scholarly journals Genomic and phenotypic analyses of six offspring of a genome-edited hornless bull

2019 ◽  
Vol 38 (2) ◽  
pp. 225-232 ◽  
Author(s):  
Amy E. Young ◽  
Tamer A. Mansour ◽  
Bret R. McNabb ◽  
Joseph R. Owen ◽  
Josephine F. Trott ◽  
...  
Keyword(s):  
Donor Plasmid ◽  
Genomic Alterations ◽  
Bioinformatics Analyses ◽  
The Public ◽  
Homology Directed Repair ◽  
Naturally Occurring ◽  
A Genome ◽  
Dairy Bulls ◽  
Illumina Hiseq4000 ◽  
Dairy Bull

Abstract Genome editing followed by reproductive cloning was previously used to produce two hornless dairy bulls. We crossed one genome-edited dairy bull, homozygous for the dominant PC Celtic POLLED allele, with horned cows (pp) and obtained six heterozygous (PCp) polled calves. The calves had no horns and were otherwise healthy and phenotypically unremarkable. We conducted whole-genome sequencing of all animals using an Illumina HiSeq4000 to achieve ~20× coverage. Bioinformatics analyses revealed the bull was a compound heterozygote, carrying one naturally occurring PC Celtic POLLED allele and an allele containing an additional introgression of the homology-directed repair donor plasmid along with the PC Celtic allele. These alleles segregated in the offspring of this bull, and inheritance of either allele produced polled calves. No other unintended genomic alterations were observed. These data can be used to inform conversations in the scientific community, with regulatory authorities and with the public around ‘intentional genomic alterations’ and future regulatory actions regarding genome-edited animals.

scholarly journals Mapping CRISPR-Cas9 public and commercial innovation using The Lens institutional toolkit

2021 ◽  
Author(s):  
Osmat Azzam Jefferson ◽  
Simon Lang ◽  
Kenny Williams ◽  
Deniz Koellhofer ◽  
Aaron Ballagh ◽  
...  
Keyword(s):  
Public Investment ◽  
Open Data ◽  
Regulatory Elements ◽  
Policy Makers ◽  
Base Editing ◽  
The Public ◽  
Homology Directed Repair ◽  
A Genome ◽  
Institutional Capability ◽  
Cellular Dna

AbstractCRISPR-Cas9 is a revolutionary technology because it is precise, fast and easy to implement, cheap and components are readily accessible. This versatility means that the technology can deliver a timely end product and can be used by many stakeholders. In plant cells, the technology can be applied to knockout genes by using CRISPR–Cas nucleases that can alter coding gene regions or regulatory elements, alter precisely a genome by base editing to delete or regulate gene expression, edit precisely a genome by homology-directed repair mechanism (cellular DNA), or regulate transcriptional machinery by using dead Cas proteins to recruit regulators to the promoter region of a gene. All these applications can be for: 1) Research use (Non commercial), 2) Uses related product components for the technology itself (reagents, equipment, toolkits, vectors etc), and 3) Uses related to the development and sale of derived end products based on this technology. In this contribution, we present a prototype report that can engage the community in open, inclusive and collaborative innovation mapping. Using the open data at the Lens.org platform and other relevant sources, we tracked, analyzed, organized, and assembled contextual and bridged patent and scholarly knowledge about CRISPR-Cas9 and with the assistance of a new Lens institutional capability, The Lens Report Builder, currently in beta release, mapped the public and commercial innovation pathways of the technology. When scaled, this capability will also enable coordinated editing and curation by credentialed experts to inform policy makers, businesses and private or public investment.

scholarly journals Evaluating the impact of exposure to environmental contaminants on human health

1996 ◽  
Vol 42 (8) ◽  
pp. 1345-1349 ◽  
Author(s):  
J B Silkworth ◽  
J F Brown
Keyword(s):  
Chemical Substances ◽  
The Public ◽  
Aromatic Hydrocarbon Receptor ◽  
Naturally Occurring ◽  
Synthetic Chemicals ◽  
Low Concentrations ◽  
Polycyclic Aromatic ◽  
Coplanar Polychlorinated Biphenyls ◽  
Proportional Contribution ◽  
The Impact

Abstract Humans are exposed daily to low concentrations of many different chemical substances, natural and some man-made. Although many of these substances can be toxic at high levels, typical exposures are far below the effect levels. The responses produced by man-made aromatic hydrocarbon receptor agonists, such as dioxins, polychlorinated dibenzofurans, coplanar polychlorinated biphenyls, and polycyclic aromatic hydrocarbons, are also produced, often to greater extents [corrected], by naturally occurring constituents of fried meat, cabbage, broccoli, cauliflower, cocoa, and curry. Our society seems to be concerned about the health risks associated only with the synthetic chemicals, regardless of their proportional contribution to the total agonist activity, and regulates on the basis of such concerns. It would be more protective of the public health to determine acceptable concentrations for each type of response, regardless of the origin of the inducing agent, and issue advisories or regulations accordingly.

