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https://www.readbyqxmd.com/read/28647089/reverse-phase-protein-arrays-elucidate-mechanisms-of-action-and-phenotypic-response-in-2d-and-3d-models
#1
REVIEW
Michael Pawlak, Neil O Carragher
The development of new 2D and 3D phenotypic screening assays combined with high-throughput genomic and proteomic technologies are well placed to advance a new era of molecular pathway informed Phenotypic Drug Discovery. We describe the application of Reverse Phase Protein Array (RPPA) technology to elucidate the mechanism-of-action of small molecules at the post-translational pathway level. We propose that profiling of phenotypic hits and lead molecules in increasingly more complex 3D in vitro and ex vivo models at the post-translational pathway network level represents an effective strategy to both triage and progress the preclinical development of phenotypic screening hits...
March 2017: Drug Discovery Today. Technologies
https://www.readbyqxmd.com/read/28643930/moving-towards-precision-orthodontics-an-evolving-paradigm-shift-in-the-planning-and-delivery-of-customized-orthodontic-therapy
#2
REVIEW
A H Jheon, S Oberoi, R C Solem, S Kapila
Advances in precision medicine portend similar progress in orthodontics and will be increasingly harnessed to achieve customized treatment approaches and enhance treatment efficiencies. Our goal is to provide a background on emerging advances in computer technologies and biomedicine and highlight their current and likely future applications to precision orthodontics. A review of orthodontically relevant technologies and advances in pertinent biological research was undertaken. Innovations in computer hardware and software, and 3D imaging technologies offer the ability for customized treatment and biomechanical planning that will be more fully realized within the next few decades...
June 2017: Orthodontics & Craniofacial Research
https://www.readbyqxmd.com/read/28643915/preface-to-coast-2016-innovators-workshop-on-personalized-and-precision-orthodontic-therapy
#3
J C Nickel, D A Covell, S A Frazier-Bowers, S Kapila, S S Huja, L R Iwasaki
OBJECTIVE: A second focused workshop explored how to transfer novel findings into clinical orthodontic practice. SETTING AND SAMPLE POPULATION: Participants met in West Palm Beach (Florida, USA), on 9-11 September 2016 for the Consortium for Orthodontic Advances in Science and Technology 2016 Innovators' Workshop (COAST). Approximately 65 registered attendees considered and discussed information from 27 to 34 speakers, 8 to 15 poster presenters and four lunch-hour focus group leaders...
June 2017: Orthodontics & Craniofacial Research
https://www.readbyqxmd.com/read/28629892/engineered-myocardium-model-to-study-the-roles-of-hif-1%C3%AE-and-hif1a-as1-in-paracrine-only-signaling-under-pathological-level-oxidative-stress
#4
Aylin Acun, Pinar Zorlutuna
Studying heart tissue is critical for understanding and developing treatments for cardiovascular diseases. In this work, we fabricated precisely controlled and biomimetic engineered model tissues to study how cell-cell and cell-matrix interactions influence myocardial cell survival upon exposure to pathological level oxidative stress. Specifically, the interactions of endothelial cells (ECs) and cardiomyocytes (CMs), and the role of hypoxia inducible factor-1α (HIF-1α), with its novel alternative regulator, HIF-1α antisense RNA1 (HIF1A-AS1), in these interactions were investigated...
June 16, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28620124/a-high-throughput-field-based-phenotyping-technology-for-tall-biomass-crops
#5
Maria G Salas Fernandez, Yin Bao, Lie Tang, Patrick S Schnable
Recent advances in "omics" technologies have not been accompanied by equally efficient, cost-effective and accurate phenotyping methods required to dissect the genetic architecture of complex traits. Even though high-throughput phenotyping platforms have been developed for controlled environments, field-based aerial and ground technologies have only been designed and deployed for short stature crops. Therefore, we developed and tested Phenobot 1.0, an auto-steered and self-propelled field-based high-throughput phenotyping platform for tall dense canopy crops, such as sorghum (Sorghum bicolor L...
