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Integrative Biology: Quantitative Biosciences From Nano to Macro

Erdem Kucukal, Jane A Little, Umut A Gurkan
Non-adherence and deformability are the key intrinsic biomechanical features of the red blood cell (RBC), which allow it to tightly squeeze and pass through even the narrowest of microcirculatory networks. Blockage of microcirculatory flow, also known as vaso-occlusion, is a consequence of abnormal cellular adhesion to the vascular endothelium. In sickle cell disease (SCD), an inherited anaemia, even though RBCs have been shown to be heterogeneous in adhesiveness and deformability, this has not been studied in the context of physiologically relevant dynamic shear gradients at the microscale...
March 20, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
Paola Occhetta, Giuseppe Isu, Marta Lemme, Chiara Conficconi, Philipp Oertle, Christian Räz, Roberta Visone, Giulia Cerino, Marija Plodinec, Marco Rasponi, Anna Marsano
In vitro cardiac models able to mimic the fibrotic process are paramount to develop an effective anti-fibrosis therapy that can regulate fibroblast behaviour upon myocardial injury. In previously developed in vitro models, typical fibrosis features were induced by using scar-like stiffness substrates and/or potent morphogen supplementation in monolayer cultures. In our model, we aimed to mimic in vitro a fibrosis-like environment by applying cyclic stretching of cardiac fibroblasts embedded in three-dimensional fibrin-hydrogels alone...
March 13, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
Abdullah A Mosabbir, Anam Qudrat, Kevin Truong
As monoclonal antibodies have two epitopes for their target ligand, they should theoretically dimerize target receptors upon binding. In particular, the dimerization of the vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2) stimulates early events occurring within minutes (e.g. Ca2+ signal generation) and late events occurring over hours and days (e.g. cell migration in angiogenesis). Although studies have noted that antibodies targeting VEGFR2 (anti-VEGFR2) inhibited cell migration in angiogenesis, we show in this paper that an anti-VEGFR2 stimulus nevertheless triggered a Ca2+ signal in VEGFR2 expressing cells...
March 5, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
Natalia Bourguignon, Carolina Attallah, Paola Karp, Ross Booth, Ana Peñaherrera, Cristian Payés, Marcos Oggero, Maximiliano S Pérez, Gustavo Helguera, Betiana Lerner
Herein, a microfluidic device with cistern design for cultivation of adherent eukaryotic cells for the production of recombinant proteins is presented. The geometric configuration of the microchannels in the device provided laminar flow with reduced velocity profiles in the cisterns, resulting in an adequate microenvironment for long-term adherent cell growth with passive pumping flow cycles of 24 hours. CHO-ahIFNα2b and HEK-ahIFNα2b adherent cell lines expressing a novel anti-hIFN-α2b recombinant monoclonal antibody (MAb) for the treatment of systemic lupus erythematosus were cultured on the surface of PDMS/glass microchannels coated with poly-d-lysine...
February 28, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
Shuyu Liu, Yan Tan
A novel and label-free, gold nanorods (GNRs)-based resonance light scattering system assay has been developed for the detection of microalgae superoxide dismutase (SOD). The method relies on the fact that interactions between microalgae SOD and GNRs can emit strong fluorescence signals. The prepared GNRs were well dispersed in the solution and intracellular SOD was extracted from Microcystis aeruginosa; the SOD was then absorbed on the surface of the GNRs. The results demonstrated that the intensity of the fluorescence signals increased at 595 nm with an increase in the SOD concentration, the optimum pH value was concluded to be 7...
February 26, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
Bianca N Lourenço, Nora L Springer, Daniel Ferreira, Carla Oliveira, Pedro L Granja, Claudia Fischbach
CD44, an abundantly expressed adhesion molecule, and its alternative splice variants have been associated with tumorigenesis and metastasis. In the context of gastric cancer (GC), de novo expression of CD44 variant 6 (CD44v6) is found in more than 60% of GCs, but its role in the pathogenesis and progression of this type of cancer remains unclear. Using a combination of media conditioning experiments and decellularized extracellular matrices (ECMs), this study investigates the hypothesis that CD44v6 overexpression enhances tumor cell malignant behavior by modulating stromal cell-mediated ECM remodeling...
