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https://www.readbyqxmd.com/read/28435878/evolutionary-dynamics-of-crispr-gene-drives
#1
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
#2
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
#3
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
#4
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
#5
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
https://www.readbyqxmd.com/read/28264712/erratum-to-the-gut-microbiota-in-conventional-and-serrated-precursors-of-colorectal-cancer
#6
Brandilyn A Peters, Christine Dominianni, Jean A Shapiro, Timothy R Church, Jing Wu, George Miller, Elizabeth Yuen, Hal Freiman, Ian Lustbader, James Salik, Charles Friedlander, Richard B Hayes, Jiyoung Ahn
No abstract text is available yet for this article.
March 6, 2017: Microbiome
https://www.readbyqxmd.com/read/28259369/delayed-hematologic-toxicity-following-rattlesnake-envenomation-unresponsive-to-crotalidae-polyvalent-antivenom
#7
Abby M Bailey, Stephanie Justice, George A Davis, Kyle Weant
North American rattlesnake envenomations are known to produce coagulopathies and thrombocytopenia. However, the occurrence of delayed hematologic toxicity (less than seven days after envenomation) is poorly characterized in the medical literature. While the recurrence of hematologic derangements has been documented following envenomation, it is usually in the absence of clinically significant bleeding. Although commonly recommended to treat delayed coagulopathies, the effectiveness of crotalidae polyvalent immune Fab ovine (CroFab®) in managing this condition remains in question and warrants further investigation and exploration...
February 27, 2017: American Journal of Emergency Medicine
https://www.readbyqxmd.com/read/28231060/improving-quality-in-the-preanalytical-phase-through-innovation-on-behalf-of-the-european-federation-for-clinical-chemistry-and-laboratory-medicine-eflm-working-group-for-preanalytical-phase-wg-pre
#8
Giuseppe Lippi, Geoffrey S Baird, Giuseppe Banfi, Karin Bölenius, Janne Cadamuro, Stephen Church, Michael P Cornes, Anna Dacey, Antoine Guillon, Georg Hoffmann, Mads Nybo, Lakdasa Devananda Premawardhana, María Salinas, Sverre Sandberg, Robbert Slingerland, Ana Stankovic, Sylte Marit Sverresdotter, Pieter Vermeersch, Ana-Maria Simundic
It is now undeniable that laboratory testing is vital for the diagnosis, prognostication and therapeutic monitoring of human disease. Despite the many advances made for achieving a high degree of quality and safety in the analytical part of diagnostic testing, many hurdles in the total testing process remain, especially in the preanalytical phase ranging from test ordering to obtaining and managing the biological specimens. The Working Group for the Preanalytical Phase (WG-PRE) of the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) has planned many activities aimed at mitigating the vulnerability of the preanalytical phase, including the organization of three European meetings in the past 7 years...
March 1, 2017: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/28165460/programmable-transcriptional-repression-in-mycobacteria-using-an-orthogonal-crispr-interference-platform
#9
Jeremy M Rock, Forrest F Hopkins, Alejandro Chavez, Marieme Diallo, Michael R Chase, Elias R Gerrick, Justin R Pritchard, George M Church, Eric J Rubin, Christopher M Sassetti, Dirk Schnappinger, Sarah M Fortune
The development of new drug regimens that allow rapid, sterilizing treatment of tuberculosis has been limited by the complexity and time required for genetic manipulations in Mycobacterium tuberculosis. CRISPR interference (CRISPRi) promises to be a robust, easily engineered and scalable platform for regulated gene silencing. However, in M. tuberculosis, the existing Streptococcus pyogenes Cas9-based CRISPRi system is of limited utility because of relatively poor knockdown efficiency and proteotoxicity. To address these limitations, we screened eleven diverse Cas9 orthologues and identified four that are broadly functional for targeted gene knockdown in mycobacteria...
February 6, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28146356/sgrna-scorer-2-0-a-species-independent-model-to-predict-crispr-cas9-activity
#10
Raj Chari, Nan Cher Yeo, Alejandro Chavez, George M Church
It has been possible to create tools to predict single guide RNA (sgRNA) activity in the CRISPR/Cas9 system derived from Streptococcus pyogenes due to the large amount of data that has been generated in sgRNA library screens. However, with the discovery of additional CRISPR systems from different bacteria, which show potent activity in eukaryotic cells, the approach of generating large data sets for each of these systems to predict their activity is not tractable. Here, we present a new guide RNA tool that can predict sgRNA activity across multiple CRISPR systems...
