Development of a new reduced order model for predicting the energy savings of multi-ECM permutations
Not Available
Hendricken, Liam↗
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An extracellular matrix (ECM) model at high malignant colorectal tumor increases chondroitin sulfate chains to promote epithelial-mesenchymal transition and chemoresistance acquisition
Highlights: • Effect of ECM dynamics in tumor progression on EMT and chemoresistance were assessed. • 5-FU increased EMT genes and ABCB1 expression via TGF-β signaling. • High malignant tumor ECM promoted EMT and ABCB1 expression via TGF-β signaling. • High malignant tumor ECM possessed chondroitin sulfate chains at high level. • Increased chondroitin sulfate promoted EMT genes and ABCB1 expression. Chemoresistance is one of the major barriers for tumor chemotherapy. It is clinically known that chemoresistance increases during tumor progression. Additionally, the extracellular matrix (ECM) is also remodeled during tumor progression. However, it remains unclear how ECM remodeling contributes to chemoresistance acquisition. Recently, it has been reported that epithelial-mesenchymal transition (EMT) contributes to chemoresistance acquisition. Here, how ECM remodeling contributes to 5-fluorouracil (5-FU) resistance acquisition was investigated from the viewpoints of EMT using in vitro ECM models mimicking native ECM in colorectal tumor tissue at three different malignant levels. 5-FU partially induced EMT and increased ABCB1 in colorectal HT-29 cells via TGF-β signaling (an invasive tumor cell model). When HT-29 cells were cultured on an ECM model (high malignant matrices) mimicking native ECM in highly malignant tumor tissues, the cells facilitated TGF-β-induced EMT and increased ABCB1 upregulation compared with that of other ECM models mimicking the low malignant level and normal tissues. High malignant matrices contained more chondroitin sulfate (CS) chains than those of other ECM models. Finally, CS chain-reduced high malignant matrices could not facilitate ABCB1 upregulation and TGF-β-induced EMT. These results demonstrated that ECM remodeling during tumor progression increased CS chains to facilitate EMT and ABCB1 upregulation, contributing to chemoresistance acquisition.
60 APPLIED LIFE SCIENCES↗
Macrophage infiltration regulates the adipose ECM reconstruction and the fibrosis process after fat grafting
Background: Fat grafting experiences a regeneration process from free lipoaspirate to intact adipose tissue. The adipose extracellular matrixes (ECM) provide the structure and biochemical support for surrounding cells; inflammatory cells, like macrophages, regulate the process. Our hypothesis states that transferred fat undergoes ECM remodeling after fat grafting and this process is regulated by macrophage infiltration. Methods: Lipoaspirate was injected subcutaneously into the back of nude mice. The micro-structure of the fat grafts was observed and evaluated using scanning electron microscope (SEM) and collagen I immunohistostaining. The gene transcription level of collagen proteins and the matrix metalloproteinases (MMPs) were assessed by qRT-PCR. Local injection of clodronate-encapsulated liposome was used to evaluate the role of macrophages of fat grafts at different stages in ECM remodeling, depletion of macrophages, at different time points (Week 1 and Week 4). Results: Results from the SEM analysis showed that liposuction caused severe damage to the ECM structure in freshly aspirated adipose tissue. On Day 1 post-transplantation, the surface of adipocytes was covered with platelets and this secreted fibrin network on the fat grafts. An integral adipose structure was already established with an intact ECM at the end of Week 1. The early depletion of macrophages remarkably hindered ECM reconstruction process by down-regulating the expression of collagen proteins and MMPs. Expression of Collagen I was significantly decreased after depletion of macrophages in both gene and protein levels. Results also showed that the depletion of macrophages at the later stage of fat grafting resulted in less fibrosis and capsule formation. Conclusion: Free fat aspirates undergo a prompt ECM reconstruction process and completed in the first week; this process can be initiated with platelets and mainly modulated by inflammatory cells such as macrophages. It was also observed that prolonged macrophage infiltration contributes to fibrosis and capsule formation in fat grafts. - Highlights: • Free fat aspirates undergo a prompt ECM reconstruction process in the first week. • The ECM reconstruction process is initiated with platelets and modulated by macrophages. • Depletion of macrophage in transferred fat resulted in delayed ECM reconstruction.
