P Weegman, Alessandro Tocchio, Greg M Fahy, Kenneth B Storey, Boris Rubinsky, John Bischof, Janet A W Elliott, Teresa K Woodruff, G John Morris, Utkan Demirci, Kelvin G M Brockbank, Erik J Woods, Robert N Ben, John G Baust, Dayong Gao, Barry Fuller, Yoed Rabin, David C Kravitz, Michael J Taylor, Mehmet Toner
The ability to replace organs and tissues on demand could save or improve millions of lives each year globally and create public health benefits on par with curing cancer. Unmet needs for organ and tissue preservation place enormous logistical limitations on transplantation, regenerative medicine, drug discovery, and a variety of rapidly advancing areas spanning biomedicine. A growing coalition of researchers, clinicians, advocacy organizations, academic institutions, and other stakeholders has assembled to address the unmet need for preservation advances, outlining remaining challenges and identifying areas of underinvestment and untapped opportunities...
June 7, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28569062/scalable-device-for-automated-microbial-electroporation-in-a-digital-microfluidic-platform
#7
Andrew C Madison, Matthew W Royal, Frederic Vigneault, Liji Chen, Peter B Griffin, Mark Horowitz, George M Church, Richard B Fair
Electrowetting-on-dielectric (EWD) digital microfluidic laboratory-on-a-chip platforms demonstrate excellent performance in automating labor-intensive protocols. When coupled with an on-chip electroporation capability, these systems hold promise for streamlining cumbersome processes such as multiplex automated genome engineering (MAGE). We integrated a single Ti:Au electroporation electrode into an otherwise standard parallel-plate EWD geometry to enable high-efficiency transformation of Escherichia coli with reporter plasmid DNA in a 200 nL droplet...
June 7, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28559321/qnas-with-alta-charo-and-george-church
#8
Prashant Nair
No abstract text is available yet for this article.
June 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28545559/millstone-software-for-multiplex-microbial-genome-analysis-and-engineering
#9
Daniel B Goodman, Gleb Kuznetsov, Marc J Lajoie, Brian W Ahern, Michael G Napolitano, Kevin Y Chen, Changping Chen, George M Church
Inexpensive DNA sequencing and advances in genome editing have made computational analysis a major rate-limiting step in adaptive laboratory evolution and microbial genome engineering. We describe Millstone, a web-based platform that automates genotype comparison and visualization for projects with up to hundreds of genomic samples. To enable iterative genome engineering, Millstone allows users to design oligonucleotide libraries and create successive versions of reference genomes. Millstone is open source and easily deployable to a cloud platform, local cluster, or desktop, making it a scalable solution for any lab...
May 25, 2017: Genome Biology
https://www.readbyqxmd.com/read/28545477/optimizing-complex-phenotypes-through-model-guided-multiplex-genome-engineering
#10
Gleb Kuznetsov, Daniel B Goodman, Gabriel T Filsinger, Matthieu Landon, Nadin Rohland, John Aach, Marc J Lajoie, George M Church
We present a method for identifying genomic modifications that optimize a complex phenotype through multiplex genome engineering and predictive modeling. We apply our method to identify six single nucleotide mutations that recover 59% of the fitness defect exhibited by the 63-codon E. coli strain C321.∆A. By introducing targeted combinations of changes in multiplex we generate rich genotypic and phenotypic diversity and characterize clones using whole-genome sequencing and doubling time measurements. Regularized multivariate linear regression accurately quantifies individual allelic effects and overcomes bias from hitchhiking mutations and context-dependence of genome editing efficiency that would confound other strategies...