February 10, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28038683/the-gut-microbiota-in-conventional-and-serrated-precursors-of-colorectal-cancer
#11
Brandilyn A Peters, Christine Dominianni, Jean A Shapiro, Timothy R Church, Jing Wu, George Miller, Elizabeth Yuen, Hal Freiman, Ian Lustbader, James Salik, Charles Friedlander, Richard B Hayes, Jiyoung Ahn
BACKGROUND: Colorectal cancer is a heterogeneous disease arising from at least two precursors-the conventional adenoma (CA) and the serrated polyp. We and others have previously shown a relationship between the human gut microbiota and colorectal cancer; however, its relationship to the different early precursors of colorectal cancer is understudied. We tested, for the first time, the relationship of the gut microbiota to specific colorectal polyp types. RESULTS: Gut microbiota were assessed in 540 colonoscopy-screened adults by 16S rRNA gene sequencing of stool samples...
December 30, 2016: Microbiome
https://www.readbyqxmd.com/read/27984456/developing-a-clinical-protocol-for-habitual-physical-activity-monitoring-in-youth-with-cerebral-palsy
#12
Kristen Nicholson, Aaron Weaver, Ameeka George, Robert Hulbert, Chris Church, Nancy Lennon
PURPOSE: The StepWatch (SW) has been used to monitor physical activity (PA) in youth with cerebral palsy; however, there is no standard collection protocol. The goal was to develop such a protocol. METHODS: Data were examined from patients who wore the SW for 8 to 14 days. The Spearman-Brown prediction formula determined the minimum number of days for reliable PA. Weekdays were compared to weekends and 10- and 60-second collection intervals were examined. RESULTS: The PA data were collected from 98 youth with cerebral palsy...
January 2017: Pediatric Physical Therapy
https://www.readbyqxmd.com/read/27929521/efficient-footprint-free-human-ipsc-genome-editing-by-consolidation-of-cas9-crispr-and-piggybac-technologies
#13
Gang Wang, Luhan Yang, Dennis Grishin, Xavier Rios, Lillian Y Ye, Yong Hu, Kai Li, Donghui Zhang, George M Church, William T Pu
Genome editing of human induced pluripotent stem cells (hiPSCs) offers unprecedented opportunities for in vitro disease modeling and personalized cell replacement therapy. The introduction of Cas9-directed genome editing has expanded adoption of this approach. However, marker-free genome editing using standard protocols remains inefficient, yielding desired targeted alleles at a rate of ∼1-5%. We developed a protocol based on a doxycycline-inducible Cas9 transgene carried on a piggyBac transposon to enable robust and highly efficient Cas9-directed genome editing, so that a parental line can be expeditiously engineered to harbor many separate mutations...
January 2017: Nature Protocols
https://www.readbyqxmd.com/read/27918539/rapidly-evolving-homing-crispr-barcodes
#14
Reza Kalhor, Prashant Mali, George M Church
We present an approach for engineering evolving DNA barcodes in living cells. A homing guide RNA (hgRNA) scaffold directs the Cas9-hgRNA complex to the DNA locus of the hgRNA itself. We show that this homing CRISPR-Cas9 system acts as an expressed genetic barcode that diversifies its sequence and that the rate of diversification can be controlled in cultured cells. We further evaluate these barcodes in cell populations and show that they can be used to record lineage history and that the barcode RNA can be amplified in situ, a prerequisite for in situ sequencing...
February 2017: Nature Methods
https://www.readbyqxmd.com/read/27909236/sexual-risk-behaviors-of-african-american-adolescent-females-the-role-of-cognitive-and-religious-factors
#15
Safiya George Dalmida, Natasha Aduloju-Ajijola, Dora Clayton-Jones, Tami L Thomas, Ricardo J Erazo Toscano, Rashunda Lewis, Terri Fleming, Shirley Taylor, Macie Lunyong
INTRODUCTION: African American (AA) high school-age girls are more likely to have had sex before age 13 years and have higher rates of all sexually transmitted infections. Cognition and religion/spirituality are associated with adolescent sexuality, therefore, the purpose of this study was to identify cognitive and religious substrates of AA girls' risky sexual behaviors. METHOD: A descriptive study was conducted with 65 AA girls aged 15 to 20 years using computerized questionnaires and cognitive function tasks...
