Browsing by Subject "Biotechnology"

Now showing 1 - 10 of 22
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    Beyond therapy: biotechnology and the pursuit of happiness
    (2003-10) President’s Council on Bioethics (U.S.)
    Discusses the ethical issues involved with using biotechnology for human enhancement. "Among the biotechnical powers considered are techniques for screening genes and testing embryos, choosing sex of children, modifying the behavior of children, augmenting muscle size and strength, enhancing athletic performance, slowing senescence, blunting painful memories, brightening mood, and altering basic temperaments."
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    Building better polymerases: Engineering the replication of expanded genetic alphabets
    (Elsevier, 2020-12-11) Ouaray, Zahra; Benner, Steven A.; Georgiadis, Millie M.; Richards, Nigel G. J.; Biochemistry and Molecular Biology, School of Medicine
    DNA polymerases are today used throughout scientific research, biotechnology, and medicine, in part for their ability to interact with unnatural forms of DNA created by synthetic biologists. Here especially, natural DNA polymerases often do not have the "performance specifications" needed for transformative technologies. This creates a need for science-guided rational (or semi-rational) engineering to identify variants that replicate unnatural base pairs (UBPs), unnatural backbones, tags, or other evolutionarily novel features of unnatural DNA. In this review, we provide a brief overview of the chemistry and properties of replicative DNA polymerases and their evolved variants, focusing on the Klenow fragment of Taq DNA polymerase (Klentaq). We describe comparative structural, enzymatic, and molecular dynamics studies of WT and Klentaq variants, complexed with natural or noncanonical substrates. Combining these methods provides insight into how specific amino acid substitutions distant from the active site in a Klentaq DNA polymerase variant (ZP Klentaq) contribute to its ability to replicate UBPs with improved efficiency compared with Klentaq. This approach can therefore serve to guide any future rational engineering of replicative DNA polymerases.
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    Characterization of a novel RNAi yeast insecticide that silences mosquito 5-HT1 receptor genes
    (Springer Nature, 2023-12-15) Mysore, Keshava; Njoroge, Teresia M.; Stewart, Akilah T. M.; Winter, Nikhella; Hamid‑Adiamoh, Majidah; Sun, Longhua; Shui Feng, Rachel; James, Lester D.; Mohammed, Azad; Severson, David W.; Duman‑Scheel, Molly; Medical and Molecular Genetics, School of Medicine
    G protein-coupled receptors (GPCRs), which regulate numerous intracellular signaling cascades that mediate many essential physiological processes, are attractive yet underexploited insecticide targets. RNA interference (RNAi) technology could facilitate the custom design of environmentally safe pesticides that target GPCRs in select target pests yet are not toxic to non-target species. This study investigates the hypothesis that an RNAi yeast insecticide designed to silence mosquito serotonin receptor 1 (5-HTR1) genes can kill mosquitoes without harming non-target arthropods. 5-HTR.426, a Saccharomyces cerevisiae strain that expresses an shRNA targeting a site specifically conserved in mosquito 5-HTR1 genes, was generated. The yeast can be heat-inactivated and delivered to mosquito larvae as ready-to-use tablets or to adult mosquitoes using attractive targeted sugar baits (ATSBs). The results of laboratory and outdoor semi-field trials demonstrated that consumption of 5-HTR.426 yeast results in highly significant mortality rates in Aedes, Anopheles, and Culex mosquito larvae and adults. Yeast consumption resulted in significant 5-HTR1 silencing and severe neural defects in the mosquito brain but was not found to be toxic to non-target arthropods. These results indicate that RNAi insecticide technology can facilitate selective targeting of GPCRs in intended pests without impacting GPCR activity in non-targeted organisms. In future studies, scaled production of yeast expressing the 5-HTR.426 RNAi insecticide could facilitate field trials to further evaluate this promising new mosquito control intervention.