60 APPLIED LIFE SCIENCES↗
Correlation between ECM guidance and actin polymerization on osteogenic differentiation of human adipose-derived stem cells
The correlation between extracellular matrix (ECM) components, cell shape, and stem cell guidance can shed light in understanding and mimicking the functionality of stem cell niches for various applications. This interplay on osteogenic guidance of human adipose-derived stem cells (hASCs) was focus of this study. Proliferation and osteogenic markers like alkaline phosphatase activity and calcium mineralization were slightly increased by the ECM components laminin (LA), collagen I (COL), and fibronectin (FIB); with control medium no differentiation occurred. ECM guided differentiation was rather dependent on osterix than on Runx2 pathway. FIB significantly enhanced cell elongation even in presence of actin polymerization blockers cytochalasin D (CytoD) and ROCK inhibitor Y-27632, which generally caused more rounded cells. Except for the COL surface, both inhibitors increased the extent of osterix, while the Runx2 pathway was more sensitive to the culture condition. Both inhibitors did not affect hASC proliferation. CytoD enabled osteogenic differentiation independently from the ECM, while it was rather blocked via Y-27632 treatment; on FIB the general highest extent of differentiation occurred. Taken together, the ECM effect on hASCs occurs indirectly and selectively via a dominant role of FIB: it sustains osteogenic differentiation in case of a tension-dependent control of actin polymerization. - Highlights: • Interplay of ECM and cell shape guides osteogenic differentiation of hASCs. • ECM components only present a promotive but not stimulative effect. • No direct correlation between ECM-enhanced cell elongation and differentiation. • Suppression of differentiation depends on a specific actin polymerization blocking. • Fibronectin sustains cell elongation and differentiation in case of blocking actin.
60 APPLIED LIFE SCIENCES↗
Differences in soil organic matter between EcM- and AM-dominated forests depend on tree and fungal identity
As global change shifts the species composition of forests, we need to understand which species characteristics affect soil organic matter (SOM) cycling to predict future soil carbon (C) storage. Recently, whether a tree species forms a symbiosis with arbuscular (AM) versus ectomycorrhizal (EcM) fungi has been suggested as a strong predictor of soil C storage, but there is wide variability within EcM systems. In this study, we investigated how mycorrhizal associations and the species composition of canopy trees and mycorrhizal fungi related to the proportion of soil C and nitrogen (N) in mineral associations and soil C:N across four sites representing distinct climates and tree communities in the eastern US broadleaf forest biome. In two of our sites, we found the expected relationship of declining mineral-associated C and N and increasing soil C:N ratios as the basal area of EcM-associating trees increased. However, across all sites these soil properties strongly correlated with canopy tree and fungal species composition. Sites where the expected pattern with EcM basal area was observed were (1) dominated by trees with lower quality litter in the Pinaceae and Fagaceae families and (2) dominated by EcM fungi with medium-distance exploration type hyphae, melanized tissues, and the potential to produce peroxidases. Here, this observational study demonstrates that differences in SOM between AM and EcM systems are dependent on the taxa of trees and EcM fungi involved. Important information is lost when the rich mycorrhizal symbiosis is reduced to two categories.
mineral-associated organic matter↗
Shear stress-mediated changes in the expression of complement regulatory protein CD59 on human endothelial progenitor cells by ECM-integrinαVβ3-F-actin pathway in vitro
Highlights: • Shear stress increases the expression of complement regulatory protein CD59 in human EPCs. • Shear stress-induced CD59 expression is closely related to extracellular matrix components. • Shear stress augments the expression of complement regulatory protein CD59 by ECM-integrin-F-actin pathway. Membrane regulatory proteins, such as CD46, CD55, and CD59, prevent excess complement activation and to protect cells from damage. Previous investigations confirmed that shear stress in the physiological range was more favorable for endothelial progenitor cells (EPCs) to repair injured vascular endothelial cells and operates mainly in atheroprotective actions. However, detailed events that contribute to shear stress-induced protection in EPCs, particularly the mechanisms of signal transduction, remain poorly understood. In this study, we observed shear stress-mediated changes in the expression of complement regulatory proteins CD46, CD55, and CD59 on human EPCs and focused on the mechanical transmission mechanism in transformed cells in response to the ECM-F-actin pathway in vitro. Shear stress was observed to promote the expression of complement regulatory protein CD59, but not CD46 or CD55, on EPCs. In addition, the shear stress-induced CD59 expression was confirmed to be associated with the ECM components and was alleviated in EPCs pretreated with GRGDSP, which inhibits ECM components-integrin interaction. Furthermore, shear stress also promotes the rearrangement and polymerization of F-actin. However, shear stress-induced CD59 expression was reduced when the F-actin stress fiber formation process was delayed by Gly-Arg-Gly-Asp-Ser-Pro (GRGDSP) or destroyed by cytochalasin D (Cyto D), while Jasplakinolide (JAS) reversed the expression of CD59 through promotion of F-actin polymerization and its stabilizing capacities. Our results indicates that shear stress is an important mediator in EPC expression of CD59 regulated by the ECM-F-actin pathway, which is a key factor in preventing membrane attack complex (MAC) -mediated cell autolysis.
