The Experts below are selected from a list of 180369 Experts worldwide ranked by ideXlab platform
Arne Traulsen - One of the best experts on this subject based on the ideXlab platform.
-
should Tissue Structure suppress or amplify selection to minimize cancer risk
Biology Direct, 2016Co-Authors: Laura Hindersin, Benjamin Werner, David Dingli, Arne TraulsenAbstract:It has been frequently argued that Tissues evolved to suppress the accumulation of growth enhancing cancer inducing mutations. A prominent example is the hierarchical Structure of Tissues with high cell turnover, where a small number of Tissue specific stem cells produces a large number of specialized progeny during multiple differentiation steps. Another well known mechanism is the spatial organization of stem cell populations and it is thought that this organization suppresses fitness enhancing mutations. However, in small populations the suppression of advantageous mutations typically also implies an increased accumulation of deleterious mutations. Thus, it becomes an important question whether the suppression of potentially few advantageous mutations outweighs the combined effects of many deleterious mutations. We argue that the distribution of mutant fitness effects, e.g. the probability to hit a strong driver compared to many deleterious mutations, is crucial for the optimal organization of a cancer suppressing Tissue architecture and should be taken into account in arguments for the evolution of such Tissues. We show that for systems that are composed of few cells reflecting the typical organization of a stem cell niche, amplification or suppression of selection can arise from subtle changes in the architecture. Moreover, we discuss special Tissue Structures that can suppress most types of non-neutral mutations simultaneously. This article was reviewed by Benjamin Allen, Andreas Deutsch and Ignacio Rodriguez-Brenes. For the full reviews, please go to the Reviewers’ comments section.
-
should Tissue Structure suppress or amplify selection to minimize cancer risk
bioRxiv, 2016Co-Authors: Laura Hindersin, Benjamin Werner, David Dingli, Arne TraulsenAbstract:It has been frequently argued that Tissues evolved to suppress the accumulation of growth enhancing cancer inducing mutations. A prominent example is the hierarchical Structure of Tissues with high cell turnover, where a small number of Tissue specific stem cells produces a large number of specialised progeny during multiple differentiation steps. Another well known mechanism is the spatial organisation of stem cell populations and it is thought that this organisation suppresses fitness enhancing mutations. However, in small populations the suppression of advantageous mutations typically also implies an increased accumulation of deleterious mutations. Thus, it becomes an important question whether the suppression of potentially few advantageous mutations outweighs the combined effects of many deleterious mutations. We argue that the distribution of mutant fitness effects, e.g. the probability to hit a strong driver compared to many deleterious mutations, is crucial for the optimal organisation of a cancer suppressing Tissue architecture and should be taken into account in arguments for the evolution of such Tissues. We show that for systems that are composed of few cells reflecting the typical organisation of a stem cell niche, amplification or suppression of selection can arise from subtle changes in the architecture. Moreover, we discuss special Tissue Structures that can suppress most types of non-neutral mutations simultaneously.
S Takai - One of the best experts on this subject based on the ideXlab platform.
-
MECHANICAL PROPERTIES OF SOFT-Tissue Structure OF KNEE SLEEVE IN FLEXION AND EXTENSION DURING TKA
2018Co-Authors: Tokifumi Majima, S Matsui, O Nishiike, Kenji Takahashi, Y Oshima, N Iizawa, S TakaiAbstract:IntroductionIn order to achieve good clinical results in TKA, soft Tissue balance is important. Soft Tissue balance is closely related to knee kinematics which affects clinical results.Modified gap...