May 25, 2017: Genome Biology
https://www.readbyqxmd.com/read/28544481/matching-phenotypes-to-whole-genomes-lessons-learned-from-four-iterations-of-the-personal-genome-project-community-challenges
#11
Binghuang Cai, Biao Li, Nikki Kiga, Janita Thusberg, Timothy Bergquist, Yun-Ching Chen, Noushin Niknafs, Hannah Carter, Collin Tokheim, Violeta Beleva-Guthrie, Christopher Douville, Rohit Bhattacharya, Hui Ting Grace Yeo, Jean Fan, Sohini Sengupta, Dewey Kim, Melissa Cline, Tychele Turner, Mark Diekhans, Jan Zaucha, Lipika R Pal, Chen Cao, Chen-Hsin Yu, Yizhou Yin, Marco Carraro, Manuel Giollo, Carlo Ferrari, Emanuela Leonardi, Silvio C E Tosatto, Jason Bobe, Madeleine Ball, Roger A Hoskins, Susanna Repo, George Church, Steven E Brenner, John Moult, Julian Gough, Mario Stanke, Rachel Karchin, Sean D Mooney
The advent of next-generation sequencing has dramatically decreased the cost for whole-genome sequencing and increased the viability for its application in research and clinical care. The Personal Genome Project (PGP) provides unrestricted access to genomes of individuals and their associated phenotypes. This resource enabled the Critical Assessment of Genome Interpretation (CAGI) to create a community challenge to assess the bioinformatics community's ability to predict traits from whole genomes. In the CAGI PGP challenge, researchers were asked to predict whether an individual had a particular trait or profile based on their whole genome...
May 23, 2017: Human Mutation
https://www.readbyqxmd.com/read/28494857/correction-addressing-the-ethical-issues-raised-by-synthetic-human-entities-with-embryo-like-features
#12
John Aach, Jeantine Lunshof, Eswar Iyer, George M Church
No abstract text is available yet for this article.
April 13, 2017: ELife
https://www.readbyqxmd.com/read/28494856/addressing-the-ethical-issues-raised-by-synthetic-human-entities-with-embryo-like-features
#13
John Aach, Jeantine Lunshof, Eswar Iyer, George M Church
The "14-day rule" for embryo research stipulates that experiments with intact human embryos must not allow them to develop beyond 14 days or the appearance of the primitive streak. However, recent experiments showing that suitably cultured human pluripotent stem cells can self-organize and recapitulate embryonic features have highlighted difficulties with the 14-day rule and led to calls for its reassessment. Here we argue that these and related experiments raise more foundational issues that cannot be fixed by adjusting the 14-day rule, because the framework underlying the rule cannot adequately describe the ways by which synthetic human entities with embryo-like features (SHEEFs) might develop morally concerning features through altered forms of development...
March 21, 2017: ELife
https://www.readbyqxmd.com/read/28470971/impact-of-integrated-services-on-hiv-testing-a-nonrandomized-trial-among-kenyan-family-planning-clients
#14
Kathryn Church, Charlotte E Warren, Isolde Birdthistle, George B Ploubidis, Keith Tomlin, Weiwei Zhou, James Kimani, Timothy Abuya, Charity Ndwiga, Sedona Sweeney, Susannah H Mayhew
The impact of integrated reproductive health and HIV services on HIV testing and counseling (HTC) uptake was assessed among 882 Kenyan family planning clients using a nonrandomized cohort design within six intervention and six "comparison" facilities. The effect of integration on HTC goals (two tests over two years) was assessed using conditional logistic regression to test four "integration" exposures: a training and reorganization intervention; receipt of reproductive health and HIV services at recruitment; a functional measure of facility integration at recruitment; and a woman's cumulative exposure to functionally integrated care across different facilities over time...
June 2017: Studies in Family Planning
https://www.readbyqxmd.com/read/28459860/nucleotide-time-alignment-for-molecular-recorders
#15
Thaddeus R Cybulski, Edward S Boyden, George M Church, Keith E J Tyo, Konrad P Kording
Using a DNA polymerase to record intracellular calcium levels has been proposed as a novel neural recording technique, promising massive-scale, single-cell resolution monitoring of large portions of the brain. This technique relies on local storage of neural activity in strands of DNA, followed by offline analysis of that DNA. In simple implementations of this scheme, the time when each nucleotide was written cannot be determined directly by post-hoc DNA sequencing; the timing data must be estimated instead...
May 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28435878/evolutionary-dynamics-of-crispr-gene-drives
#16
Charleston Noble, Jason Olejarz, Kevin M Esvelt, George M Church, Martin A Nowak
The alteration of wild populations has been discussed as a solution to a number of humanity's most pressing ecological and public health concerns. Enabled by the recent revolution in genome editing, clustered regularly interspaced short palindromic repeats (CRISPR) gene drives-selfish genetic elements that can spread through populations even if they confer no advantage to their host organism-are rapidly emerging as the most promising approach. However, before real-world applications are considered, it is imperative to develop a clear understanding of the outcomes of drive release in nature...