60 APPLIED LIFE SCIENCES↗
Activin A induces leiomyoma cell proliferation, extracellular matrix (ECM) accumulation and myofibroblastic transformation of myometrial cells via p38 MAPK
Highlights: • Activin A induces accumulation of ECM via the activation of p38 MAPK in HuLM cells. • Activation of p38 MAPK stimulates accumulation of ECM in HuLM cells. • SB202190 attenuates cell proliferation induced by Activin A via inhibit the activation of p38 MAPK in HuLM cells. • SB202190 attenuates deposition of ECM induced by Activin A via inhibit the activation of p38 MAPK in HM cells. • SB202190 interrupts myofibroblast differentiation and functional transformation of mice myometrial cells. The objective of this study was to evaluate the role of Activin A and p38β MAPK-activated signaling in human leiomyoma cells, myometrial cells and mouse myometrial tissues.
60 APPLIED LIFE SCIENCES↗
Local and nonlocal phase-field models of tumor growth and invasion due to ECM degradation
We present and analyze new multi-species phase-field mathematical models of tumor growth and ECM invasion. The local and nonlocal mathematical models describe the evolution of volume fractions of tumor cells, viable cells (proliferative and hypoxic cells), necrotic cells, and the evolution of matrix-degenerative enzyme (MDE) and extracellular matrix (ECM), together with chemotaxis, haptotaxis, apoptosis, nutrient distribution, and cell-to-matrix adhesion. We provide a rigorous proof of the existence of solutions of the coupled system with gradient-based and adhesion-based haptotaxis effects. In addition, we discuss finite element discretizations of the model, and we present the results of numerical experiments designed to show the relative importance and roles of various effects, including cell mobility, proliferation, necrosis, hypoxia, and nutrient concentration on the generation of MDEs and the degradation of the ECM.
Mathematics↗
Analysis of Ground Source Heat Pump ECMs: Implemented Under DOE ESPC IDIQ Contract
Several federal performance and decarbonization objectives are driving the U.S. government to transition to net-zero emissions across the federal building portfolio. The overarching purpose of this Federal Energy Management Program (FEMP)-Geothermal Technologies Office (GTO) work is to support federal facilities in accomplishing the administration’s federal building decarbonization goals. Creating awareness of existing geothermal (or ground-source) heat pump (GHP) systems deployed on federal property, implemented using performance contracts and evaluating the energy and environmental impacts of these systems, this work will assist federal facilities in considering inclusion of GHP technology energy conservation measures (ECMs) in future performance contracting project awards. This report summarizes analyses of data from GHP ECMs installed under the DOE ESPC IDIQ contract across various climate areas and geographic locations, agencies, and building use types. Through the analysis of proposed GHP ECMs and understanding key metrics on implemented GHP systems in a variety of applications, FEMP and GTO can further support federal agencies in meeting decarbonization and net-zero building goals by evaluating and incorporating GHP systems into performance contracts and communicate the benefits of this technology.