scholarly journals Intramolecular phenotypic capacitance in a modular RNA molecule

2015 ◽  
Vol 112 (40) ◽  
pp. 12444-12449 ◽  
Author(s):  
Eric J. Hayden ◽  
Devin P. Bendixsen ◽  
Andreas Wagner
Keyword(s):  
Catalytic Activity ◽  
In Vitro Selection ◽  
Ion Concentration ◽  
Magnesium Ion ◽  
Interacting Protein ◽  
Genetic Changes ◽  
Low Magnesium ◽  
Naturally Occurring ◽  
A Genome

Phenotypic capacitance refers to the ability of a genome to accumulate mutations that are conditionally hidden and only reveal phenotype-altering effects after certain environmental or genetic changes. Capacitance has important implications for the evolution of novel forms and functions, but experimentally studied mechanisms behind capacitance are mostly limited to complex, multicomponent systems often involving several interacting protein molecules. Here we demonstrate phenotypic capacitance within a much simpler system, an individual RNA molecule with catalytic activity (ribozyme). This naturally occurring RNA molecule has a modular structure, where a scaffold module acts as an intramolecular chaperone that facilitates folding of a second catalytic module. Previous studies have shown that the scaffold module is not absolutely required for activity, but dramatically decreases the concentration of magnesium ions required for the formation of an active site. Here, we use an experimental perturbation of magnesium ion concentration that disrupts the folding of certain genetic variants of this ribozyme and use in vitro selection followed by deep sequencing to identify genotypes with altered phenotypes (catalytic activity). We identify multiple conditional mutations that alter the wild-type ribozyme phenotype under a stressful environmental condition of low magnesium ion concentration, but preserve the phenotype under more relaxed conditions. This conditional buffering is confined to the scaffold module, but controls the catalytic phenotype, demonstrating how modularity can enable phenotypic capacitance within a single macromolecule. RNA’s ancient role in life suggests that phenotypic capacitance may have influenced evolution since life’s origins.

scholarly journals Fundamentals of logic, reasoning, and argumentation: an evidence-supported curriculum targeting scientific literacy to increase public understanding and engagement in science

2020 ◽  
Vol 7 (1) ◽  
pp. 72
Author(s):  
La Shun L. Carroll
Keyword(s):  
Scientific Literacy ◽  
Public Understanding ◽  
Basic Knowledge ◽  
Public Confidence ◽  
Synthetic Approach ◽  
The Public ◽  
Naturally Occurring ◽  
Understanding Of Science ◽  
The Relationship ◽  
Logic Reasoning

<p>The purpose of this article is to present an evidence-supported curriculum covering the fundamentals of logic, reasoning, and argumentation skills to address the emphasized basic knowledge, skills, and abilities required to be scientifically literate, which will prepare the public to understand and engage with science meaningfully.  An analytic-synthetic approach toward understanding the notion of public is taken using a theoretical biomimetics framework that identifies naturally occurring objects or phenomena that descriptively captures the essence of a construct to facilitate creative problem- solving.  In the present case, the problem being solved is how to reconcile what is meant by public, how it ought to be interpreted, determining the diverse levels of confidence in science that exist, and various understandings of science all with one another.  The results demonstrate there is an inherent denotative-connotative inconsistency in the traditional notion of public that can be explicated through the concept of a fractal allowing for comprehension of the relationship between public confidence in, and understanding of, science.</p>

scholarly journals INCIPIENT GENOME DIFFERENTIATION IN GOSSYPIUM. III. COMPARISON OF CHROMOSOMES OF G. HIRSUTUM AND ASIATIC DIPLOIDS USING HETEROZYGOUS TRANSLOCATIONS

Genetics ◽  
1982 ◽  
Vol 100 (1) ◽  
pp. 89-103
Author(s):  
Margaret Y Menzel ◽  
Clare A Hasenkampf ◽  
James McD Stewart
Keyword(s):  
Upland Cotton ◽  
Diploid Species ◽  
Standard Line ◽  
Preferential Pairing ◽  
D Genome ◽  
Reciprocal Translocations ◽  
Genome Constitution ◽  
Naturally Occurring ◽  
A Genome ◽  
Segregation Ratios

