Why the stroma matters in breast cancer

Survival and recurrence rates in breast cancer are variable for common diagnoses, and therefore the biological underpinnings of the disease that determine those outcomes are yet to be fully understood. As a result, translational medicine is one of the fastest growing arenas of study in tumor biology. With advancements in genetic and imaging techniques, archived biopsies can be examined for purposes other than diagnosis. There is a great deal of evidence that points to the stroma as the major regulator of tumor progression following the initial stages of tumor formation, and the stroma may also contribute to risk factors determining tumor formation. Therefore, aspects of stromal biology are well-suited to be a focus for studies of patient outcome, where statistical differences in survival among patients provide evidence as to whether that stromal component is a signpost for tumor progression. In this review we summarize the latest research done where breast cancer patient survival was correlated with aspects of stromal biology, which have been put into four categories: reorganization of the extracellular matrix (ECM) to promote invasion, changes in the expression of stromal cell types, changes in stromal gene expression, and changes in cell biology signaling cascades to and from the stroma.     

Why the stroma matters in breast cancer: Insights into breast cancer patient outcomes through the examination of stromal biomarkers

Survival and recurrence rates in breast cancer are variable for common diagnoses, and therefore the biological underpinnings of the disease that determine those outcomes are yet to be fully understood. As a result, translational medicine is one of the fastest growing arenas of study in tumor biology. With advancements in genetic and imaging techniques, archived biopsies can be examined for purposes other than diagnosis. There is a great deal of evidence that points to the stroma as the major regulator of tumor progression following the initial stages of tumor formation, and the stroma may also contribute to risk factors determining tumor formation. Therefore, aspects of stromal biology are well-suited to be a focus for studies of patient outcome, where statistical differences in survival among patients provide evidence as to whether that stromal component is a signpost for tumor progression. In this review we summarize the latest research done where breast cancer patient survival was correlated with aspects of stromal biology, which have been put into four categories: reorganization of the extracellular matrix (ECM) to promote invasion, changes in the expression of stromal cell types, changes in stromal gene expression, and changes in cell biology signaling cascades to and from the stroma.     

Advances in Cell‐Free Biosensors: Principle,Mechanism, and Applications

Synthetic biology has promoted the development of biosensors as tools for detecting trace substances. In the past, biosensors based on synthetic biology have been designed on living cells, but the development of cell biosensors has been greatly limited by defects such as genetically modified organism problem and the obstruction of cell membrane. However, the advent of cell‐free synthetic biology addresses these limitations. Biosensors based on the cell‐free protein synthesis system have the advantages of higher safety, higher sensitivity, and faster response time over cell biosensors, which make cell‐free biosensors have a broader application prospect. This review summarizes the workflow of various cell‐free biosensors, including the identification of analytes and signal output. The detection range of cell‐free biosensors is greatly enlarged by different recognition mechanisms and output methods. In addition, the review also discusses the applications of cell‐free biosensors in environmental monitoring and health diagnosis, as well as existing deficiencies and aspects that should be improved. In the future, through continuous improvement and optimization, the potential of cell‐free biosensors will be stimulated, and their application fields will be expanded.     

Integrins and metastasis

Metastasis is a combination of biological events that makes the difference between cancer and other diseases. Metastasis requires flow of erroneous but precisely coordinated basic cellular activities like cell migration–invasion, cell survival–apoptosis, cell proliferation, etc. All of these processes require efficient regulation of cell attachment and detachment, which recruit integrin receptors in this flow of events. World literatures show several aspects of interrelation of integrins and metastasis. Integrin molecules are being used as prime target to battle metastasis. In this review we are collating the observations showing importance of integrin biology in regulation of metastasis and the strategies where integrin receptors are being used as targets to regulate metastasis.     

The state of the septin cytoskeleton from assembly to function

Septins are conserved guanine nucleotide-binding proteins that polymerize into filaments at the cell cortex or in association with other cytoskeletal proteins, such as actin or microtubules. As integral players in many morphogenic and signaling events, septins form scaffolds important for the recruitment of the cytokinetic machinery, organization of the plasma membrane, and orientation of cell polarity. Mutations in septins or their misregulation are associated with numerous diseases. Despite growing appreciation for the importance of septins in different aspects of cell biology and disease, septins remain relatively poorly understood compared with other cytoskeletal proteins. Here in this review, we highlight some of the recent developments of the last two years in the field of septin cell biology.     