November 30, 2016: Journal of Transcultural Nursing: Official Journal of the Transcultural Nursing Society
https://www.readbyqxmd.com/read/27888789/reliability-and-minimal-detectable-change-in-foot-pressure-measurements-in-typically-developing-children
#16
Timothy Niiler, Chris Church, Nancy Lennon, John Henley, Ameeka George, Daveda Taylor, Angelica Montes, Freeman Miller
BACKGROUND: In pedobarography, clinically meaningful comparison of measurements within or between subjects is limited by data variability and measurement error. This study aims to determine the components of the minimal detectable change (MDC) in impulse across all foot regions and the reliability of these measures. METHODS: A convenience sample of foot pressures from 108 visits by normal, healthy subjects aged 2-17 years was studied. Each subject had three pedobarograph measurements taken per foot, with six subjects returning for a second visit for assessment of day-to-day variability...
December 2016: Foot
https://www.readbyqxmd.com/read/27882922/an-ethnically-relevant-consensus-korean-reference-genome-is-a-step-towards-personal-reference-genomes
#17
Yun Sung Cho, Hyunho Kim, Hak-Min Kim, Sungwoong Jho, JeHoon Jun, Yong Joo Lee, Kyun Shik Chae, Chang Geun Kim, Sangsoo Kim, Anders Eriksson, Jeremy S Edwards, Semin Lee, Byung Chul Kim, Andrea Manica, Tae-Kwang Oh, George M Church, Jong Bhak
Human genomes are routinely compared against a universal reference. However, this strategy could miss population-specific and personal genomic variations, which may be detected more efficiently using an ethnically relevant or personal reference. Here we report a hybrid assembly of a Korean reference genome (KOREF) for constructing personal and ethnic references by combining sequencing and mapping methods. We also build its consensus variome reference, providing information on millions of variants from 40 additional ethnically homogeneous genomes from the Korean Personal Genome Project...
November 24, 2016: Nature Communications
https://www.readbyqxmd.com/read/27804970/engineering-and-optimising-deaminase-fusions-for-genome-editing
#18
Luhan Yang, Adrian W Briggs, Wei Leong Chew, Prashant Mali, Marc Guell, John Aach, Daniel Bryan Goodman, David Cox, Yinan Kan, Emal Lesha, Venkataramanan Soundararajan, Feng Zhang, George Church
Precise editing is essential for biomedical research and gene therapy. Yet, homology-directed genome modification is limited by the requirements for genomic lesions, homology donors and the endogenous DNA repair machinery. Here we engineered programmable cytidine deaminases and test if we could introduce site-specific cytidine to thymidine transitions in the absence of targeted genomic lesions. Our programmable deaminases effectively convert specific cytidines to thymidines with 13% efficiency in Escherichia coli and 2...
November 2, 2016: Nature Communications
https://www.readbyqxmd.com/read/27782796/complete-mitochondrial-genomes-of-living-and-extinct-pigeons-revise-the-timing-of-the-columbiform-radiation
#19
André E R Soares, Ben J Novak, James Haile, Tim H Heupink, Jon Fjeldså, M Thomas P Gilbert, Hendrik Poinar, George M Church, Beth Shapiro
BACKGROUND: Pigeons and doves (Columbiformes) are one of the oldest and most diverse extant lineages of birds. However, the nature and timing of the group's evolutionary radiation remains poorly resolved, despite recent advances in DNA sequencing and assembly and the growing database of pigeon mitochondrial genomes. One challenge has been to generate comparative data from the large number of extinct pigeon lineages, some of which are morphologically unique and therefore difficult to place in a phylogenetic context...
October 26, 2016: BMC Evolutionary Biology
https://www.readbyqxmd.com/read/27730198/a-randomised-open-label-study-of-umeclidinium-versus-glycopyrronium-in-patients-with-copd
#20
Tara Rheault, Sanjeev Khindri, Mitra Vahdati-Bolouri, Alison Church, William A Fahy
This study compared the efficacy and safety of once-daily umeclidinium 62.5 µg with once-daily glycopyrronium 50 µg in patients with moderate-to-severe chronic obstructive pulmonary disease. This was a 12-week, multicentre, randomised, open-label, parallel-group study (Clinicaltrials.gov: NCT02236611). Patients were randomised 1:1 to umeclidinium 62.5 µg or glycopyrronium 50 µg administered via Ellipta or Breezhaler dry powder inhaler, respectively. The primary endpoint was trough forced expiratory volume in 1 s (FEV1) at day 85 in the per-protocol population...
April 2016: ERJ Open Research
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