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Integrative Biology: Quantitative Biosciences From Nano to Macro

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https://read.qxmd.com/read/30722034/precision-immunoprofiling-to-reveal-diagnostic-signatures-for-latent-tuberculosis-infection-and-reactivation-risk-stratification
#1
Heather M Robison, Patricio Escalante, Enrique Valera, Courtney L Erskine, Loretta Auvil, Humberto C Sasieta, Colleen Bushell, Michael Welge, Ryan C Bailey
Latent tuberculosis infection (LTBI) is estimated in nearly one quarter of the world's population, and of those immunocompetent and infected ~10% will proceed to active tuberculosis (TB). Current diagnostics cannot definitively identify LTBI and provide no insight into reactivation risk, thereby defining an unmet diagnostic challenge of incredible global significance. We introduce a new machine-learning-driven approach to LTBI diagnostics that leverages a high throughput, multiplexed cytokine detection technology and powerful bioinformatics to reveal multi-marker signatures for LTBI diagnosis and risk stratification...
February 4, 2019: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://read.qxmd.com/read/30516771/protein-structure-networks-provide-insight-into-active-site-flexibility-in-esterase-lipases-from-the-carnivorous-plant-drosera-capensis
#2
Vy T Duong, Megha H Unhelkar, John E Kelly, Suhn H Kim, Carter T Butts, Rachel W Martin
In plants, esterase/lipases perform transesterification reactions, playing an important role in the synthesis of useful molecules, such as those comprising the waxy coatings of leaf surfaces. Plant genomes and transcriptomes have provided a wealth of data about expression patterns and the circumstances under which these enzymes are upregulated, e.g. pathogen defense and response to drought; however, predicting their functional characteristics from genomic or transcriptome data is challenging due to weak sequence conservation among the diverse members of this group...
December 5, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://read.qxmd.com/read/30565615/back-cover
#3
(no author information available yet)
No abstract text is available yet for this article.
December 19, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://read.qxmd.com/read/30565611/front-cover
#4
(no author information available yet)
No abstract text is available yet for this article.
December 19, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://read.qxmd.com/read/30565606/contents-list
#5
(no author information available yet)
No abstract text is available yet for this article.
December 19, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://read.qxmd.com/read/30520487/enhanced-intrinsic-cyp3a4-activity-in-human-hepatic-c3a-cells-with-optically-controlled-crispr-dcas9-activator-complex
#6
Shuo Han, Shiruo Wei, Xuan Wang, Xu Han, Mingzhi Zhang, Ming Su, Yang Li, Jinhai Guo, Wotan Zeng, Jinwen Liu, Yi Gao, Li Shen
Human hepatic C3A cells have been applied in bioartificial liver development, although these cells display low intrinsic cytochrome P450 3A4 (CYP3A4) enzyme activity. We aimed to enhance CYP3A4 enzyme activity of C3A cells utilizing CRISPR gene editing technology. We designed two CYP3A4 expression enhanced systems applying clustered regularly interspaced short palindromic repeats (CRISPR) gene technology: a CRISPR-on activation system including dCas9-VP64-GFP and two U6-sgRNA-mCherry elements, and a light-controlled CRISPR-on activation system combining our CRISPR-on activation system with an optical control system to facilitate regulation of CYP3A4 expression for various applications...
December 19, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://read.qxmd.com/read/30420987/morphology-based-prediction-of-cancer-cell-migration-using-an-artificial-neural-network-and-a-random-decision-forest
#7
Zhixiong Zhang, Lili Chen, Brock Humphries, Riley Brien, Max S Wicha, Kathryn E Luker, Gary D Luker, Yu-Chih Chen, Euisik Yoon
Metastasis is the cause of death in most patients of breast cancer and other solid malignancies. Identification of cancer cells with highly migratory capability to metastasize relies on markers for epithelial-to-mesenchymal transition (EMT), a process increasing cell migration and metastasis. Marker-based approaches are limited by inconsistences among patients, types of cancer, and partial EMT states. Alternatively, we analyzed cancer cell migration behavior using computer vision. Using a microfluidic single-cell migration chip and high-content imaging, we extracted morphological features and recorded migratory direction and speed of breast cancer cells...
November 13, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://read.qxmd.com/read/30328449/shear-stress-induces-expression-intracellular-reorganization-and-enhanced-notch-activation-potential-of-jagged1
#8
R C H Driessen, O M J A Stassen, M Sjöqvist, F Suarez Rodriguez, J Grolleman, C V C Bouten, C M Sahlgren
Notch signaling and blood flow regulate vascular formation and maturation, but how shear stress affects the different components of the Notch pathway in endothelial cells is poorly understood. We show that laminar shear stress results in a ligand specific gene expression profile in endothelial cells (HUVEC). JAG1 expression increases while DLL4 expression decreases. Jagged1 shows a unique response by clustering intracellularly six to nine hours after the onset of flow. The formation of the Jagged1 clusters requires protein production, ER export and endocytosis...