Jamming and arrest of cell motion in biological tissues

Collective cell motility is crucial to many biological processes including morphogenesis, wound healing, and cancer invasion. Recently, the biology and biophysics communities have begun to use the term ‘cell jamming’ to describe the collective arrest of cell motion in tissues. Although this term is widely used, the underlying mechanisms are varied. In this review, we highlight three independent mechanisms that can potentially drive arrest of cell motion — crowding, tension-driven rigidity, and reduction of fluctuations — and propose a framework that connects all three. Because multiple mechanisms may be operating simultaneously, this emphasizes that experiments should strive to identify which mechanism dominates in a given situation. We also discuss how specific cell-scale and molecular-scale biological processes, such as cell–cell and cell-substrate interactions, control aspects of these underlying physical mechanisms.     

Nuclear and genome organization of Trypanosoma brucei

In this article, Klaus Ersfeld, Sara Melville and Keith Gull review current understanding of the structural organization of the nucleus of Trypanosoma brucei, and summarize recent data pertinent to the organization of its genome. Until recently, the cell biology of the trypanosome nucleus and issues of DNA organization and gene expression have often been treated as separate themes. However, recent work emphasizes the need for a more holistic approach to understanding these aspects of the biology of this parasite.     

Approaches to chemical synthetic biology

Synthetic biology is first represented in terms of two complementary aspects, the bio-engineering one, based on the genetic manipulation of extant microbial forms in order to obtain forms of life which do not exist in nature; and the chemical synthetic biology, an approach mostly based on chemical manipulation for the laboratory synthesis of biological structures that do not exist in nature. The paper is mostly devoted to shortly review chemical synthetic biology projects currently carried out in our laboratory. In particular, we describe: the minimal cell project, then the "Never Born Proteins" and lastly the Never Born RNAs. We describe and critically analyze the main results, emphasizing the possible relevance of chemical synthetic biology for the progress in basic science and biotechnology.     

Mitochondria in health and disease: perspectives on a new mitochondrial biology

The integrity of mitochondrial function is fundamental to cell life. It follows that disturbances of mitochondrial function will lead to disruption of cell function, expressed as disease or even death. In this review, I consider recent developments in our knowledge of basic aspects of mitochondrial biology as an essential step in developing our understanding of the contributions of mitochondria to disease. The identification of novel mechanisms that govern mitochondrial biogenesis and replication, and the delicately poised signalling pathways that coordinate the mitochondrial and nuclear genomes are discussed. As fluorescence imaging has made the study of mitochondrial function within cells accessible, the application of that technology to the exploration of mitochondrial bioenergetics is reviewed. Mitochondrial calcium uptake plays a major role in influencing cell signalling and in the regulation of mitochondrial function, while excessive mitochondrial calcium accumulation has been extensively implicated in disease. Mitochondria are major producers of free radical species, possibly also of nitric oxide, and are also major targets of oxidative damage. Mechanisms of mitochondrial radical generation, targets of oxidative injury and the potential role of uncoupling proteins as regulators of radical generation are discussed. The role of mitochondria in apoptotic and necrotic cell death is seminal and is briefly reviewed. This background leads to a discussion of ways in which these processes combine to cause illness in the neurodegenerative diseases and in cardiac reperfusion injury. The demands of mitochondria and their complex integration into cell biology extends far beyond the provision of ATP, prompting a radical change in our perception of mitochondria and placing these organelles centre stage in many aspects of cell biology and medicine.     

Epithelial topology

It is universally accepted that genetic control over basic aspects of cell and molecular biology is the primary organizing principle in development and homeostasis of living systems. However, instances do exist where important aspects of biological order arise without explicit genetic instruction, emerging instead from simple physical principles, stochastic processes, or the complex self-organizing interaction between random and seemingly unrelated parts. Being mostly resistant to direct genetic dissection, the analysis of such emergent processes falls into a grey area between mathematics, physics and molecular cell biology and therefore remains very poorly understood. We recently proposed a mathematical model predicting the emergence of a specific non-Gaussian distribution of polygonal cell shapes from the stochastic cell division process in epithelial cell sheets; this cell shape distribution appears to be conserved across a diverse set of animals and plants.1 The use of such topological models to study the process of cellular morphogenesis has a long history, starting almost a century ago, and many insights from those original works influence current experimental studies. Here we review current and past literature on this topic while exploring some new ideas on the origins and implications of topological order in proliferating epithelia.     

