Browsing by Subject "Development"

Now showing 1 - 10 of 68
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    Access to Knowledge in Brazil: New Research on Intellectual Property, Innovation and Development
    (Bloomsbury Academic, 2010) Shaver, Lea
    Access to knowledge is a demand for democratic participation, for global inclusion and for economic justice. It is a reaction to the excessively restrictive international IP regime put in place over the last two decades, which seeks to reassert the public interest in a more balanced information policy. With sponsorship from the Ford Foundation, the Information Society Project at Yale Law School has embarked on a new series of access to knowledge research, in partnership with colleagues in Brazil, China, Egypt, Ethiopia, India, Russia and South Africa. The first book in this series, Access to Knowledge in Brazil, focuses on current issues in intellectual property, innovation and development policy from a Brazilian perspective. Each chapter is authored by scholars from the Fundação Getulio Vargas law schools in São Paolo and Rio de Janeiro and examines a policy area that significantly impacts access to knowledge in the country. These include: exceptions and limitations to copyright, free software and open business models, patent reform and access to medicines, and open innovation in the biotechnology sector.
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    Access to Knowledge in Egypt: New Research on Intellectual Property, Innovation and Development
    (Bloomsbury Academic, 2010) Shaver, Lea; Rizk, Nagla
    The conventional wisdom in Egypt examines the issue of intellectual property solely as a question of policing and enforcement. The high levels of protection indicated by the WTO Agreement on Trade Related Aspects of Intellectual Property Rights are unquestioningly assumed to be desirable. Policy debates - and all too often academic ones as well - focus only on the questions of how to more efficiently tighten IP protection and crack down on piracy. Yet a more critical examination is urgently needed, whereby IP law, policy, and practice are viewed from a development perspective, rather than from an enforcement perspective. This volume takes on this endeavor. It offers the first examination of IP issues in Egypt adopting a multidisciplinary bottom-up approach that aims at maximizing access and contribution to knowledge, and in turn, promoting development. Bringing rigorous empirical research to bear on unquestioned ideologies, the collaborating authors question the conventional wisdom that more IP protection is necessarily better for innovation and development.
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    Advances in pediatric acute kidney injury pharmacology and nutrition: a report from the 26th Acute Disease Quality Initiative (ADQI) consensus conference
    (Springer, 2024) Wong Vega, Molly; Starr, Michelle C.; Brophy, Patrick D.; Devarajan, Prasad; Soranno, Danielle E.; Akcan‑Arikan, Ayse; Basu, Rajit; Goldstein, Stuart L.; Charlton, Jennifer R.; Barreto, Erin; Pediatrics, School of Medicine
    Background: In the past decade, there have been substantial advances in our understanding of pediatric AKI. Despite this progress, large gaps remain in our understanding of pharmacology and nutritional therapy in pediatric AKI. Methods: During the 26th Acute Disease Quality Initiative (ADQI) Consensus Conference, a multidisciplinary group of experts reviewed the evidence and used a modified Delphi process to achieve consensus on recommendations for gaps and advances in care for pharmacologic and nutritional management of pediatric AKI. The current evidence as well as gaps and opportunities were discussed, and recommendations were summarized. Results: Two consensus statements were developed. (1) High-value, kidney-eliminated medications should be selected for a detailed characterization of their pharmacokinetics, pharmacodynamics, and pharmaco-"omics" in sick children across the developmental continuum. This will allow for the optimization of real-time modeling with the goal of improving patient care. Nephrotoxin stewardship will be identified as an organizational priority and supported with necessary resources and infrastructure. (2) Patient-centered outcomes (functional status, quality of life, and optimal growth and development) must drive targeted nutritional interventions to optimize short- and long-term nutrition. Measures of acute and chronic changes of anthropometrics, body composition, physical function, and metabolic control should be incorporated into nutritional assessments. Conclusions: Neonates and children have unique metabolic and growth parameters compared to adult patients. Strategic investments in multidisciplinary translational research efforts are required to fill the knowledge gaps in nutritional requirements and pharmacological best practices for children with or at risk for AKI.
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    Age-Related Changes in MicroRNA Expression and Pharmacogenes in Human Liver
    (Wiley, 2015-08) Burgess, Kimberly S.; Philips, Santosh; Benson, Eric A.; Desta, Zeruesenay; Gaedigk, Andrea; Gaedigk, Roger; Segar, Matthew W.; Liu, Yunlong; Skaar, Todd C.; Department of Pharmacology and Toxicology, IU School of Medicine
    Developmental changes in the liver can significantly impact drug disposition. Due to the emergence of microRNAs (miRNAs) as important regulators of drug disposition gene expression, we studied age-dependent changes in miRNA expression. Expression of 533 miRNAs was measured in 90 human liver tissues (fetal, pediatric [1-17 years], and adult [28-80 years]; n = 30 each). In all, 114 miRNAs were upregulated and 72 were downregulated from fetal to pediatric, and 2 and 3, respectively, from pediatric to adult. Among the developmentally changing miRNAs, 99 miRNA-mRNA interactions were predicted or experimentally validated (e.g., hsa-miR-125b-5p-CYP1A1; hsa-miR-34a-5p-HNF4A). In human liver samples (n = 10 each), analyzed by RNA-sequencing, significant negative correlations were observed between the expression of >1,000 miRNAs and mRNAs of drug disposition and regulatory genes. Our data suggest a mechanism for the marked changes in hepatic gene expression between the fetal and pediatric developmental periods, and support a role for these age-dependent miRNAs in regulating drug disposition.