ABSTRACT Hybrids between upland cotton (G. hirsutum, genome constitution 2AhDh) and either A-genome or D-genome diploid species exhibit 26 paired and 13 unpaired chromosomes at metaphase I. The Ah and Dh genomes are therefore considered homoeologous with those of the respective diploids. Previous studies, nevertheless, revealed a low level of ("incipient") differentiation between Dh and various diploid D genomes. The diploid A genomes have been regarded as more closely homologous to Ah on the basis of low preferential pairing and autotetraploid segregation ratios in allohexaploids.—The present study addressed the following questions: Are the diploid A genomes differentiated from Ah in meiotic homology? If so, is the differentiation manifested equally by all 13 chromosomes or is it localized in certain chromosomes?—Three diploid A-genome lines representing G. herbaceum and G. arboreum were hybridized by in ovulo culture of embryos (1) with a standard line of G. hirsutum, which differs from G. herbaceum by two and from G. arboreum by three naturally occurring reciprocal translocations involving chromosomes 1—5, and (2) with six lines homozygous for experimental translocations involving chromosomes 6, 7, 10, 11, 12 and 13. Chiasma frequencies in hybrids were compared with those in appropriate G. hirsutum controls. In every comparison overall chiasma frequencies were slightly lower in the hybrids. Therefore Ah appears to be differentiated from the diploid A genomes. No localized differentiation was detected in chromosomes marked by experimental translocations. The differentiation may be localized mainly in chromosomes 4 and 5.

Exemption Levels for the Recycling and Disposal of Residues With Enhanced Levels of Natural Radioactivity (TENORM) in Germany

2001 ◽  
Author(s):  
R. Barthel ◽  
W. Goldammer ◽  
M. Helming
Keyword(s):  
Radiation Exposure ◽  
Radiation Protection ◽  
The Public ◽  
Naturally Occurring ◽  
Activity Concentrations ◽  
Measurement Strategy ◽  
Naturally Occurring Radionuclides ◽  
Disposal Options ◽  
Mining Residues ◽  
Adequate Measurement

Abstract The new German Radiation Protection Ordinance contains for the first time a systematic framework of regulations protecting workers and the public against radiation exposures from residues of industrial and mining processes containing enhanced levels of naturally occurring radionuclides (TENORM). These regulations will satisfy the requirements of the European Council Directive 96/29/EURATOM and serve as a common basis for the radiation protection activities of the German states in this field. The consideration of exposures from materials containing naturally occurring radionuclides gains on this basis an increased level of significance within the German radiation protection efforts. The overall goal of the new regulations is to keep the additional effective dose for the population from the recycling and disposal of TENORM below 1 mSv/a. In order to achieve this objective, companies in which such residues arise have to carry out representative measurements of activity concentrations in these materials. If exemption levels defined in the new regulations are exceeded, restrictions on the recycling and disposal come into effect. These exemption levels are nuclide specific and distinguish between material types and different recycling and disposal options. This specific definition of exemption criteria serves the goal to minimise the number of companies and the amount of residues affected by the new regulations to the extent possible, focussing the efforts of operators and regulators to those materials having the potential to actually cause radiation exposure problems. The specific exemption criteria were derived on the basis of an analysis of typical amounts and activity concentrations of industrial and mining residues with enhanced radioactivity contents in Germany. In a second step, practically applied options for the recycling and disposal of these materials were investigated. On this basis, generic scenarios for the radiation exposure of the workforce and the public were defined and doses were estimated. All relevant pathways including possible long term effects (ground water) were considered in these analyses. Based on the 1 mSv/a criterion, a catalogue of relevant materials, potentially requiring radiation protection measures, was developed. For these materials the practically applied recycling or disposal options were grouped into categories, for which specific exemption levels were derived. The derivation of these criteria was based on realistic estimates of radiation exposure, for example taking into account the dilution of the residues with other materials in technological processes or during the disposal in landfills. The residues subject to the new regulations mostly arise in large quantities over extended periods of time. This leads to significant variations of radionuclide concentrations depending on feed materials and process parameters. To carry out representative measurements without the necessity of taking a too large number of samples, therefore, requires an adequate measurement strategy. Particular aspects to be considered are uncertainties of the measurements themselves and the heterogeneity of the residues. In addition, the measurement strategy has to be compatible with diverse situations in the different industries affected. The framework developed for designing individual strategies for the various industries and types of residues satisfies these requirements and can also provide guidance for measurement campaigns in other areas. The paper outlines the general situation with regard to TENORM in Germany. The main streams of residues and options for their recycling or disposal are described. On this basis, scenarios used for the radiological evaluation are defined and examples for resulting radiation exposures are given. The exemption levels derived from this analysis are discussed. Finally, the framework for the design and implementation of an adequate measurement strategy is outlined.

scholarly journals ICRP approach for radiological protection from NORM in industrial processes

2020 ◽  
Vol 49 (1_suppl) ◽  
pp. 84-97
Author(s):  
J.F. Lecomte
Keyword(s):  
Radioactive Material ◽  
Industrial Processes ◽  
Radiological Protection ◽  
Radiological Emergency ◽  
The Public ◽  
Protective Actions ◽  
Naturally Occurring ◽  
Radiological Hazards ◽  
Naturally Occurring Radioactive Material ◽  
Tissue Reactions

