27 research outputs found

    Analysis of a human brain transcriptome map

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    BACKGROUND: Genome wide transcriptome maps can provide tools to identify candidate genes that are over-expressed or silenced in certain disease tissue and increase our understanding of the structure and organization of the genome. Expressed Sequence Tags (ESTs) from the public dbEST and proprietary Incyte LifeSeq databases were used to derive a transcript map in conjunction with the working draft assembly of the human genome sequence. RESULTS: Examination of ESTs derived from brain tissues (excluding brain tumor tissues) suggests that these genes are distributed on chromosomes in a non-random fashion. Some regions on the genome are dense with brain-enriched genes while some regions lack brain-enriched genes, suggesting a significant correlation between distribution of genes along the chromosome and tissue type. ESTs from brain tumor tissues have also been mapped to the human genome working draft. We reveal that some regions enriched in brain genes show a significant decrease in gene expression in brain tumors, and, conversely that some regions lacking in brain genes show an increased level of gene expression in brain tumors. CONCLUSIONS: This report demonstrates a novel approach for tissue specific transcriptome mapping using EST-based quantitative assessment

    Developing Novel Molecular Targeted Therapeutics for Topical Treatment of Psoriasis

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    Psoriasis is a chronic inflammatory skin disorder. The prevalence of psoriasis is estimated at approximately 100 million people worldwide. In mild-to-moderate, as well as moderate-to-severe, psoriasis, 70ā€“80% of patients start with topical agents and continue to use them with other active therapies. This group of patients can benefit from topical treatment with minimal systemic exposure. The expression levels of IL-23 and IL-17 are upregulated in psoriatic skin compared with non-lesional skin, associated with psoriasis pathogenesis. The skin epidermal proliferation and psoriasis are caused by overactive Th17 cells, which are promoted and stabilized by the activated IL-23 receptor, forming part of the positive feedback loop. FDA approved biologics in IL-23/IL-17 axis (ustekinumab, guselkumab, risankizumab, tildrakizumab, ixekizumab, secukinumab and brodalumab) demonstrated superior clinical efficacy in the systemic treatment of moderate-to-severe psoriasis, providing the clinical proof of concept of the IL-23/IL-17 axis as a major immune pathway underlying the pathophysiology of psoriasis. However, due to the large size and poor permeability into skin, biologics are not suitable to deliver via topical route. Current topical treatments of mild-to-moderate psoriasis are corticosteroids and vitamin D analogues, which have limited efficacy with significant side effects so that patients must avoid long-term use. This chapter reviews current molecular targeted therapeutics under development for topical treatment of psoriasis

    A reference database for tumor-related genes co-expressed with interleukin-8 using genome-scale in silico analysis

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    BACKGROUND: The EST database provides a rich resource for gene discovery and in silico expression analysis. We report a novel computational approach to identify co-expressed genes using EST database, and its application to IL-8. RESULTS: IL-8 is represented in 53 dbEST cDNA libraries. We calculated the frequency of occurrence of all the genes represented in these cDNA libraries, and ranked the candidates based on a Z-score. Additional analysis suggests that most IL-8 related genes are differentially expressed between non-tumor and tumor tissues. To focus on IL-8's function in tumor tissues, we further analyzed and ranked the genes in 16 IL-8 related tumor libraries. CONCLUSIONS: This method generated a reference database for genes co-expressed with IL-8 and could facilitate further characterization of functional association among genes

    PlantCV v2: Image analysis software for high-throughput plant phenotyping

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    Systems for collecting image data in conjunction with computer vision techniques are a powerful tool for increasing the temporal resolution at which plant phenotypes can be measured non-destructively. Computational tools that are flexible and extendable are needed to address the diversity of plant phenotyping problems. We previously described the Plant Computer Vision (PlantCV) software package, which is an image processing toolkit for plant phenotyping analysis. The goal of the PlantCV project is to develop a set of modular, reusable, and repurposable tools for plant image analysis that are open-source and community-developed. Here we present the details and rationale for major developments in the second major release of PlantCV. In addition to overall improvements in the organization of the PlantCV project, new functionality includes a set of new image processing and normalization tools, support for analyzing images that include multiple plants, leaf segmentation, landmark identification tools for morphometrics, and modules for machine learning