-
mechanical properties of soft Tissue Structure of knee sleeve in flexion and extension during tka
Journal of Bone and Joint Surgery-british Volume, 2017Co-Authors: Tokifumi Majima, S Matsui, O Nishiike, Kenji Takahashi, Y Oshima, N Iizawa, S TakaiAbstract:Introduction In order to achieve good clinical results in TKA, soft Tissue balance is important. Soft Tissue balance is closely related to knee kinematics which affects clinical results. Modified gap balancing technique is one of the standard techniques for posterior stabilized (PS) TKA. On the other hand, appropriate load for the measurement of gap balance has not been established. The purpose of the present study is to measure the mechanical properties of soft Tissue Structure of knee sleeve in flexion and extension during PS TKA using newly developed balancer. The understanding of the mechanical properties is crucial. In particular if these properties are used as input for surgical procedures, standard technique for many surgeons will be established. Materials and Methods Medial compartmental osteoarthrosis (OA) patients (13 female and 7 male) were evaluated. Average age, BMI, and Varus deformity were 72.1 years, 26.9, and 12 degrees, respectively. The newly developed center paddle balancer consists of a built-in spring (Fig. 1). Figure 2 shows the sequence of surgery and measurements. In the surgery, we measured the balance (degrees in Figure 1, A) and distance (mm in Figure 1, B) in extension with a load (Figure 1,C) at transition zone of toe region to linear region. Then, applying the load until flexion gap was the same as that in extension with a patella reduction, we measured the femoral component rotation from the balancer (degrees in Figure 1, A). The anterior and posterior femoral cuts were performed according to measured femoral component rotation which angle is parallel to tibial cut surface. Results Load deformation curves of a knee sleeve Structures showed toe and linear regions. The average stability range (transition zone of toe region to linear region) is 150 to 160N in extension and 130 to 140N in flexion. The distance of stability range between tibia and femur in extension is almost the same as the thickness of tibial component and femoral component (21mm). The distance of stability range between the tibia and femur in flexion is the same as the thickness of tibial component (10mm). Discussion In the present study, load deformation curves of knee sleeve Structures showed bimodal patterns that is the same as ligaments and tendons. It has been reported that a load on ligament is below the transition zone during 80% of normal daily activity. The results indicated that the so called “palpable endpoint” is stability range. According to the present data, we propose a standard modified gap balance technique in PS TKA for medial compartmental OA. The ligament balance is confirmed in extension with 160N of distracting force after soft Tissue release and distal femur and proximal tibial cut. The femoral component rotation is then decided with the load that will open the distance to the thickness of the tibial component in flexion.
Mark D Does - One of the best experts on this subject based on the ideXlab platform.
-
characterization of Tissue Structure at varying length scales using temporal diffusion spectroscopy
NMR in Biomedicine, 2010Co-Authors: John C Gore, Junzhong Xu, Daniel C Colvin, Thomas E Yankeelov, Edward C Parsons, Mark D DoesAbstract:The concepts, theoretical behavior and experimental applications of temporal diffusion spectroscopy are reviewed and illustrated. Temporal diffusion spectra are obtained using oscillating-gradient waveforms in diffusion-weighted measurements, and represent the manner in which various spectral components of molecular velocity correlations vary in different geometrical Structures that restrict or hinder free movements. Measurements made at different gradient frequencies reveal information on the scale of restrictions or hindrances to free diffusion, and the shape of a spectrum reveals the relative contributions of spatial restrictions at different distance scales. Such spectra differ from other so-called diffusion spectra which depict spatial frequencies and are defined at a fixed diffusion time. Experimentally, oscillating gradients at moderate frequency are more feasible for exploring restrictions at very short distances which, in Tissues, correspond to Structures smaller than cells. We describe the underlying concepts of temporal diffusion spectra and provide analytical expressions for the behavior of the diffusion coefficient as a function of gradient frequency in simple geometries with different dimensions. Diffusion in more complex model media that mimic Tissues has been simulated using numerical methods. Experimental measurements of diffusion spectra have been obtained in suspensions of particles and cells, as well as in vivo in intact animals. An observation of particular interest is the increased contrast and heterogeneity observed in tumors using oscillating gradients at moderate frequency compared with conventional pulse gradient methods, and the potential for detecting changes in tumors early in their response to treatment. Computer simulations suggest that diffusion spectral measurements may be sensitive to intracellular Structures, such as nuclear size, and that changes in Tissue diffusion properties may be measured before there are changes in cell density. Copyright © 2010 John Wiley & Sons, Ltd.