The International Commission on Radiological Protection (ICRP) recently issued ICRP Publication 142 on radiological protection from naturally occurring radioactive material (NORM) in industrial processes. Industries involving NORM may give rise to multiple hazards, and the radiological hazard is not necessarily dominant. They are diverse and may involve exposure of people and the environment where protective actions need to be considered. In some cases, there is a potential for significant routine exposure of workers and members of the public. Releases of large volumes of NORM may also result in detrimental effects on the environment from radiological and non-radiological constituents. However, industries involving NORM present no real prospect of a radiological emergency leading to tissue reactions or immediate danger for life. Radiological protection in these industries can be appropriately addressed on the basis of the principles of justification of the actions taken and optimisation of protection using reference levels. An integrated and graded approach is recommended for the protection of workers, the public, and the environment, where consideration of non-radiological hazards is integrated with the radiological hazards, and the approach to protection is optimised (graded) so that the use of various radiological protection programme elements is consistent with the hazards while not imposing unnecessary burdens.

Co-expression network analysis revealing the potential regulatory roles of lncRNAs in atrial fibrillation

2019 ◽  
Vol 14 ◽  
Author(s):  
Lishui Shen ◽  
Guilin Shen ◽  
Xiaoli Lu ◽  
Guomin Ding ◽  
Xiaofeng Hu
Keyword(s):  
Atrial Fibrillation ◽  
Differentially Expressed ◽  
Biological Processes ◽  
Bioinformatics Analyses ◽  
The Public ◽  
Kegg Pathway Analysis ◽  
Novel Biomarkers ◽  
Non Coding Rnas ◽  
Public Datasets ◽  
Insight Into

Atrial fibrillation (AF) is one of the most common heart arrhythmic disorders all over the world. However, it is worth noting that the mechanism underlying AF is still dimness. In this study, we implemented a series of bioinformatics methods to explore the mechanisms of lncRNAs underlying AF pathogenesis. The present study analyzed the public datasets (GSE2240 and GSE115574) to identify differentially expressed long non-coding RNAs (lncRNAs) and mRNAs in the progression of AF. Totally, 71 differentially expressed lncRNAs and 390 DEGs were identified in AF.Next, we performed bioinformatics analyses to explore the functions of lncRNAs in AF. Gene Ontology (GO) analysis indicated that differentially expressed lncRNAs were involved in regulating multiple key biological processes, such as cell cycle and signal transduction. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis demonstrated these lncRNAs were associated with the regulation of MAPK and Wnt signaling pathways. Eight lncRNAs (RP5-1154L15.2, RP11-339B21.15, RP11-448A19.1, RP11-676J12.4, LOC101930415, MALAT1, NEAT1, and PWAR6) were identified to be key lncRNAs and widely co-expressed with a series of differentially expressed genes (DEGs). Although further validation was still needed, our study may be helpful to elucidate the mechanisms of lncRNAs underlying AF pathogenesis and providing further insight into identifying novel biomarkers for AF.

Accelerating Biomedical Research through Semantic Web Services

2016 ◽  
pp. 2385-2401
Author(s):  
Artemis Chaleplioglou
Keyword(s):  
Web Services ◽  
Semantic Web ◽  
Biomedical Research ◽  
Semantic Web Services ◽  
Biomedical Data ◽  
Healthcare Outcomes ◽  
Bioinformatics Analyses ◽  
The Public ◽  
Meaningful Relationships ◽  
Machine Readable

In view of the fact that there is a lot of biomedical research data, rapidly accumulating to relevant repositories, there is an urgent need these data to be delivered, as soon as possible, to the specific scientific audience interesting in it. Unfortunately, the current database technologies often isolate data rather than making it easily and freely accessible. A considerable effort by the information scientists is needed to process the resources that meet the scientific query criteria as well as to index and present them as useful metadata. Taking into account that biomedical data are mostly hidden from the public eye, often stored in not indexed databases or libraries and inaccessible by standard search engines, the retrieval, storing, annotating, and qualification of health information remain major challenges. The evolution of the World Wide Web from a collection of unstructured and predominantly human readable data into the Semantic Web of knowledge with meaningful relationships between resources and machine readable data will significantly improve our ability to conduct bioinformatics analyses and to make better clinical decisions that positively affect healthcare outcomes. To this end novel semantic web services arise, which depend on markup ontologies in order to make biological and clinical data logical analysis computational and reasonable processed through the utilization of appropriate algorithms. Herein, we discuss the use of these technologies for the efficient and reliable retrieval of meaningful biomedical data from the relevant resources and repositories.

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