June 15, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28616808/crop-3d-a-lidar-based-platform-for-3d-high-throughput-crop-phenotyping
#6
Qinghua Guo, Fangfang Wu, Shuxin Pang, Xiaoqian Zhao, Linhai Chen, Jin Liu, Baolin Xue, Guangcai Xu, Le Li, Haichun Jing, Chengcai Chu
With the growing population and the reducing arable land, breeding has been considered as an effective way to solve the food crisis. As an important part in breeding, high-throughput phenotyping can accelerate the breeding process effectively. Light detection and ranging (LiDAR) is an active remote sensing technology that is capable of acquiring three-dimensional (3D) data accurately, and has a great potential in crop phenotyping. Given that crop phenotyping based on LiDAR technology is not common in China, we developed a high-throughput crop phenotyping platform, named Crop 3D, which integrated LiDAR sensor, high-resolution camera, thermal camera and hyperspectral imager...
December 6, 2017: Science China. Life Sciences
https://www.readbyqxmd.com/read/28610595/stem-cell-models-of-alzheimer-s-disease-progress-and-challenges
#7
REVIEW
Charles Arber, Christopher Lovejoy, Selina Wray
A major challenge to our understanding of the molecular mechanisms of Alzheimer's disease (AD) has been the lack of physiologically relevant in vitro models which capture the precise patient genome, in the cell type of interest, with physiological expression levels of the gene(s) of interest. Induced pluripotent stem cell (iPSC) technology, together with advances in 2D and 3D neuronal differentiation, offers a unique opportunity to overcome this challenge and generate a limitless supply of human neurons for in vitro studies...
June 13, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28605460/modmaps3d-an-interactive-webtool-for-the-quantification-and-3d-visualization-of-interrelationships-in-a-dataset-of-dna-sequences
#8
Rallis Karamichalis, Lila Kari
Summary: MoDMaps3D (Molecular Distance Maps 3D) is an alignment-free, fast, computationally lightweight webtool for computing and visualizing the interrelationships within any dataset of DNA sequences, based on pairwise comparisons between their oligomer compositions. MoDMaps3D is a general-purpose interactive webtool that is free of any requirements on sequence composition, position of the sequences in their respective genomes, presence or absence of similarity or homology, sequence length, or even sequence origin (biological or computer-generated)...
June 10, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28604723/fish-ing-for-captured-contacts-towards-reconciling-fish-and-3c
#9
Geoffrey Fudenberg, Maxim Imakaev
Chromosome conformation capture (3C) and fluorescence in situ hybridization (FISH) are two widely used technologies that provide distinct readouts of 3D chromosome organization. While both technologies can assay locus-specific organization, how to integrate views from 3C, or genome-wide Hi-C, and FISH is far from solved. Contact frequency, measured by Hi-C, and spatial distance, measured by FISH, are often assumed to quantify the same phenomena and used interchangeably. Here, however, we demonstrate that contact frequency is distinct from average spatial distance, both in polymer simulations and in experimental data...
June 12, 2017: Nature Methods
https://www.readbyqxmd.com/read/28604721/comparison-of-computational-methods-for-hi-c-data-analysis
#10
Mattia Forcato, Chiara Nicoletti, Koustav Pal, Carmen Maria Livi, Francesco Ferrari, Silvio Bicciato
Hi-C is a genome-wide sequencing technique used to investigate 3D chromatin conformation inside the nucleus. Computational methods are required to analyze Hi-C data and identify chromatin interactions and topologically associating domains (TADs) from genome-wide contact probability maps. We quantitatively compared the performance of 13 algorithms in their analyses of Hi-C data from six landmark studies and simulations. This comparison revealed differences in the performance of methods for chromatin interaction identification, but more comparable results for TAD detection between algorithms...
June 12, 2017: Nature Methods
https://www.readbyqxmd.com/read/28604675/identification-of-the-elementary-structural-units-of-the-dna-damage-response
#11
Francesco Natale, Alexander Rapp, Wei Yu, Andreas Maiser, Hartmann Harz, Annina Scholl, Stephan Grulich, Tobias Anton, David Hörl, Wei Chen, Marco Durante, Gisela Taucher-Scholz, Heinrich Leonhardt, M Cristina Cardoso
Histone H2AX phosphorylation is an early signalling event triggered by DNA double-strand breaks (DSBs). To elucidate the elementary units of phospho-H2AX-labelled chromatin, we integrate super-resolution microscopy of phospho-H2AX during DNA repair in human cells with genome-wide sequencing analyses. Here we identify phospho-H2AX chromatin domains in the nanometre range with median length of ∼75 kb. Correlation analysis with over 60 genomic features shows a time-dependent euchromatin-to-heterochromatin repair trend...