    Comparison of openā€source threeā€dimensional reconstruction pipelines for maizeā€root phenotyping

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    Abstract Understanding threeā€dimensional (3D) root traits is essential to improve water uptake, increase nitrogen capture, and raise carbon sequestration from the atmosphere. However, quantifying 3D root traits by reconstructing 3D root models for deeper fieldā€grown roots remains a challenge due to the unknown tradeoff between 3D rootā€model quality and 3D rootā€trait accuracy. Therefore, we performed two computational experiments. We first compared the 3D model quality generated by five stateā€ofā€theā€art openā€source 3D model reconstruction pipelines on 12 contrasting genotypes of fieldā€grown maize roots. These pipelines included COLMAP, COLMAP+PMVS (Patchā€based Multiā€View Stereo), VisualSFM, Meshroom, and OpenMVG+MVE (Multiā€View Environment). The COLMAP pipeline achieved the best performance regarding 3D model quality versus computational time and image number needed. In the second test, we compared the accuracy of 3D rootā€trait measurement generated by the Digital Imaging of Root Traits 3D pipeline (DIRT/3D) using COLMAPā€based 3D reconstruction with our current DIRT/3D pipeline that uses a VisualSFMā€based 3D reconstruction on the same dataset of 12 genotypes, with 5ā€“10 replicates per genotype. The results revealed that (1) the average number of images needed to build a denser 3D model was reduced from 3000 to 3600 (DIRT/3D [VisualSFMā€based 3D reconstruction]) to around 360 for computational test 1, and around 600 for computational test 2 (DIRT/3D [COLMAPā€based 3D reconstruction]); (2) denser 3D models helped improve the accuracy of the 3D rootā€trait measurement; (3) reducing the number of images can help resolve data storage problems. The updated DIRT/3D (COLMAPā€based 3D reconstruction) pipeline enables quicker image collection without compromising the accuracy of 3D rootā€trait measurements

    Comparison of openā€source threeā€dimensional reconstruction pipelines for maizeā€root phenotyping

    No full text
    Understanding three-dimensional (3D) root traits is essential to improve water uptake, increase nitrogen capture, and raise carbon sequestration from the atmosphere. However, quantifying 3D root traits by reconstructing 3D root models for deeper field-grown roots remains a challenge due to the unknown tradeoff between 3D root-model quality and 3D root-trait accuracy. Therefore, we performed two computational experiments. We first compared the 3D model quality generated by five state-of-the-art open-source 3D model reconstruction pipelines on 12 contrasting genotypes of field-grown maize roots. These pipelines included COLMAP, COLMAP+PMVS (Patch-based Multi-View Stereo), VisualSFM, Meshroom, and OpenMVG+MVE (Multi-View Environment). The COLMAP pipeline achieved the best performance regarding 3D model quality versus computational time and image number needed. In the second test, we compared the accuracy of 3D root-trait measurement generated by the Digital Imaging of Root Traits 3D pipeline (DIRT/3D) using COLMAP-based 3D reconstruction with our current DIRT/3D pipeline that uses a VisualSFM-based 3D reconstruction on the same dataset of 12 genotypes, with 5ā€“10 replicates per genotype. The results revealed that (1) the average number of images needed to build a denser 3D model was reduced from 3000 to 3600 (DIRT/3D [VisualSFM-based 3D reconstruction]) to around 360 for computational test 1, and around 600 for computational test 2 (DIRT/3D [COLMAP-based 3D reconstruction]); (2) denser 3D models helped improve the accuracy of the 3D root-trait measurement; (3) reducing the number of images can help resolve data storage problems. The updated DIRT/3D (COLMAP-based 3D reconstruction) pipeline enables quicker image collection without compromising the accuracy of 3D root-trait measurements.National Science FoundationOpen access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

    Novel Low Cost 3D Surface Model Reconstruction System for Plant Phenotyping

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    Accurate high-resolution three-dimensional (3D) models are essential for a non-invasive analysis of phenotypic characteristics of plants. Previous limitations in 3D computer vision algorithms have led to a reliance on volumetric methods or expensive hardware to record plant structure. We present an image-based 3D plant reconstruction system that can be achieved by using a single camera and a rotation stand. Our method is based on the structure from motion method, with a SIFT image feature descriptor. In order to improve the quality of the 3D models, we segmented the plant objects based on the PlantCV platform. We also deducted the optimal number of images needed for reconstructing a high-quality model. Experiments showed that an accurate 3D model of the plant was successfully could be reconstructed by our approach. This 3D surface model reconstruction system provides a simple and accurate computational platform for non-destructive, plant phenotyping

