A Hybrid Model of Tumor–Stromal Interactions in Breast Cancer

Ductal carcinoma in situ (DCIS) is an early stage noninvasive breast cancer that originates in the epithelial lining of the milk ducts, but it can evolve into comedo DCIS and ultimately, into the most common type of breast cancer, invasive ductal carcinoma. Understanding the progression and how to effectively intervene in it presents a major scientific challenge. The extracellular matrix (ECM) surrounding a duct contains several types of cells and several types of growth factors that are known to individually affect tumor growth, but at present the complex biochemical and mechanical interactions of these stromal cells and growth factors with tumor cells is poorly understood. Here we develop a mathematical model that incorporates the cross-talk between stromal and tumor cells, which can predict how perturbations of the local biochemical and mechanical state influence tumor evolution. We focus on the EGF and TGF-β signaling pathways and show how up- or down-regulation of components in these pathways affects cell growth and proliferation. We then study a hybrid model for the interaction of cells with the tumor microenvironment (TME), in which epithelial cells (ECs) are modeled individually while the ECM is treated as a continuum, and show how these interactions affect the early development of tumors. Finally, we incorporate breakdown of the epithelium into the model and predict the early stages of tumor invasion into the stroma. Our results shed light on the interactions between growth factors, mechanical properties of the ECM, and feedback signaling loops between stromal and tumor cells, and suggest how epigenetic changes in transformed cells affect tumor progression.     

miR451 and AMPK mutual antagonism in glioma cell migration and proliferation: a mathematical model

Glioblastoma multiforme (GBM) is the most common and the most aggressive type of brain cancer; the median survival time from the time of diagnosis is approximately one year. GBM is characterized by the hallmarks of rapid proliferation and aggressive invasion. miR-451 is known to play a key role in glioblastoma by modulating the balance of active proliferation and invasion in response to metabolic stress in the microenvironment. The present paper develops a mathematical model of GBM evolution which focuses on the relative balance of growth and invasion. In the present work we represent the miR-451/AMPK pathway by a simple model and show how the effects of glucose on cells need to be "refined" by taking into account the recent history of glucose variations. The simulations show how variations in glucose significantly affect the level of miR-451 and, in turn, cell migration. The model predicts that oscillations in the levels of glucose increase the growth of the primary tumor. The model also suggests that drugs which upregulate miR-451, or block other components of the CAB39/AMPK pathway, will slow down glioma cell migration. The model provides an explanation for the growth-invasion cycling patterns of glioma cells in response to high/low glucose uptake in microenvironment in vitro, and suggests new targets for drugs, associated with miR-451 upregulation.     

中国外来陆生草本植物: 多样性和生态学特性

构建包含基本生物学和生态学信息的外来物种数据库不仅对理解生物入侵分布格局至关重要, 同时也是制定外来种管理策略和解释生物入侵过程的重要一步。作者在前人研究的基础上构建了中国外来陆生草本植物数据库, 共收集到中国外来陆生草本植物800种, 分属37目72科; 其中约有60%集中在菊科、豆科、仙人掌科、禾本科、十字花科等10个优势科。中国外来陆生草本植物主要来源于美洲(407种, 占总数的47%), 主要分布在南亚热带—热带区(46%, 密度为4种/10⁴km²), 其次为温带湿润区(26%, 密度约2种/10⁴km²)和亚热带区(23%, 密度约2种/10⁴km²), 旱—寒区(5%, 密度小于1种/10⁴km²)分布较少。从生活型上看, 以多年生 (293种, 40%)和一年生 (272种, 37%)为主; 而从生境类型来看, 约有一半(46%)分布于“高养分高干扰”类型的生境。约有80%的物种属有意引入, 因此有意引入是陆生外来草本植物进入中国的主要途径。近2个世纪来, 外来陆生草本植物进入中国的速度快速增加, 约90%的物种在这个时期进入; 而近半个世纪以来, 外来陆生草本植物进入中国的速度快速增长, 约60%的物种在这个时期进入中国。本文所提供的中国外来陆生草本植物的生物学和生态学特征, 可以为管理层制定外来种相关管理和控制策略提供参考信息。     