November 12, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://read.qxmd.com/read/30320857/transfer-of-assembled-collagen-fibrils-to-flexible-substrates-for-mechanically-tunable-contact-guidance-cues
#9
Juan Wang, Joseph Koelbl, Anuraag Boddupalli, Zhiqi Yao, Kaitlin M Bratlie, Ian C Schneider
Contact guidance or bidirectional migration along aligned fibers modulates many physiological and pathological processes such as wound healing and cancer invasion. Aligned 2D collagen fibrils epitaxially grown on mica substrates replicate many features of contact guidance seen in aligned 3D collagen fiber networks. However, these 2D collagen self-assembled substrates are difficult to image through, do not have known or tunable mechanical properties and cells degrade and mechanically detach collagen fibrils from the surface, leading to an inability to assess contact guidance over long times...
November 12, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://read.qxmd.com/read/30295307/chemical-modification-of-enveloped-viruses-for-biomedical-applications
#10
REVIEW
Pahweenvaj Ratnatilaka Na Bhuket, Jittima Amie Luckanagul, Pornchai Rojsitthisak, Qian Wang
The unique characteristics of enveloped viruses including nanometer size, consistent morphology, narrow size distribution, versatile functionality and biocompatibility have attracted attention from scientists to develop enveloped viruses for biomedical applications. The biomedical applications of the viral-based nanoparticles include vaccine development, imaging and targeted drug delivery. The modification of the structural elements of enveloped viruses is necessary for the desired functions. Here, we review the chemical approaches that have been utilized to develop bionanomaterials based on enveloped viruses for biomedical applications...
November 12, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://read.qxmd.com/read/30295300/engineered-basement-membranes-from-in-vivo-considerations-to-cell-based-assays
#11
REVIEW
Guillaume Perry, Wenjin Xiao, Gavin I Welsh, Adam W Perriman, Rachel Lennon
Improvements in the physiological relevance of cell-based assays have been enabled by the development of various interdisciplinary methods. However, due to their complexity, in vivo structures such as basement membranes (BMs), which regulate the phenotype of adherent cells, are still difficult to mimic in vitro. The reconstruction of a physiologically relevant BM is crucially important to develop cell-based assays with the capacity for drug screening and disease modelling. Here, we review the biophysical and biochemical properties of BMs in vivo and their interactions with neighbouring cells...
November 12, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://read.qxmd.com/read/30281048/phosphatidylcholine-in-the-groove-of-endothelial-cell-protein-c-receptor-epcr-regulates-epcr-conformation-and-protein-c-recognition
#12
Ramesh Prasad, Prosenjit Sen
Endothelial cell protein C receptor (EPCR), the cellular receptor for protein C (PC), facilitates PC activation through the thrombin/thrombomodulin complex and regulates thrombin generation. Under pathophysiological conditions like sepsis, the interactions between EPCR and PC become impaired. Previous studies have demonstrated that the EPCR contains a phospholipid in the antigen-binding groove that is responsible for the structural stability of the EPCR and for PC recognition. However, an understanding at the atomic level during ligand recognition is not fully developed...
November 12, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://read.qxmd.com/read/30398503/an-adhesion-based-approach-for-the-detection-of-esophageal-cancer
#13
Mahboubeh S Noori, Evan S Streator, Grady E Carlson, David S Drozek, Monica M Burdick, Douglas J Goetz
Esophageal cancer has a 5 year survival rate of ∼20%. This dismal prognosis is due, in part, to the fact that esophageal cancer often presents at a late stage. Thus, there is a critical need for assays that enable the early detection of cancerous tissue within the esophagus. The luminal surface of the esophagus expresses signature molecule(s) at sites of transformation providing an avenue for the development of in situ assays that detect neoplastic growth within the esophagus. An attractive approach, receiving increased attention, is the endoscopic administration of particles conjugated with ligands to signature molecules present on transforming tissue...
November 6, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://read.qxmd.com/read/30382278/substrate-stiffness-heterogeneities-disrupt-endothelial-barrier-integrity-in-a-micropillar-model-of-heterogeneous-vascular-stiffening
#14
Jacob A VanderBurgh, Halie Hotchkiss, Archit Potharazu, Paul V Taufalele, Cynthia A Reinhart-King
Intimal stiffening has been linked with increased vascular permeability and leukocyte transmigration, hallmarks of atherosclerosis. However, recent evidence indicates age-related intimal stiffening is not uniform but rather characterized by increased point-to-point heterogeneity in subendothelial matrix stiffness, the impact of which is much less understood. To investigate the impact of spatially heterogeneous matrix rigidity on endothelial monolayer integrity, we develop a micropillar model to introduce closely-spaced, step-changes in substrate rigidity and compare endothelial monolayer phenotype to rigidity-matched, uniformly stiff and compliant substrates...