-
characterization of Tissue Structure at varying length scales using temporal diffusion spectroscopy
NMR in Biomedicine, 2010Co-Authors: John C Gore, Daniel C Colvin, Thomas E Yankeelov, Edward C Parsons, Mark D DoesAbstract:The concepts, theoretical behavior and experimental applications of temporal diffusion spectroscopy are reviewed and illustrated. Temporal diffusion spectra are obtained using oscillating-gradient waveforms in diffusion-weighted measurements, and represent the manner in which various spectral components of molecular velocity correlations vary in different geometrical Structures that restrict or hinder free movements. Measurements made at different gradient frequencies reveal information on the scale of restrictions or hindrances to free diffusion, and the shape of a spectrum reveals the relative contributions of spatial restrictions at different distance scales. Such spectra differ from other so-called diffusion spectra which depict spatial frequencies and are defined at a fixed diffusion time. Experimentally, oscillating gradients at moderate frequency are more feasible for exploring restrictions at very short distances which, in Tissues, correspond to Structures smaller than cells. We describe the underlying concepts of temporal diffusion spectra and provide analytical expressions for the behavior of the diffusion coefficient as a function of gradient frequency in simple geometries with different dimensions. Diffusion in more complex model media that mimic Tissues has been simulated using numerical methods. Experimental measurements of diffusion spectra have been obtained in suspensions of particles and cells, as well as in vivo in intact animals. An observation of particular interest is the increased contrast and heterogeneity observed in tumors using oscillating gradients at moderate frequency compared with conventional pulse gradient methods, and the potential for detecting changes in tumors early in their response to treatment. Computer simulations suggest that diffusion spectral measurements may be sensitive to intracellular Structures, such as nuclear size, and that changes in Tissue diffusion properties may be measured before there are changes in cell density.
Mina J Bissell - One of the best experts on this subject based on the ideXlab platform.
-
microenvironmental regulators of Tissue Structure and function also regulate tumor induction and progression the role of extracellular matrix and its degrading enzymes
Cold Spring Harbor Symposia on Quantitative Biology, 2005Co-Authors: Mina J Bissell, Paraic A Kenny, Derek C RadiskyAbstract:It is now widely accepted that elements of the cellular and Tissue microenvironment are crucial regulators of cell behavior in culture and homeostasis in vivo, and that many of the same factors influence the course of tumor progression. Less well established is the extent to which extracellular factors actually cause cancer, and the circumstances under which this may occur. Using physiologically relevant three-dimensional culture assays and transgenic animals, we have explored how the environmental and architectural context of cells, Tissues, and organs controls mammary-specific gene expression, growth regulation, apoptosis, and drug resistance and have found that loss of Tissue Structure is a prerequisite for cancer progression. Here we summarize this evidence and highlight two of our recent studies. Using mouse mammary epithelial cells, we show that exposure to matrix metalloproteinase-3 (MMP-3) stimulates production of reactive oxygen species (ROS) that destabilize the genome and induce epithelial-mesenchymal transition, causing malignant transformation. Using a human breast cancer progression series, we find that ADAM-dependent growth factor shedding plays a crucial role in acquisition of the malignant phenotype. These findings illustrate how normal Tissue Structure controls the response to extracellular signals so as to preserve Tissue specificity and growth status.
-
Tissue Structure nuclear organization and gene expression in normal and malignant breast
Cancer Research, 1999Co-Authors: Mina J Bissell, Valerie M Weaver, Sophie A Lelievre, Fei Wang, Ole W Petersen, Karen L SchmeichelAbstract:Abstract Because every cell within the body has the same genetic information, a significant problem in biology is to understand how cells within a Tissue express genes selectively. A sophisticated network of physical and biochemical signals converge in a highly orchestrated manner to bring about the exquisite regulation that governs gene expression in diverse Tissues. Thus, the ultimate decision of a cell to proliferate, express Tissue-specific genes, or apoptose must be a coordinated response to its adhesive, growth factor, and hormonal milieu. The unifying hypothesis examined in this overview is that the unit of function in higher organisms is neither the genome nor the cell alone but the complex, three-dimensional Tissue. This is because there are bidirectional connections between the components of the cellular microenvironment (growth factors, hormones, and extracellular matrix) and the nucleus. These connections are made via membrane-bound receptors and transmitted to the nucleus, where the signals result in modifications to the nuclear matrix and chromatin Structure and lead to selective gene expression. Thus, cells need to be studied “in context”, i.e., within a proper Tissue Structure, if one is to understand the bidirectional pathways that connect the cellular microenvironment and the genome. In the last decades, we have used well-characterized human and mouse mammary cell lines in “designer microenvironments” to create an appropriate context to study Tissue-specific gene expression. The use of a three-dimensional culture assay, developed with reconstituted basement membrane, has allowed us to distinguish normal and malignant human breast cells easily and rapidly. Whereas normal cells become growth arrested and form organized “acini,” tumor cells continue to grow, pile up, and in general fail to respond to extracellular matrix and microenvironmental cues. By correcting the extracellular matrix-receptor (integrin) signaling and balance, we have been able to revert the malignant phenotype when a human breast tumor cell is cultured in, or on, a basement membrane. Most recently, we have shown that whereas β1 integrin and epidermal growth factor receptor signal transduction pathways are integrated reciprocally in three-dimensional cultures, on Tissue culture plastic (two-dimensional monolayers), these are not coordinated. Finally, we have demonstrated that, rather than passively reflecting changes in gene expression, nuclear organization itself can modulate cellular and Tissue phenotype. We conclude that the Structure of the Tissue is dominant over the genome, and that we may need a new paradigm for how epithelial-specific genes are regulated in vivo. We also argue that unless the Structure of the Tissue is critically altered, malignancy will not progress, even in the presence of multiple chromosomal mutations.