February 16, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
V Onesto, R Narducci, F Amato, L Cancedda, F Gentile
We present a mathematical model that quantifies the amount of information exchanged in bi-dimensional networks of nerve cells as a function of network connectivity Q. Upon varying Q over a significant range, we found that, from a certain cell density onwards, 90% of the maximal information transferred I(Q) in a random neuronal network is already reached with just 40% of the total possible connections Q among the cells. As a consequence, the system would not benefit from additional connections in terms of the amount of I(Q), in agreement with the tendency of brains to minimize Q because of its energetic costs...
February 2, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
Joyce W Kamande, Maria A M Lindell, Małgorzata A Witek, Peter M Voorhees, Steven A Soper
Blood samples from patients with plasma cell disorders were analysed for the presence of circulating plasma cells (CPCs) using a microfluidic device modified with monoclonal anti-CD138 antibodies. CPCs were immuno-phenotyped using a CD38/CD56/CD45 panel and identified in 78% of patients with monoclonal gammopathy of undetermined significance (MGUS), all patients with smouldering and symptomatic multiple myeloma (MM), and none in the controls. The burden of CPCs was higher in patients with symptomatic MM compared with MGUS and smouldering MM (p < 0...
January 26, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
Yazdan Asgari, Pegah Khosravi, Zahra Zabihinpour, Mahnaz Habibi
Genome-scale metabolic models have provided valuable resources for exploring changes in metabolism under normal and cancer conditions. However, metabolism itself is strongly linked to gene expression, so integration of gene expression data into metabolic models might improve the detection of genes involved in the control of tumor progression. Herein, we considered gene expression data as extra constraints to enhance the predictive powers of metabolic models. We reconstructed genome-scale metabolic models for lung and prostate, under normal and cancer conditions to detect the major genes associated with critical subsystems during tumor development...
January 19, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
Arja Ray, Rachel K Morford, Nima Ghaderi, David J Odde, Paolo P Provenzano
Carcinoma cells frequently expand and invade from a confined lesion, or multicellular clusters, into and through the stroma on the path to metastasis, often with an efficiency dictated by the architecture and composition of the microenvironment. Specifically, in desmoplastic carcinomas such as those of the breast, aligned collagen tracks provide contact guidance cues for directed cancer cell invasion. Yet, the evolving dynamics of this process of invasion remains poorly understood, in part due to difficulties in continuously capturing both spatial and temporal heterogeneity and progression to invasion in experimental systems...
January 17, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
Chunhe Li
Landscape approaches have been exploited to study the stochastic dynamics of gene networks. However, how to calculate the landscape with a wide range of parameter variations and how to investigate the influence of the network topology on the global properties of gene networks remain to be elucidated. Here, I developed an approach for the landscape of random parameter perturbation (LRPP) to address this issue. Based on a self-consistent approximation approach, by making perturbations to parameters in a given range, I obtained the landscape for gene network systems...
January 17, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
Emilio Satoshi Hara, Masahiro Okada, Noriyuki Nagaoka, Takako Hattori, Letycia Mary Iida, Takuo Kuboki, Takayoshi Nakano, Takuya Matsumoto
Analysis of tissue development from multidisciplinary approaches can result in more integrative biological findings, and can eventually allow the development of more effective bioengineering methods. In this study, we analyzed the initial steps of mineral formation during secondary ossification of mouse femur based on biological and bioengineering approaches. We first found that some chondrocytes burst near the mineralized area. External factors that could trigger chondrocyte burst were then investigated. Chondrocyte burst was shown to be modulated by mechanical and osmotic pressure...
January 15, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
M C Letizia, M Cornaglia, G Tranchida, R Trouillon, M A M Gijs
When studying the drug effectiveness towards a target model, one should distinguish the effects of the drug itself and of all the other factors that could influence the screening outcome. This comprehensive knowledge is crucial, especially when model organisms are used to study the drug effect at a systemic level, as a higher number of factors can influence the drug-testing outcome. Covering the entire experimental domain and studying the effect of the simultaneous change in several factors would require numerous experiments, which are costly and time-consuming...