15 GEOTHERMAL ENERGY↗
Engineered Containment Mound (ECM) Design for LLRW at CNL in Chalk River, Canada - 19123
The Atomic Energy of Canada Limited has an initiative to transform the Chalk River Laboratory (CRL) facility into an updated research facility to continue nuclear energy and other energy research which is paramount to the continued growth of the energy sector in Canada. The Near Surface Disposal Facility (NSDF) will be licensed by Canadian Nuclear Safety Commission prior to construction and receipt of waste. The NSDF has been designed to allow for disposal of waste in a manner that is protective of the environment and human health. The Engineered Containment Mound (ECM) is a major structure associated with the NSDF design to allow for long-term disposal of 1,000,000 cubic meters of LLRW. This paper describes the design of major components of the ECM: ECM geometry, perimeter berm, base liner system, and cover system. (authors)
12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗
Spindle pole body component 25 homolog expressed by ECM stiffening is required for lung cancer cell proliferation
Highlights: • Matrix stiffness regulates the expression of genes involved in cell proliferation. • SPC25 is identified as hazard gene induced by matrix stiffness. • SPC25 is involved in cancer cell proliferation under stiff matrix conditions. • Depletion of SPC25 induces G2/M arrest via chromosome misalignment in metaphase. Accumulating evidence has shown that matrix stiffening in cancer tissue by the deposition of extracellular matrix (ECM) is closely related with severe tumor progression. However, much less is known about the genes affected by matrix stiffness and its signaling for cancer progression. In the current research, we investigated the differential gene expression of a non-small lung adenocarcinoma cell line, H1299, cultured under the conditions of soft (∼0.5 kPa) and stiff (∼40 kPa) matrices, mimicking the mechanical environments of normal and cancerous tissues, respectively. For integrated transcriptome analysis, the genes identified by ECM stiffening were compared with 8248 genes retrieved from The Cancer Genome Atlas Lung Adenocarcinoma (TCGA). In stiff matrix, 29 genes were significantly upregulated, while 75 genes were downregulated. The screening of hazard ratios for these genes using the Kaplan-Meier Plotter identified 8 genes most closely associated with cancer progression under the condition of matrix stiffening. Among these genes, spindle pole body component 25 homolog (SPC25) was one of the most up-regulated genes in stiff matrix and tumor tissue. Knockdown of SPC25 in H1299 cells using shRNA significantly inhibited cell proliferation with downregulation of the expression of checkpoint protein, Cyclin B1, under the condition of stiff matrix whereas the proliferation rate in soft matrix was not affected by SPC25 silencing. Thus, our findings provide novel key molecules for studying the relationship of extracellular matrix stiffening and cancer progression.
60 APPLIED LIFE SCIENCES↗
Stiffness anisotropy coordinates supracellular contractility driving long-range myotube-ECM alignment
The ability of cells to organize into tissues with proper structure and function requires the effective coordination of proliferation, migration, polarization, and differentiation across length scales. Skeletal muscle is innately anisotropic; however, few biomaterials can emulate mechanical anisotropy to determine its influence on tissue patterning without introducing confounding topography. Here, we demonstrate that substrate stiffness anisotropy coordinates contractility-driven collective cellular dynamics resulting in C2C12 myotube alignment over millimeter-scale distances. When cultured on mechanically anisotropic liquid crystalline polymer networks (LCNs) lacking topography, C2C12 myoblasts collectively polarize in the stiffest direction. Cellular coordination is amplified through reciprocal cell-ECM dynamics that emerge during fusion, driving global myotube-ECM ordering. Conversely, myotube alignment was restricted to small local domains with no directional preference on mechanically isotropic LCNs of the same chemical formulation. These findings provide valuable insights for designing biomaterials that mimic anisotropic microenvironments and underscore the importance of stiffness anisotropy in orchestrating tissue morphogenesis.
59 BASIC BIOLOGICAL SCIENCES↗
Mutant cytoskeletal and ECM peptides sensitive to the ST14 protease are associated with a worse outcome for glioblastoma multiforme
Highlights: • In GBM, mutant ECM proteins appear largely resistant to the ST14 protease. • Patients with resistant proteins have a better survival. • The few patients with sensitive mutants have T-cell infiltrates. We previously identified a set of the most frequently mutated cytoskeleton- and extracellular matrix-related proteins (CECMPs) in numerous cancer datasets. In this report, we used a bioinformatics approach to assess the impact of amino acid (AA) substitutions on the sensitivity of CECMPs to the ST14 protease (matriptase I), a transmembrane serine protease previously implicated in cancer development. Results indicated that AA substitutions in glioblastoma multiforme (GBM) CECMPs are skewed toward increased resistance to the ST14 protease, in comparison to the wild-type peptide sequence. Furthermore, the protease resistant AA substitutions represent relatively high binding affinities to HLA class I proteins, when assessing the binding specificities using HLA class I alleles matched to the source of the mutant AA. Moreover, samples representing AA substitutions that increased protease sensitivity also represented reduced overall and disease-free survival periods for patients with glioblastoma. To assess tumor specimen immunogenicity, we identified T-cell receptor (TCR) V(D)J recombinations in GBM exome files. The overlap between ST14 protease sensitive mutant barcodes and the TCR V(D)J recombination read positive barcodes represented significantly reduced survival.