The role of the microenvironment in tumor growth and invasion

Mathematical modeling and computational analysis are essential for understanding the dynamics of the complex gene networks that control normal development and homeostasis, and can help to understand how circumvention of that control leads to abnormal outcomes such as cancer. Our objectives here are to discuss the different mechanisms by which the local biochemical and mechanical microenvironment, which is comprised of various signaling molecules, cell types and the extracellular matrix (ECM), affects the progression of potentially-cancerous cells, and to present new results on two aspects of these effects. We first deal with the major processes involved in the progression from a normal cell to a cancerous cell at a level accessible to a general scientific readership, and we then outline a number of mathematical and computational issues that arise in cancer modeling. In Section 2 we present results from a model that deals with the effects of the mechanical properties of the environment on tumor growth, and in Section 3 we report results from a model of the signaling pathways and the tumor microenvironment (TME), and how their interactions affect the development of breast cancer. The results emphasize anew the complexities of the interactions within the TME and their effect on tumor growth, and show that tumor progression is not solely determined by the presence of a clone of mutated immortal cells, but rather that it can be ‘community-controlled’.     

Effect of the food production chain from farm practices to vegetable processing on outbreak incidence

The popularity in the consumption of fresh and fresh-cut vegetables continues to increase globally. Fresh vegetables are an integral part of a healthy diet, providing vitamins, minerals, antioxidants and other health-promoting compounds. The diversity of fresh vegetables and packaging formats (spring mix in clamshell container, bagged heads of lettuce) support increased consumption. Unfortunately, vegetable production and processing practices are not sufficient to ensure complete microbial safety. This review highlights a few specific areas that require greater attention and research. Selected outbreaks are presented to emphasize the need for science-based ‘best practices’. Laboratory and field studies have focused on inactivation of pathogens associated with manure in liquid, slurry or solid forms. As production practices change, other forms and types of soil amendments are being used more prevalently. Information regarding the microbial safety of fish emulsion and pellet form of manure is limited. The topic of global climate change is controversial, but the potential effect on agriculture cannot be ignored. Changes in temperature, precipitation, humidity and wind can impact crops and the microorganisms that are associated with production environments. Climate change could potentially enhance the ability of pathogens to survive and persist in soil, water and crops, increasing human health risks. Limited research has focused on the prevalence and behaviour of viruses in pre and post-harvest environments and on vegetable commodities. Globally, viruses are a major cause of foodborne illnesses, but are seldom tested for in soil, soil amendments, manure and crops. Greater attention must also be given to the improvement in the microbial quality of seeds used in sprout production. Human pathogens associated with seeds can result in contamination of sprouts intended for human consumption, even when all appropriate ‘best practices’ are used by sprout growers.     

Choindroitinase ABC I-Mediated Enhancement of Oncolytic Virus Spread and Anti Tumor Efficacy: A Mathematical Model

Oncolytic viruses are genetically engineered viruses that are designed to kill cancer cells while doing minimal damage to normal healthy tissue. After being injected into a tumor, they infect cancer cells, multiply inside them, and when a cancer cell is killed they move on to spread and infect other cancer cells. Chondroitinase ABC (Chase-ABC) is a bacterial enzyme that can remove a major glioma ECM component, chondroitin sulfate glycosoamino glycans from proteoglycans without any deleterious effects in vivo. It has been shown that Chase-ABC treatment is able to promote the spread of the viruses, increasing the efficacy of the viral treatment. In this paper we develop a mathematical model to investigate the effect of the Chase-ABC on the treatment of glioma by oncolytic viruses (OV). We show that the model''s predictions agree with experimental results for a spherical glioma. We then use the model to test various treatment options in the heterogeneous microenvironment of the brain. The model predicts that separate injections of OV, one into the center of the tumor and another outside the tumor will result in better outcome than if the total injection is outside the tumor. In particular, the injection of the ECM-degrading enzyme (Chase-ABC) on the periphery of the main tumor core need to be administered in an optimal strategy in order to infect and eradicate the infiltrating glioma cells outside the tumor core in addition to proliferative cells in the bulk of tumor core. The model also predicts that the size of tumor satellites and distance between the primary tumor and multifocal/satellite lesions may be an important factor for the efficacy of the viral therapy with Chase treatment.     