January 15, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
Lindsay E Clegg, Feilim Mac Gabhann
Inducing therapeutic angiogenesis to effectively form hierarchical, non-leaky networks of perfused vessels in tissue engineering applications and ischemic disease remains an unmet challenge, despite extensive research and multiple clinical trials. Here, we use a previously-developed, multi-scale, computational systems pharmacology model of human peripheral artery disease to screen a diverse array of promising pro-angiogenic strategies, including gene therapy, biomaterials, and antibodies. Our previously-validated model explicitly accounts for VEGF immobilization, Neuropilin-1 binding, and weak activation of VEGF receptor 2 (VEGFR2) by the "VEGFxxxb" isoforms...
January 12, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
Zhisong Wang
Many motor proteins achieve high efficiency for chemomechanical conversion, and single-molecule force-resisting experiments are a major tool to detect the chemomechanical coupling of efficient motors. Here, we introduce several quantitative relations that involve only parameters extracted from force-resisting experiments and offer new benchmarks beyond mere efficiency to judge the chemomechanical optimality or deficit of evolutionary remote motors on the same footing. The relations are verified by the experimental data from F1-ATPase, kinesin-1, myosin V and cytoplasmic dynein, which are representative members of four motor protein families...
January 3, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
Hui Hui Chai, Yao Lu, Can Fang, Ya Dan Li, Yue Jun Kang, Chang Ming Li, Ling Yu
Seed germination is an important means of evaluating seed quality. In the present study, a well array for a seed germination experiment was designed and fabricated by 3D printing for the first time. Each hollow cone-shaped well can hold one seed, which not only prevented the seed from falling out of the well but also ensured that part of the seed was fully exposed to the sublayer of wet filter paper, allowing it to receive water for germination. Coupled with a 3D-printed seed planter, single seeds can be quickly placed into arrayed wells...
January 22, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
Alessio Fanti, Leandro Gammuto, Fabio Mavelli, Pasquale Stano, Roberto Marangoni
A key process of protocell behaviour is their recursive growth and division. In order to be sustainable, the latter must be characterized by an even and homogeneous partition of the solute molecules initially present in the parent protocell among the daughter ones. Here we have investigated, by means of an artificial division model (extrusion of giant lipid vesicles) and confocal microscopy, the fate of solutes when a large vesicle fragments into many smaller vesicles. Solutes of low- and high-molecular weight such as pyranine, calcein, albumin-FITC, dextran-FITC and carbonic anhydrase have been employed...
January 22, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
N Peela, E S Barrientos, D Truong, G Mouneimne, M Nikkhah
Metastatic cancer is regarded as one of the largest contributors to disease-related deaths worldwide. Poor patient prognosis and treatment outcome is tied to the lack of efficacious anti-cancer therapies, which is due in part to the lack of physiologically relevant in vitro screening systems that can mimic the native tumor microenvironment. Conventional drug-screening platforms, which are often used in the pharmaceutical industry, are either two-dimensional (2D) assays or three-dimensional (3D) hydrogel-based matrices that lack precise control over cell distribution, matrix architecture, and organization...
December 11, 2017: Integrative Biology: Quantitative Biosciences From Nano to Macro
A Rolong, E M Schmelz, R V Davalos
We explored the use of irreversible electroporation (IRE) and high-frequency irreversible electroporation (H-FIRE) to induce cell death of tumor-initiating cells using a mouse ovarian surface epithelial (MOSE) cancer model. Tumor-initiating cells (TICs) can be successfully destroyed using pulsed electric field parameters common to irreversible electroporation protocols. Additionally, high-frequency pulses seem to induce cell death of TICs at significantly lower electric fields suggesting H-FIRE can be used to selectively target TICs and malignant late-stage cells while sparing the non-malignant cells in the surrounding tissue...
December 11, 2017: Integrative Biology: Quantitative Biosciences From Nano to Macro
Surapon N Charoensook, Damian J Williams, Syandan Chakraborty, Kam W Leong, Gordana Vunjak-Novakovic
In vitro models of the neuromuscular junction (NMJ) are emerging as a valuable tool to study synaptogenesis, synaptic maintenance, and pathogenesis of neurodegenerative diseases. Many models have previously been developed using a variety of cell sources for skeletal muscle and motoneurons. These models can advanced by integrating beneficial features of the native developmental milieu of the NMJ. We created a functional in vitro model of NMJ by bioreactor cultivation of transdifferentiated myocytes and stem cell-derived motoneurons, in the presence of electrical stimulation...
December 11, 2017: Integrative Biology: Quantitative Biosciences From Nano to Macro
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