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    Chemical modification of AAV9 capsid with N-ethyl maleimide alters vector tissue tropism
    (Springer Nature, 2023-05-25) Mulcrone, Patrick L.; Lam, Anh K.; Frabutt, Dylan; Zhang, Junping; Chrzanowski, Matthew; Herzog, Roland W.; Xiao, Weidon; Pediatrics, School of Medicine
    Although more adeno-associated virus AAV-based drugs enter the clinic, vector tissue tropism remains an unresolved challenge that limits its full potential despite that the tissue tropism of naturally occurring AAV serotypes can be altered by genetic engineering capsid vie DNA shuffling, or molecular evolution. To further expand the tropism and thus potential applications of AAV vectors, we utilized an alternative approach that employs chemical modifications to covalently link small molecules to reactive exposed Lysine residues of AAV capsids. We demonstrated that AAV9 capsid modified with N-ethyl Maleimide (NEM) increased its tropism more towards murine bone marrow (osteoblast lineage) while decreased transduction of liver tissue compared to the unmodified capsid. In the bone marrow, AAV9-NEM transduced Cd31, Cd34, and Cd90 expressing cells at a higher percentage than unmodified AAV9. Moreover, AAV9-NEM localized strongly in vivo to cells lining the calcified trabecular bone and transduced primary murine osteoblasts in culture, while WT AAV9 transduced undifferentiated bone marrow stromal cells as well as osteoblasts. Our approach could provide a promising platform for expanding clinical AAV development to treat bone pathologies such as cancer and osteoporosis. Thus, chemical engineering the AAV capsid holds great potential for development of future generations of AAV vectors.
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    Different applications for genetically modified crops
    (2005-06-29) United States. Congress. House. Committee on Small Business. Subcommittee on Rural Enterprises, Agriculture, and Technology
    Congressional hearing on the various uses of biotechnology, with testimonies and prepared statements from producers in the pharmaceutical, forestry, cotton, and papaya industries.
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    An economic model of a genetic resistance commons: Effects of market structure applied to biotechnology in agriculture
    (Resources for the Future, 2003) Noonan, Douglas S.
    Genetic resistance resources represent an emerging class of environmental resources. These resources are the subject of increasing public interest, especially for resistance in agriculture and antibiotic use. This paper models genetic resistance resources as common-pool resources. The static model applies directly to the case of Bt corn, whose seeds are bioengineered to contain a pesticide. Firms produce an agricultural output, corn, using two inputs: Bt corn seeds and refuge areas. Production also depends on the common stock of environmental resistance. Seed use contributes to greater resistance, while refuge areas abate resistance. This costly form of abatement represents another (positive) externality, which allows for the optimal seed use to be greater than the competitive level. The use of seeds and refuge areas by other firms can be shown to be substitutes and compliments in production, respectively, for each firm. This simple model of externalities is complicated by introducing another important feature common to genetic resistance resources: monopoly supply in the biotechnology factor market. Monopoly provision of seeds, with imperfect price discrimination, leads the monopoly to act as a gatekeeper of the commons who tries to maximize its own rents rather than the rents from the resource. This divergence in interests leads to a deadweight loss as seed use is curtailed through higher monopoly prices. This equilibrium is compared to the competitive and the optimal cases. The way in which the resistance externality operates, through damaging others’ output or through affecting their marginal productivities, suggests whether the monopoly improves the efficiency of the seed market. Further consideration is given to the possibility that the monopoly determines the firms’ level of abatement. Assuming some enforcement mechanism, the monopoly chooses higher abatement levels to increase factor demand for seeds and increase its rents. The Under some plausible conditions, a monopoly supplier of the input that accesses the genetic resistance commons can be shown to actually improve welfare by mandating a higher level of care that also maximizes its profits. The distributional consequences of the different market structures are shown, noting how gains for the monopoly come at the expense of firms. In 2000, the EPA and Monsanto required purchasers of Bt corn to plant specific refuge areas in order to forestall resistance. This approach is readily extended to other cases, such as pesticides more generally or antibiotic use in the production of health services by households.
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    Effects of donor-specific microvascular anatomy on hemodynamic perfusion in human choriocapillaris
    (Springer Nature, 2023-12-19) An, Senyou; Yu, Huidan; Islam, MD Mahfuzul; Zhang, Xiaoyu; Zhan, Yuting; Olivieri, Joseph J.; Ambati, Jayakrishna; Yao, Jun; Gelfand, Bradley D.; Mechanical and Energy Engineering, Purdue School of Engineering and Technology
    Evidence from histopathology and clinical imaging suggest that choroidal anatomy and hemodynamic perfusion are among the earliest changes in retinal diseases such as age-related macular degeneration (AMD). However, how inner choroidal anatomy affects hemodynamic perfusion is not well understood. Therefore, we sought to understand the influences of choroidal microvascular architecture on the spatial distribution of hemodynamic parameters in choriocapillaris from human donor eyes using image-based computational hemodynamic (ICH) simulations. We subjected image-based inner choroid reconstructions from eight human donor eyes to ICH simulation using a kinetic-based volumetric lattice Boltzmann method to compute hemodynamic distributions of velocity, pressure, and endothelial shear stress. Here, we demonstrate that anatomic parameters, including arteriolar and venular arrangements and intercapillary pillar density and distribution exert profound influences on inner choroidal hemodynamic characteristics. Reductions in capillary, arteriolar, and venular density not only reduce the overall blood velocity within choriocapillaris, but also substantially increase its spatial heterogeneity. These first-ever findings improve understanding of how choroidal anatomy affects hemodynamics and may contribute to pathogenesis of retinal diseases such as AMD.