June 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/28600723/the-3d-protein-of-duck-hepatitis-a-virus-type-1-binds-to-a-viral-genomic-3-utr-and-shows-rna-dependent-rna-polymerase-activity
#12
Yu Zhang, Qianda Cao, Mingshu Wang, Renyong Jia, Shun Chen, Dekang Zhu, Mafeng Liu, Kunfeng Sun, Qiao Yang, Ying Wu, Xinxin Zhao, Xiaoyue Chen, Anchun Cheng
To explore the RNA-dependent RNA polymerase (RdRP) function of the 3D protein of duck hepatitis A virus type 1 (DHAV-1), the gene was cloned into the pET-32a(+) vector for prokaryotic expression. The 3' untranslated region (3' UTR) of DHAV-1 together with a T7 promoter was cloned into the pMD19-T vector for in vitro transcription of 3' UTR RNA, which was further used as a template in RNA-dependent RNA polymerization. In this study, three methods were applied to analyze the RdRP function of the 3D protein: (1) ammonium molybdate spectrophotometry to detect pyrophosphate produced during polymerization; (2) quantitative reverse transcription PCR (RT-qPCR) to investigate the changes in RNA quantity during polymerization; and (3) electrophoresis mobility shift assay to examine the interaction between the 3D protein and 3' UTR...
June 9, 2017: Virus Genes
https://www.readbyqxmd.com/read/28596154/3d-printed-pathological-sectioning-boxes-to-facilitate-radiological-pathological-correlation-in-hepatectomy-cases
#13
Andrew T Trout, Matthew R Batie, Anita Gupta, Rachel M Sheridan, Gregory M Tiao, Alexander J Towbin
Radiogenomics promises to identify tumour imaging features indicative of genomic or proteomic aberrations that can be therapeutically targeted allowing precision personalised therapy. An accurate radiological-pathological correlation is critical to the process of radiogenomic characterisation of tumours. An accurate correlation, however, is difficult to achieve with current pathological sectioning techniques which result in sectioning in non-standard planes. The purpose of this work is to present a technique to standardise hepatic sectioning to facilitateradiological-pathological correlation...
June 8, 2017: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28595570/plant-pectin-acetylesterase-structure-and-function-new-insights-from-bioinformatic-analysis
#14
Florian Philippe, Jérôme Pelloux, Catherine Rayon
BACKGROUND: Pectins are plant cell wall polysaccharides that can be acetylated on C2 and/or C3 of galacturonic acid residues. The degree of acetylation of pectin can be modulated by pectin acetylesterase (EC 3.1.1.6, PAE). The function and structure of plant PAEs remain poorly understood and the role of the fine-tuning of pectin acetylation on cell wall properties has not yet been elucidated. RESULTS: In the present study, a bioinformatic approach was used on 72 plant PAEs from 16 species among 611 plant PAEs available in plant genomic databases...
June 8, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28591736/clinically-relevant-morphological-structures-in-breast-cancer-represent-transcriptionally-distinct-tumor-cell-populations-with-varied-degrees-of-epithelial-mesenchymal-transition-and-cd44-cd24-stemness
#15
Evgeny V Denisov, Nikolay A Skryabin, Tatiana S Gerashchenko, Lubov A Tashireva, Jochen Wilhelm, Mikhail A Buldakov, Aleksei A Sleptcov, Igor N Lebedev, Sergey V Vtorushin, Marina V Zavyalova, Nadezhda V Cherdyntseva, Vladimir M Perelmuter
Intratumor morphological heterogeneity in breast cancer is represented by different morphological structures (tubular, alveolar, solid, trabecular, and discrete) and contributes to poor prognosis; however, the mechanisms involved remain unclear. In this study, we performed 3D imaging, laser microdissection-assisted array comparative genomic hybridization and gene expression microarray analysis of different morphological structures and examined their association with the standard immunohistochemistry scorings and CD44+CD24- cancer stem cells...