广东石门台国家级自然保护区老虎山次生林群落特征

为了解在广东石门台国家级自然保护区的老虎山南坡建设的大型林冠模拟氮沉降野外控制试验平台的植被组成特征,开展了18个样方的每木调查和分析研究。结果表明,在面积0.72 hm²中有维管束植物53科86属127种;胸径(DBH)≥1.0 cm的立木有2 465株,平均密度为0.34 ind./m²,最高达25 m。群落以锥(Castanopsis chinensis)、罗伞树(Ardisia quinquegona)、木荷(Schima superba)等为主要优势种类,且以高位芽、中小型叶、革质和非全缘叶植物为主要种类组成的常绿阔叶次生林。热带-亚热带区系成分在群落中占明显优势,具有热带向亚热带过渡的特征。18个样方乔木层的Simpson指数(0.851～0.936)和Shannon-Wiener指数(3.504～4.494)相近,Pielou均匀度指数较高(0.780～1.000),但Gleason和Margalef丰富度指数差异较大(分别为3.209～7.738和16.760～40.806),样方间有10～26种共有种(Sorensen相似性...     

Physiological functions and Ca2+ signal transduction pathway exploring during molting of silkworm,Bombyx mori

Calcium ions are an important second messagers in the life of organisms, such as in silkworm growth and their developmental processes; these ions can trigger various effects, including the muscle excitation-contraction coupling mechanism, secretion of endocrine and exocrine glands, neuronal activities, midgut nutrients metabolisms, sensory system, enzymatic systems, and acceleration of metabolism activities. This paper reviewed the ecdysis process and mechanisms, where calcium plays an important role in larvae-to-larvae ecdysis and larvae-to-pupae and pupae-to-moth metamorphosis of silkworms; the paper focuses on the advanced achievements in the field of calcium actions during larvae-to-larvae and larvae-to-pupae changes. Calcium ion channels are shown to be the action mechanism of phospholipase C in the G protein cascade of the calcium signal transduction pathway, and the activators and inhibitors of these calcium channels are further discussed.     

Strategies of Eradicating Glioma Cells: A Multi-Scale Mathematical Model with MiR-451-AMPK-mTOR Control

The cellular dispersion and therapeutic control of glioblastoma, the most aggressive type of primary brain cancer, depends critically on the migration patterns after surgery and intracellular responses of the individual cancer cells in response to external biochemical and biomechanical cues in the microenvironment. Recent studies have shown that a particular microRNA, miR-451, regulates downstream molecules including AMPK and mTOR to determine the balance between rapid proliferation and invasion in response to metabolic stress in the harsh tumor microenvironment. Surgical removal of main tumor is inevitably followed by recurrence of the tumor due to inaccessibility of dispersed tumor cells in normal brain tissue. In order to address this multi-scale nature of glioblastoma proliferation and invasion and its response to conventional treatment, we propose a hybrid model of glioblastoma that analyses spatio-temporal dynamics at the cellular level, linking individual tumor cells with the macroscopic behaviour of cell organization and the microenvironment, and with the intracellular dynamics of miR-451-AMPK-mTOR signaling within a tumour cell. The model identifies a key mechanism underlying the molecular switches between proliferative phase and migratory phase in response to metabolic stress and biophysical interaction between cells in response to fluctuating glucose levels in the presence of blood vessels (BVs). The model predicts that cell migration, therefore efficacy of the treatment, not only depends on oxygen and glucose availability but also on the relative balance between random motility and strength of chemoattractants. Effective control of growing cells near BV sites in addition to relocalization of invisible migratory cells back to the resection site was suggested as a way of eradicating these migratory cells.