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    EU policy on biotechnology
    (Office for Official Publications of the European Communities, 2006) European Commission. Environment Directorate-General
    Describes the European Union policies and regulations regarding genetically-modified organisms (GMOs).
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    Evaluation of the IrisPlex DNA-based eye color prediction tool in the United States
    (2014-07-31) Dembinski, Gina M.; Picard, Christine; Randall, Stephen Karl, 1953-; Goodpaster, John V. (John Vincent)
    DNA phenotyping is a rapidly developing area of research in forensic biology. Externally visible characteristics (EVCs) can be determined based on genotype data, specifically from single nucleotide polymorphisms (SNPs). These SNPs are chosen based on their association with genes related to the phenotypic expression of interest, with known examples in eye, hair, and skin color traits. DNA phenotyping has forensic importance when unknown biological samples at a crime scene do not result in a criminal database hit; a phenotype profile of the sample can therefore be used to develop investigational leads. IrisPlex, an eye color prediction assay, has previously shown high prediction rates for blue and brown eye color in a European population. The objective of this work was to evaluate its utility in a North American population. We evaluated the six SNPs included in the IrisPlex assay in an admixed population sample collected from a U.S.A. college campus. We used a quantitative method of eye color classification based on (RGB) color components of digital photographs of the eye taken from each study volunteer and placed in one of three eye color categories: brown, intermediate, and blue. Objective color classification was shown to correlate with basic human visual determination making it a feasible option for use in future prediction assay development. In the original IrisPlex study with the Dutch samples, they correct prediction rates achieved were 91.6% for blue eye color and 87.5% for brown eye color. No intermediate eyes were tested. Using these samples and various models, the maximum prediction accuracies of the IrisPlex system achieved was 93% and 33% correct brown and blue eye color predictions, respectively, and 11% for intermediate eye colors. The differences in prediction accuracies is attributed to the genetic differences in allele frequencies within the sample populations tested. Future developments should include incorporation of additional informative SNPs, specifically related to the intermediate eye color, and we recommend the use of a Bayesian approach as a prediction model as likelihood ratios can be determined for reporting purposes.
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    Field trials reveal the complexities of deploying and evaluating the impacts of yeast-baited ovitraps on Aedes mosquito densities in Trinidad, West Indie
    (Springer Nature, 2022-03-08) James, Lester D.; Winter, Nikhella; Stewart, Akilah T. M.; Feng, Rachel Shui; Nandram, Naresh; Mohammed, Azad; Duman‑Scheel, Molly; Romero‑Severson, Ethan; Severson, David W.; Medical and Molecular Genetics, School of Medicine
    The use of lure-and-kill, large-volume ovitraps to control Aedes aegypti and Aedes albopictus populations has shown promise across multiple designs that target gravid females (adulticidal) or larvae post-oviposition (larvicidal). Here we report on a pilot trial to deploy 10 L yeast-baited ovitraps at select sites in Curepe, Trinidad, West Indies during July to December, 2019. Oviposition rates among ovitraps placed in three Treatment sites were compared to a limited number of traps placed in three Control areas (no Aedes management performed), and three Vector areas (subjected to standard Ministry of Health, Insect Vector Control efforts). Our goal was to gain baseline information on efforts to saturate the Treatment sites with ovitraps within 20-25 m of each other and compare oviposition rates at these sites with background oviposition rates in Control and Vector Areas. Although yeast-baited ovitraps were highly attractive to gravid Aedes females, a primary limitation encountered within the Treatment sites was the inability to gain access to residential compounds for trap placement, primarily due to residents being absent during the day. This severely limited our intent to saturate these areas with ovitraps, indicating that future studies must include plans to account for these inaccessible zones during trap placement.