May 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28588240/structural-modeling-of-chromatin-integrates-genome-features-and-reveals-chromosome-folding-principle
#16
Wen Jun Xie, Luming Meng, Sirui Liu, Ling Zhang, Xiaoxia Cai, Yi Qin Gao
How chromosomes fold into 3D structures and how genome functions are affected or even controlled by their spatial organization remain challenging questions. Hi-C experiment has provided important structural insights for chromosome, and Hi-C data are used here to construct the 3D chromatin structure which are characterized by two spatially segregated chromatin compartments A and B. By mapping a plethora of genome features onto the constructed 3D chromatin model, we show vividly the close connection between genome properties and the spatial organization of chromatin...
June 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28588198/in-vitro-assembly-of-the-rous-sarcoma-virus-capsid-protein-into-hexamer-tubes-at-physiological-temperature
#17
Soumeya A Jaballah, Graham D Bailey, Ambroise Desfosses, Jaekyung Hyun, Alok K Mitra, Richard L Kingston
During a proteolytically-driven maturation process, the orthoretroviral capsid protein (CA) assembles to form the convex shell that surrounds the viral genome. In some orthoretroviruses, including Rous Sarcoma Virus (RSV), CA carries a short and hydrophobic spacer peptide (SP) at its C-terminus early in the maturation process, which is progressively removed as maturation proceeds. In this work, we show that RSV CA assembles in vitro at near-physiological temperatures, forming hexamer tubes that effectively model the mature capsid surface...
June 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28587976/mechanosensing-of-matrix-by-stem-cells-from-contractility-and-matrix-heterogeneity-to-cardiogenesis-and-muscle-stem-cells
#18
REVIEW
Lucas Smith, Sangkyun Cho, Dennis E Discher
Stem cells are particularly 'plastic' cell types that are induced by various cues to become specialized, tissue-functional lineages by switching on the expression of specific gene programs. Matrix stiffness is among the cues that multiple stem cell types can sense and respond to. This seminar-style review focuses on mechanosensing of matrix elasticity in the differentiation or early maturation of a few illustrative stem cell types, with an intended audience of biologists and physical scientists. Contractile forces applied by a cell's acto-myosin cytoskeleton are often resisted by the extracellular matrix and transduced through adhesions and the cytoskeleton ultimately into the nucleus to modulate gene expression...
June 3, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28579476/modeling-neurodegenerative-diseases-with-patient-derived-induced-pluripotent-cells-possibilities-and-challenges
#19
REVIEW
Anna Poon, Yu Zhang, Abinaya Chandrasekaran, Phetcharat Phanthong, Benjamin Schmid, Troels T Nielsen, Kristine K Freude
The rising prevalence of progressive neurodegenerative diseases coupled with increasing longevity poses an economic burden at individual and societal levels. There is currently no effective cure for the majority of neurodegenerative diseases and disease-affected tissues from patients have been difficult to obtain for research and drug discovery in pre-clinical settings. While the use of animal models has contributed invaluable mechanistic insights and potential therapeutic targets, the translational value of animal models could be further enhanced when combined with in vitro models derived from patient-specific induced pluripotent stem cells (iPSCs) and isogenic controls generated using CRISPR-Cas9 mediated genome editing...
June 2, 2017: New Biotechnology
https://www.readbyqxmd.com/read/28575119/nucleolus-association-of-chromosomal-domains-is-largely-maintained-in-cellular-senescence-despite-massive-nuclear-reorganisation
#20
Stefan Dillinger, Tobias Straub, Attila Németh
Mammalian chromosomes are organized in structural and functional domains of 0.1-10 Mb, which are characterized by high self-association frequencies in the nuclear space and different contact probabilities with nuclear sub-compartments. They exhibit distinct chromatin modification patterns, gene expression levels and replication timing. Recently, nucleolus-associated chromosomal domains (NADs) have been discovered, yet their precise genomic organization and dynamics are still largely unknown. Here, we use nucleolus genomics and single-cell experiments to address these questions in human embryonic fibroblasts during replicative senescence...
2017: PloS One
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