60 APPLIED LIFE SCIENCES↗
Δ133p53 coordinates ECM-driven morphogenesis and gene expression in 3-dimensional mammary epithelial acini
Growing evidence indicates that p53 has a crucial role in normal tissue development. The role of the canonical p53 (p53α) and its 12± isoforms in development and homeostasis of healthy tissue remains poorly understood. Here we demonstrate that Δ133p53, three short isoforms of p53 isoform, responds specifically to laminin-111 and plays an important regulatory role in formation of mammary organoids in concert with p53α. We demonstrate that down-modulation of Δ133p53 isoforms leads to changes in gene expression of extracellular matrix molecules: fibronectin (FN), EDA+-FN, laminin α5, and laminin α3 in human breast epithelial cells. These changes resulted in increased actin stress fibers and enhanced migratory behavior of cells in 2-dimensional culture. We found that α5β1-integrin coupled with the extracellularly deposited EDA+-FN activates Akt signaling pathway in 3-dimensional (3D) culture when Δ133p53 is dysregulated. Cells that do not express detectable Δ133p53 isoforms or express low levels of these isoforms failed to form polarized structures in 3D. These results uncover that Δ133p53 isoforms coordinate expression and deposition of organ-specific ECM molecules that are critical for maintenance of tissue architecture and function.
Lee, Sun-Young (ORCID:000000034970241X)↗
Optimizing cell encapsulation condition in ECM-Collagen I hydrogels to support 3D neuronal cultures
Not Available
3D Neuronal culture↗
Alterations in ECM signature underscore multiple sub-phenotypes of intervertebral disc degeneration
Not Available
Ohnishi, Takashi↗
Decellularized ECM derived from normal bone involved in the viability and chemo-sensitivity in multiple myeloma cells
Multiple myeloma (MM) is an incurable plasma cell malignancy. The progression of MM is closely related to the bone microenvironment. Bone matrix proteins are remodeled and manipulated to govern cancer growth during the process of MM. However the role of normal bone extracellular matrix in MM is still unclear. In this study the decellularized extracellular matrix derived from normal SD rats’ skulls (N-dECM) was prepared by decellularization technology. The CCK 8 assay and the dead-live cell kit assay were used to determine the viability of MM cells and the sensitivity to bortezomib. The Realtime PCR and Western blot assay were used to assay the mRNA and protein related to MM. Under the treatment of N-dECM, we found that the viability of MM cells was inhibited and the sensitivity of MM cells to bortezomib was increased. Additionally, the expression levels of APRIL and TACI, which participated in the progression of MM, were significantly decreased in MM cells. It suggested that N-dECM might inhibit the development of MM via APRIL-TACI axis, and our study may provide a novel and potential biomaterial for MM therapy.
60 APPLIED LIFE SCIENCES↗
Development of a simplified calibrated building simulation model of a supermarket for proposed ECMs and control strategies impact evaluation
Calibrated building energy simulation is an important pathway to more energy-efficient buildings, but the information requirements of some approaches to this problem are significant. This is particularly true for supermarkets and other so-called “big-box” retail stores. Another characteristic of supermarkets is the significant interaction between Heating Ventilating and Air Conditioning (HVAC) and refrigeration systems in these buildings. These buildings could contain a wide variety of systems and a degree of load diversity that makes calibrated modeling a challenge. This paper describes a simplified approach that uses OpenStudio and EnergyPlus to combine known building parameters with “typical” parameters, resulting in a simplified building that is amenable to calibration. This approach was applied to a big-box store located in Nashville, Tennessee, and a calibrated model was obtained that was used to study potential energy conservation measures. Further, the paper also explores the capabilities of whole-building energy modeling tools, such as EnergyPlus, for modeling the HVAC controls and sequences and their impact evaluation. Although some measures are precluded by the model simplicity, several measures were found to improve the efficiency of the model and demonstrate that the simplified modeling approach is effective. Practical Application: This paper introduces a hybrid approach of building energy model calibration using limited information available from the actual building in combination with characteristics of a “typical” building of the same type. This hybrid approach would also be applicable for other building types than discussed in this paper to calibrate the building energy model using limited information from the actual building.
42 ENGINEERING↗