38 research outputs found
Development and bin mapping of gene-associated interspecific SNPs for cotton (Gossypium hirsutum L.) introgression breeding efforts
BACKGROUND: Cotton (Gossypium spp.) is the largest producer of natural fibers for textile and is an important crop worldwide. Crop production is comprised primarily of G. hirsutum L., an allotetraploid. However, elite cultivars express very small amounts of variation due to the species monophyletic origin, domestication and further bottlenecks due to selection. Conversely, wild cotton species harbor extensive genetic diversity of prospective utility to improve many beneficial agronomic traits, fiber characteristics, and resistance to disease and drought. Introgression of traits from wild species can provide a natural way to incorporate advantageous traits through breeding to generate higher-producing cotton cultivars and more sustainable production systems. Interspecific introgression efforts by conventional methods are very time-consuming and costly, but can be expedited using marker-assisted selection. RESULTS: Using transcriptome sequencing we have developed the first gene-associated single nucleotide polymorphism (SNP) markers for wild cotton species G. tomentosum, G. mustelinum, G. armourianum and G. longicalyx. Markers were also developed for a secondary cultivated species G. barbadense cv. 3â79. A total of 62,832 non-redundant SNP markers were developed from the five wild species which can be utilized for interspecific germplasm introgression into cultivated G. hirsutum and are directly associated with genes. Over 500 of the G. barbadense markers have been validated by whole-genome radiation hybrid mapping. Overall 1,060 SNPs from the five different species have been screened and shown to produce acceptable genotyping assays. CONCLUSIONS: This large set of 62,832 SNPs relative to cultivated G. hirsutum will allow for the first high-density mapping of genes from five wild species that affect traits of interest, including beneficial agronomic and fiber characteristics. Upon mapping, the markers can be utilized for marker-assisted introgression of new germplasm into cultivated cotton and in subsequent breeding of agronomically adapted types, including cultivar development. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2164-15-945) contains supplementary material, which is available to authorized users
Niche-Based Screening in Multiple Myeloma Identifies a Kinesin-5 Inhibitor with Improved Selectivity over Hematopoietic Progenitors
SummaryNovel therapeutic approaches are urgently required for multiple myeloma (MM). We used a phenotypic screening approach using co-cultures of MM cells with bone marrow stromal cells to identify compounds that overcome stromal resistance. One such compound, BRD9876, displayed selectivity over normal hematopoietic progenitors and was discovered to be an unusual ATP non-competitive kinesin-5 (Eg5) inhibitor. A novel mutation caused resistance, suggesting a binding site distinct from known Eg5 inhibitors, and BRD9876 inhibited only microtubule-bound Eg5. Eg5 phosphorylation, which increases microtubule binding, uniquely enhanced BRD9876 activity. MM cells have greater phosphorylated Eg5 than hematopoietic cells, consistent with increased vulnerability specifically to BRD9876âs mode of action. Thus, differences in Eg5-microtubule binding between malignant and normal blood cells may be exploited to treat multiple myeloma. Additional steps are required for further therapeutic development, but our results indicate that unbiased chemical biology approaches can identify therapeutic strategies unanticipated by prior knowledge of protein targets
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Niche-Based Screening in Multiple Myeloma Identifies a Kinesin-5 Inhibitor with Improved Selectivity over Hematopoietic Progenitors
Novel therapeutic approaches are urgently required for multiple myeloma (MM). We used a phenotypic screening approach using co-cultures of MM cells with bone marrow stromal cells to identify compounds that overcome stromal resistance. One such compound, BRD9876, displayed selectivity over normal hematopoietic progenitors and was discovered to be an unusual ATP non-competitive kinesin-5 (Eg5) inhibitor. A novel mutation caused resistance, suggesting a binding site distinct from known Eg5 inhibitors, and BRD9876 inhibited only microtubule-bound Eg5. Eg5 phosphorylation, which increases microtubule binding, uniquely enhanced BRD9876 activity. MM cells have greater phosphorylated Eg5 than hematopoietic cells, consistent with increased vulnerability specifically to BRD9876âs mode of action. Thus, differences in Eg5-microtubule binding between malignant and normal blood cells may be exploited to treat multiple myeloma. Additional steps are required for further therapeutic development, but our results indicate that unbiased chemical biology approaches can identify therapeutic strategies unanticipated by prior knowledge of protein targets
Creating Safe Space in a Multidisciplinary Classroom