The viral killer system in yeast: from molecular biology to application

Since the initial discovery of the yeast killer system almost 40 years ago, intensive studies have substantially strengthened our knowledge in many areas of biology and provided deeper insights into basic aspects of eukaryotic cell biology as well as into virus-host cell interactions and general yeast virology. Analysis of killer toxin structure, synthesis and secretion has fostered understanding of essential cellular mechanisms such as post-translational prepro-protein processing in the secretory pathway. Furthermore, investigation of the receptor-mediated mode of toxin action proved to be an effective means for dissecting the molecular structure and in vivo assembly of yeast and fungal cell walls, providing important insights relevant to combating infections by human pathogenic yeasts. Besides their general importance in understanding eukaryotic cell biology, killer yeasts, killer toxins and killer viruses are also becoming increasingly interesting with respect to possible applications in biomedicine and gene technology. This review will try to address all these aspects.     

Immune-deficient mouse models for analysis of human stem cells

The field of murine models of xenotransplantation has grown immensely over the past two decades. The explosive growth in this field is in part due to the fact that good in vitro methods do not exist yet to allow examination of human stem cell homing into the bone marrow compartment versus other tissues, long-term survival of human stem cells, or differentiation into tissues outside of the hematopoietic system. Since these important aspects of human stem cell biology can be examined in vivo using immune-deficient mice, the number of different strains and models is constantly increasing. The current review discusses the merits and drawbacks of each immune-deficient mouse xenograft system as it stands to date and reviews how each immune-deficient mouse model has been used to further our knowledge of human hematopoietic stem cell biology.     

The application of atomic force microscopy to the study of living vertebrate cells in culture

Atomic force microscopy (AFM), a relatively new variant of scanning probe microscopy developed for the material sciences, is becoming an increasingly important tool in other disciplines. In this review I describe in nontechnical terms some of the basic aspects of using AFM to study living vertebrate cells. Although AFM has some unusual attributes such as an ability to be used with living cells, AFM also has attributes that make its use in cell biology a real challenge. This review was written to encourage researchers in the biological and biomedical sciences to consider AFM as a potential (and potent) tool for their cell biological research.     

Light Reaches the Very Heart of the Zebrafish Clock

Zebrafish are typically used as a model system to study various aspects of developmental biology, largely as a consequence of their ex vivo development, high degree of transparency, and, of course, ability to perform forward genetic mutant screens. More recently, zebrafish have been developed as a model system with which to study circadian clocks. Cell lines generated from early-stage zebrafish embryos contain clocks that are directly light-responsive. We describe recent experiments using single-cell luminescent imaging approaches to study clock function in this novel cell line system. Furthermore, studies examining the process of entrainment to light pulses within this cell population are described in this review, as are experiments examining light-responsiveness of early-stage zebrafish embryos.     

Biology and pathogenesis of Fonsecaea pedrosoi, the major etiologic agent of chromoblastomycosis

Fonsecaea pedrosoi is the principal etiologic agent of chromoblastomycosis, a fungal disease whose pathogenic events are poorly understood. Treatment of the disease presents poor effectiveness and serious side effects. The disease is epidemiologically important in several regions, which has stimulated studies focused on the biology and pathogenic potential of its major causative agent. In this review, we summarize the current knowledge on the biological aspects of F. pedrosoi, including cell differentiation and pathogenic mechanisms during the interaction of fungi with different hosts' elements.     

Light reaches the very heart of the zebrafish clock

Zebrafish are typically used as a model system to study various aspects of developmental biology, largely as a consequence of their ex vivo development, high degree of transparency, and, of course, ability to perform forward genetic mutant screens. More recently, zebrafish have been developed as a model system with which to study circadian clocks. Cell lines generated from early-stage zebrafish embryos contain clocks that are directly light-responsive. We describe recent experiments using single-cell luminescent imaging approaches to study clock function in this novel cell line system. Furthermore, studies examining the process of entrainment to light pulses within this cell population are described in this review, as are experiments examining light-responsiveness of early-stage zebrafish embryos.