    Modular mutagenesis of exons 1, 2, and 8 of a glutathione S-transferase from the Mu class. Mechanistic and structural consequences for chimeras of isoenzyme 3-3

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    Exons 1 and 2 and exon 8 of the mu class GSH transferases from rat encode sequence-variable regions 1 and 4 of mu class isoenzymes, respectively. These two of four variable regions are located at the N- and C-termini of this isoenzyme class and impinge on the active site. In order to assess the influence of these variable regions on the catalytic diversity of the class mu isoenzymes, seven chimeric isoenzymes were constructed by transplantation of the variable regions of the sequence of the type 4 subunit into the corresponding regions of the type 3 subunit. The chimeric isoenzymes exhibit unique catalytic properties. Replacement of all, or part, of variable region 4 of the type 3 subunit with that of the type 4 subunit results in chimeric catalysts with higher turnover numbers in nucleophilic aromatic substitution reactions. Analysis of the crystal structure of isoenzyme 3-3 [Ji, X., Zhang, P., Armstrong, R. N., & Gilliland, G. L. (1992) Biochemistry (preceding paper in this issue)] suggests that interaction of the flexible C-terminal tail with the N-terminal domain helps limit the rate of product release from the active site of isoenzyme 3-3 in this type of reaction. Substitution of all, or part, of the sequence-variable region 1 of subunit 3 with that of subunit 4 results in chimeric isoenzymes that mimic the high stereoselectivity but not the catalytic efficiency of isoenzyme 4-4 toward a,/3-unsaturated ketones. Modular mutagenesis of the N-terminal variable region together with linear free energy relationships using para-substituted 4-phenyl-3-buten-2-ones and the crystal structure of isoenzyme 3-3 has allowed the rapid location of a mutation, V9I, which appears to be crucial in determining the stereoselectivity of the chimeras and, by implication, isoenzyme 4-4 toward phenylbutenones and arene oxides

    Modular mutagenesis of exons 1, 2, and 8 of a glutathione S-transferase from the Mu class. Mechanistic and structural consequences for chimeras of isoenzyme 3-3

    No full text
    Exons 1 and 2 and exon 8 of the mu class GSH transferases from rat encode sequence-variable regions 1 and 4 of mu class isoenzymes, respectively. These two of four variable regions are located at the N- and C-termini of this isoenzyme class and impinge on the active site. In order to assess the influence of these variable regions on the catalytic diversity of the class mu isoenzymes, seven chimeric isoenzymes were constructed by transplantation of the variable regions of the sequence of the type 4 subunit into the corresponding regions of the type 3 subunit. The chimeric isoenzymes exhibit unique catalytic properties. Replacement of all, or part, of variable region 4 of the type 3 subunit with that of the type 4 subunit results in chimeric catalysts with higher turnover numbers in nucleophilic aromatic substitution reactions. Analysis of the crystal structure of isoenzyme 3-3 [Ji, X., Zhang, P., Armstrong, R. N., & Gilliland, G. L. (1992) Biochemistry (preceding paper in this issue)] suggests that interaction of the flexible C-terminal tail with the N-terminal domain helps limit the rate of product release from the active site of isoenzyme 3-3 in this type of reaction. Substitution of all, or part, of the sequence-variable region 1 of subunit 3 with that of subunit 4 results in chimeric isoenzymes that mimic the high stereoselectivity but not the catalytic efficiency of isoenzyme 4-4 toward a,/3-unsaturated ketones. Modular mutagenesis of the N-terminal variable region together with linear free energy relationships using para-substituted 4-phenyl-3-buten-2-ones and the crystal structure of isoenzyme 3-3 has allowed the rapid location of a mutation, V9I, which appears to be crucial in determining the stereoselectivity of the chimeras and, by implication, isoenzyme 4-4 toward phenylbutenones and arene oxides
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