April 2017: Science Advances
https://www.readbyqxmd.com/read/28387241/an-unbiased-index-to-quantify-participant-s-phenotypic-contribution-to-an-open-access-cohort
#17
Yingleong Chan, Michael Tung, Alexander S Garruss, Sarah W Zaranek, Ying Kai Chan, Jeantine E Lunshof, Alexander W Zaranek, Madeleine P Ball, Michael F Chou, Elaine T Lim, George M Church
The Personal Genome Project (PGP) is an effort to enroll many participants to create an open-access repository of genome, health and trait data for research. However, PGP participants are not enrolled for studying any specific traits and participants choose the phenotypes to disclose. To measure the extent and willingness and to encourage and guide participants to contribute phenotypes, we developed an algorithm to score and rank the phenotypes and participants of the PGP. The scoring algorithm calculates the participation index (P-index) for every participant, where 0 indicates no reported phenotypes and 100 indicate complete phenotype reporting...
April 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28365109/pushing-the-boundaries-of-ecls-outcomes-in-34-week-ega-neonates
#18
Joseph T Church, Anne C Kim, Kimberly M Erickson, Ankur Rana, Robert Drongowski, Ronald B Hirschl, Robert H Bartlett, George B Mychaliska
PURPOSE: Extracorporeal life support (ECLS) is usually reserved for infants ≥34weeks estimated gestational age (EGA) owing to concerns about increased mortality and incidence of intracranial hemorrhage (ICH). We sought to characterize survival, rates of ICH, and complications in <34week EGA neonates placed on ECLS. METHODS: 752 neonates of EGA 29-34weeks were identified in the Extracorporeal Life Support Organization (ELSO) Registry (1976-2008). Data analyzed included birthweight, survival, pre-ECLS conditions, ventilatory parameters and complications (including ICH and other neurological outcomes)...
March 27, 2017: Journal of Pediatric Surgery
https://www.readbyqxmd.com/read/28330337/cogenerating-synthetic-parts-toward-a-self-replicating-system
#19
Jun Li, Wilhelm Haas, Kirsten Jackson, Erkin Kuru, Michael C Jewett, Z Hugh Fan, Steven Gygi, George M Church
To build replicating systems with new functions, the engineering of existing biological machineries requires a sensible strategy. Protein synthesis Using Recombinant Elements (PURE) system consists of the desired components for transcription, translation, aminoacylation and energy regeneration. PURE might be the basis for a radically alterable, lifelike system after optimization. Here, we regenerated 54 E. coli ribosomal (r-) proteins individually from DNA templates in the PURE system. We show that using stable isotope labeling with amino acids, mass spectrometry based quantitative proteomics could detect 26 of the 33 50S and 20 of the 21 30S subunit r-proteins when coexpressed in batch format PURE system...
March 29, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28280319/umeclidinium-vilanterol-as-step-up-therapy-from-tiotropium-in-patients-with-moderate-copd-a-randomized-parallel-group-12-week-study
#20
Edward M Kerwin, Chris J Kalberg, Dmitry V Galkin, Chang-Qing Zhu, Alison Church, John H Riley, William A Fahy
INTRODUCTION: Patients with COPD who remain symptomatic on long-acting bronchodilator monotherapy may benefit from step-up therapy to a long-acting bronchodilator combination. This study evaluated the efficacy and safety of umeclidinium (UMEC)/vilanterol (VI) in patients with moderate COPD who remained symptomatic on tiotropium (TIO). METHODS: In this randomized, blinded, double-dummy, parallel-group study (NCT01899742), patients (N=494) who were prescribed TIO for ≥3 months at screening (forced expiratory volume in 1 s [FEV1]: 50%-70% of predicted; modified Medical Research Council [mMRC] score ≥1) and completed a 4-week run-in with TIO were randomized to UMEC/VI 62...
2017: International Journal of Chronic Obstructive Pulmonary Disease
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