November 1, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://read.qxmd.com/read/30225509/towards-organogenesis-and-morphogenesis-in-vitro-harnessing-engineered-microenvironment-and-autonomous-behaviors-of-pluripotent-stem-cells
#15
REVIEW
Ningwei Li, Tianfa Xie, Yubing Sun
Recently, researchers have been attempting to control pluripotent stem cell fate or generate self-organized tissues from stem cells. Advances in bioengineering enable generation of organotypic structures, which capture the cellular components, spatial cell organization and even some functions of tissues or organs in development. However, only a few engineering tools have been utilized to regulate the formation and organization of spatially complex tissues derived from stem cells. Here, we provide a review of recent progress in the culture of organotypic structures in vitro, focusing on how microengineering approaches including geometric confinement, extracellular matrix (ECM) property modulation, spatially controlled biochemical factors, and external forces, can be utilized to generate organotypic structures...
October 15, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://read.qxmd.com/read/30225469/quantitative-temporal-interrogation-in-3d-of-bioengineered-human-cartilage-using-multimodal-label-free-imaging
#16
Catarina Costa Moura, Stuart A Lanham, Tual Monfort, Konstantinos N Bourdakos, Rahul S Tare, Richard O C Oreffo, Sumeet Mahajan
The unique properties of skeletal stem cells have attracted significant attention in the development of strategies for skeletal regeneration. However, there remains a crucial unmet need to develop quantitative tools to elucidate skeletal cell development and monitor the formation of regenerated tissues using non-destructive techniques in 3D. Label-free methods such as coherent anti-Stokes Raman scattering (CARS), second harmonic generation (SHG) and two-photon excited auto-fluorescence (TPEAF) microscopy are minimally invasive, non-destructive, and present new powerful alternatives to conventional imaging techniques...
October 15, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://read.qxmd.com/read/30206629/computational-model-of-wound-healing-egf-secreted-by-fibroblasts-promotes-delayed-re-epithelialization-of-epithelial-keratinocytes
#17
Vivi Andasari, Dongyuan Lü, Maciej Swat, Shiliang Feng, Fabian Spill, Li Chen, Xiangdong Luo, Muhammad Zaman, Mian Long
It is widely agreed that keratinocyte migration plays a crucial role in wound re-epithelialization. Defects in this function contribute to wound reoccurrence causing significant clinical problems. Several in vitro studies have shown that the speed of migrating keratinocytes can be regulated by epidermal growth factor (EGF) which affects keratinocyte's integrin expression. The relationship between integrin expression (through cell-matrix adhesion) stimulated by EGF and keratinocyte migration speed is not linear since increased adhesion, due to increased integrin expression, has been experimentally shown to slow down cell migration due to the biphasic dependence of cell speed on adhesion...
October 15, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://read.qxmd.com/read/30187065/direct-immunoassays-and-their-performance-theoretical-modelling-of-the-effects-of-antibody-orientation-and-associated-kinetics
#18
Dana Mackey, Eilís Kelly, Robert Nooney, Richard O'Kennedy
The orientation and activity of antibodies immobilized on solid surfaces are of direct relevance to many immunosensing applications. We therefore investigate a mathematical model which estimates the fraction of antibodies which are available for reaction in a randomly adsorbed sample. Numerical simulations are presented which highlight the separate effects of antibody orientation, accessibility and loss of binding ability on the amount of captured antigen. The assay response can then be expressed as a function of total antibody density and used for optimizing the surface coverage strategy under various conditions...
October 15, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://read.qxmd.com/read/30176029/effect-of-macromolecular-crowding-on-the-kinetics-of-glycolytic-enzymes-and-the-behaviour-of-glycolysis-in-yeast
#19
Henrik S Thoke, Luis A Bagatolli, Lars F Olsen
Water is involved in all aspects of biological activity, both as a solvent and as a reactant. It is hypothesized that intracellular water is in a highly structured state due to the high concentrations of macromolecules in the cell and that this may change the activity of intracellular enzymes due to altered binding affinities and allosteric regulations. Here we first investigate the kinetics of two glycolytic enzymes in artificially crowded aqueous solutions and show that crowding does indeed change their kinetics...
October 15, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://read.qxmd.com/read/30229251/structural-insights-and-influence-of-v599-mutations-on-the-overall-dynamics-of-braf-protein-against-its-kinase-domains
#20
Mayank, Navneet Kaur, Narinder Singh
Mutations in the BRAF gene are well known for their oncogenic effects. Point mutations in V599 are particularly oncogenic and are considered important for therapeutic purposes. Along with wild type, other V599 mutated BRAF variants viz. V599E, V599D and V599R are reported and crystals of the former two with inhibitor (BAY43-9006) are further detailed. Both wild-type and mutated BRAF forms show similar interaction patterns with BAY43-9006, but the 599th residue did not show any involvement in the interactions...
September 19, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
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