In todayâs political environment, making our classes a safe space for everyone, while at the same time allowing for all voices to be heard, can sometimes be a challenge. This paper will examine the benefits and challenges of creating such a classroom around a course that uses place-based pedagogy, along with feminist pedagogy and community engagement. While at first these three perspectives might seem counter to one another, or take up too much space singularly to allow proper exploration of each perspective within the confines of a sixteen week course, my recent experience teaching a cross-listed course called âAppalachian Women: Activists for Change,â shows that the connections between place, gender, community, and activism are deepened when explored in an inter-disciplinary course where discussion meets action as service. I found that utilizing an intersectional approach within the Appalachian Studies classroom allows students who do not identify themselves as Appalachian, but might identify with other intersectional issues such as race, gender, and class, to see a space for themselves within the discipline. Moreover, the additional service component of the course widened studentsâ ideas about activism and assisted them in deeply connecting with the community beyond the confines of the physical classroom space
High-throughput Identification of Phage-derived Imaging Agents
The use of phage-displayed peptide libraries is a powerful method for selecting peptides with desired binding properties. However, the validation and prioritization of âhitsâ obtained from this screening approach remains challenging. Here, we describe the development and testing of a new analysis method to identify and display hits from phage-display experiments and high-throughput enzyme-linked immunosorbent assay screens. We test the method using a phage screen against activated macrophages to develop imaging agents with higher specificity for active disease processes. The new methodology should be useful in identifying phage hits and is extendable to other library screening methods such as small-molecule and nanoparticle libraries
High-throughput Identification of Phage-derived Imaging Agents
The use of phage-displayed peptide libraries is a powerful method for selecting peptides with desired binding properties. However, the validation and prioritization of âhitsâ obtained from this screening approach remains challenging. Here, we describe the development and testing of a new analysis method to identify and display hits from phage-display experiments and high-throughput enzyme-linked immunosorbent assay screens. We test the method using a phage screen against activated macrophages to develop imaging agents with higher specificity for active disease processes. The new methodology should be useful in identifying phage hits and is extendable to other library screening methods such as small-molecule and nanoparticle libraries
The Economic Diplomacy of Small States. A Case Study of the Grand Duchy of Luxembourg: Trade and Services, Official Development Assistance (ODA), Foreign Direct Investment (FDI)
In the contemporary globalised, multi-polar and competitive conditions, small states, which count for more than half of the worldâs states, through economic diplomacy endeavours aim to position themselves in the best possible way, in order to assure their economic development and political influence. Being constrained by their size, in terms of population and economy, small states follow different strategic choices in different regions of the world. With an area totalling 2,586 km2 and a population of 590,667 in 2017, the Grand Duchy of Luxembourg is one of the smallest countries in Europe, and ranked 179th in size of all the 194 independent states of the world. Despite its size the country has been advocating openness, and enjoys a successful track record in economic diplomacy. There are, however, no in-depth academic studies to take a detailed account of its parameters and to identify its strengths and weaknesses. The present work uses Luxembourg, as a case study for evaluating economic diplomacy of small states. This is the first study of the Grand Duchyâs economic diplomacy. Based on statistical data, it goes beyond a mere account, by critically evaluating Luxembourgâs economic diplomacy in terms of trade, Foreign Direct Investment (FDI) and Official Development Assistance (ODA). While in need of imports in trade and investment due to its limited production possibilities given its size and the consumption needs of its affluent society, we claim that, without shying away, the country dared to compete in the globalised markets using an efficient and effective, well developed economic diplomacy, in order to: a) export its goods and services, b) attract inward FDI, while c) sharing part of its wealth with developing countries through the provision of ODA. Based on the results of Luxembourg as a case study, we argue that size is not a determinant of a stateâs economic diplomacy success
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