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    Astrocytes Regulate the Development and Maturation of Retinal Ganglion Cells Derived from Human Pluripotent Stem Cells
    (Elsevier, 2019-02-12) VanderWall, Kirstin B.; Vij, Ridhima; Ohlemacher, Sarah K.; Sridhar, Akshayalakshmi; Fligor, Clarisse M.; Feder, Elyse M.; Edler, Michael C.; Baucum, Anthony J.; Cummins, Theodore R.; Meyer, Jason S.; Biology, School of Science
    Retinal ganglion cells (RGCs) form the connection between the eye and the brain, with this connectivity disrupted in numerous blinding disorders. Previous studies have demonstrated the ability to derive RGCs from human pluripotent stem cells (hPSCs); however, these cells exhibited some characteristics that indicated a limited state of maturation. Among the many factors known to influence RGC development in the retina, astrocytes are known to play a significant role in their functional maturation. Thus, efforts of the current study examined the functional maturation of hPSC-derived RGCs, including the ability of astrocytes to modulate this developmental timeline. Morphological and functional properties of RGCs were found to increase over time, with astrocytes significantly accelerating the functional maturation of hPSC-derived RGCs. The results of this study clearly demonstrate the functional and morphological maturation of RGCs in vitro, including the effects of astrocytes on the maturation of hPSC-derived RGCs.
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    Build your own retina: modeling retinogenesis and disease using human pluripotent stem cells
    (2017) Sridhar, Akshayalakshmi; Meyer, Jason
    Human pluripotent stem cells (hPSCs) allow for the unprecedented ability to recapitulate early stages of human development, which are otherwise inaccessible to investigation. This is especially true for one of the earliest events in human development, the establishment of a neuroretinal fate from an unspecified pluripotent population. To test the ability of hPSCs to serve in this capacity, hPSCs were generated using mRNA-reprogamming methods and maintained in xenogeneic-free differentiation conditions. These cells were directed to differentiate using a three-dimensional approach to analyze their ability to successfully recapitulate early events in human development in a temporal and developmentally-appropriate fashion. To do so, hPSCs were first directed to an anterior neural phenotype, which was confirmed by analysis of stage-specific neural transcription factors via immunocytochemistry and quantitative RT-PCR. Next, the cells were directed to an optic vesicle-like stage, where the presumptive retinal cells were identified by the expression of specific transcription factors. Finally, three-dimensional optic vesicle-like retinal organoids were identified, isolated, and further analyzed for the expression of markers associated with some of the differentiated cell types of the neural retina. Upon establishment of hPSC-derived retinal organoids, this system was further utilized to study the neurodegeneration in glaucoma and provide insights into the disease mechanisms. Overall, the results of this study help to demonstrate the suitability of hPSC-differentiation approaches as an effective tool to model retinal development and disease.
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    Cell-Cell Communication Breakdown and Endothelial Dysfunction
    (Elsevier, 2020-04) Lee, Daniel D.; Schwarz, Margaret A.; Medicine, School of Medicine
    Guided by organ-specific signals in both development and disease response, the heterogeneous endothelial cell population is a dynamic member of the vasculature. Functioning as the gatekeeper to fluid, inflammatory cells, oxygen, and nutrients, endothelial cell communication with its local environment is critical. Impairment of endothelial cell-cell communication not only disrupts this signaling process, but also contributes to pathologic disease progression. Expanding our understanding of those processes that mediate endothelial cell-cell communication is an important step in the approach to treatment of disease processes.
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    Cerebellar Structure and Function in Autism Spectrum Disorder
    (Hapres, 2022) Bloomer, Bess F.; Morales, Jaime J.; Bolbecker, Amanda R.; Kim, Dae-Jin; Hetrick, William P.; Psychiatry, School of Medicine
    Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition characterized by early-onset repetitive behaviors, restricted interests, sensory and motor difficulties, and impaired social interactions. Converging evidence from neuroimaging, lesion and postmortem studies, and rodent models suggests cerebellar involvement in ASD and points to promising targets for therapeutic interventions for the disorder. This review elucidates understanding of cerebellar mechanisms in ASD by integrating and contextualizing recent structural and functional cerebellar research.
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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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    Chitosan/interfering RNA nanoparticle mediated gene silencing in disease vector mosquito larvae
    (JOVE, 2015-03-25) Zhang, Xin; Mysore, Keshava; Flannery, Ellen; Michel, Kristin; Severson, David W.; Zhu, Kun Yan; Duman-Scheel, Molly; Department of Medical and Molecular Genetics, IU School of Medicine
    Vector mosquitoes inflict more human suffering than any other organism-and kill more than one million people each year. The mosquito genome projects facilitated research in new facets of mosquito biology, including functional genetic studies in the primary African malaria vector Anopheles gambiae and the dengue and yellow fever vector Aedes aegypti. RNA interference- (RNAi-) mediated gene silencing has been used to target genes of interest in both of these disease vector mosquito species. Here, we describe a procedure for preparation of chitosan/interfering RNA nanoparticles that are combined with food and ingested by larvae. This technically straightforward, high-throughput, and relatively inexpensive methodology, which is compatible with long double stranded RNA (dsRNA) or small interfering RNA (siRNA) molecules, has been used for the successful knockdown of a number of different genes in A. gambiae and A. aegypti larvae. Following larval feedings, knockdown, which is verified through qRT-PCR or in situ hybridization, can persist at least through the late pupal stage. This methodology may be applicable to a wide variety of mosquito and other insect species, including agricultural pests, as well as other non-model organisms. In addition to its utility in the research laboratory, in the future, chitosan, an inexpensive, non-toxic and biodegradable polymer, could potentially be utilized in the field.