-
Tissue architecture the ultimate regulator of epithelial function
Philosophical Transactions of the Royal Society B, 1998Co-Authors: Carmen Hagios, Andre Lochter, Mina J BissellAbstract:The architecture of a Tissue is defined by the nature and the integrity of its cellular and extracellular compartments, and is based on proper adhesive cell–cell and cell–extracellular matrix interactions. Cadherins and integrins are major adhesion–mediators that assemble epithelial cells together laterally and attach them basally to a subepithelial basement membrane, respectively. Because cell adhesion complexes are linked to the cytoskeleton and to the cellular signalling pathways, they represent checkpoints for regulation of cell shape and gene expression and thus are instructive for cell behaviour and function. This organization allows a reciprocal flow of mechanical and biochemical information between the cell and its microenvironment, and necessitates that cells actively maintain a state of homeostasis within a given Tissue context. The loss of the ability of tumour cells to establish correct adhesive interactions with their microenvironment results in disruption of Tissue architecture with often fatal consequences for the host organism. This review discusses the role of cell adhesion in the maintenance of Tissue Structure and analyses how Tissue Structure regulates epithelial function.
Laura Hindersin - One of the best experts on this subject based on the ideXlab platform.
-
should Tissue Structure suppress or amplify selection to minimize cancer risk
Biology Direct, 2016Co-Authors: Laura Hindersin, Benjamin Werner, David Dingli, Arne TraulsenAbstract:It has been frequently argued that Tissues evolved to suppress the accumulation of growth enhancing cancer inducing mutations. A prominent example is the hierarchical Structure of Tissues with high cell turnover, where a small number of Tissue specific stem cells produces a large number of specialized progeny during multiple differentiation steps. Another well known mechanism is the spatial organization of stem cell populations and it is thought that this organization suppresses fitness enhancing mutations. However, in small populations the suppression of advantageous mutations typically also implies an increased accumulation of deleterious mutations. Thus, it becomes an important question whether the suppression of potentially few advantageous mutations outweighs the combined effects of many deleterious mutations. We argue that the distribution of mutant fitness effects, e.g. the probability to hit a strong driver compared to many deleterious mutations, is crucial for the optimal organization of a cancer suppressing Tissue architecture and should be taken into account in arguments for the evolution of such Tissues. We show that for systems that are composed of few cells reflecting the typical organization of a stem cell niche, amplification or suppression of selection can arise from subtle changes in the architecture. Moreover, we discuss special Tissue Structures that can suppress most types of non-neutral mutations simultaneously. This article was reviewed by Benjamin Allen, Andreas Deutsch and Ignacio Rodriguez-Brenes. For the full reviews, please go to the Reviewers’ comments section.
-
should Tissue Structure suppress or amplify selection to minimize cancer risk
bioRxiv, 2016Co-Authors: Laura Hindersin, Benjamin Werner, David Dingli, Arne TraulsenAbstract:It has been frequently argued that Tissues evolved to suppress the accumulation of growth enhancing cancer inducing mutations. A prominent example is the hierarchical Structure of Tissues with high cell turnover, where a small number of Tissue specific stem cells produces a large number of specialised progeny during multiple differentiation steps. Another well known mechanism is the spatial organisation of stem cell populations and it is thought that this organisation suppresses fitness enhancing mutations. However, in small populations the suppression of advantageous mutations typically also implies an increased accumulation of deleterious mutations. Thus, it becomes an important question whether the suppression of potentially few advantageous mutations outweighs the combined effects of many deleterious mutations. We argue that the distribution of mutant fitness effects, e.g. the probability to hit a strong driver compared to many deleterious mutations, is crucial for the optimal organisation of a cancer suppressing Tissue architecture and should be taken into account in arguments for the evolution of such Tissues. We show that for systems that are composed of few cells reflecting the typical organisation of a stem cell niche, amplification or suppression of selection can arise from subtle changes in the architecture. Moreover, we discuss special Tissue Structures that can suppress most types of non-neutral mutations simultaneously.
