The Novartis-ILAR Rheumatology Prize 2001 Osteoarthritis: from molecule to man

During our careers, we have developed new and innovative concepts pertaining to the pathophysiology of osteoarthritis which have assisted in the development of new therapeutic approaches. Moreover, our laboratory has long sought to develop protective agents for osteoarthritic structural joint tissues. The most significant concepts that have originated from our lab are briefly outlined in this commentary.     

Sequence census methods for functional genomics

Next-generation sequencing technologies are beginning to facilitate genome sequencing. But in addition, new applications and new assay concepts have emerged that are vastly increasing our ability to understand genome function.     

GLIA: A reassessment based on novel data on the developing and mature central nervous system

Several studies on neurobiology have contributed to our understanding of the genesis, survival and death of neurons, unquestionably the stars of the Central Nervous System (CNS). However, they would not be so famous without their close associates: the glial cells. Since novel studies have demonstrated new and important functions for glial cells, they are beginning to gain significant importance in brain research to allow us to reinterpret long known functions on the basis of new concepts. Here, we review recent progress in our understanding of the role of glial cells in the biology of tissue development and maturation.     

The Green Design Apprenticeship

In order to convey the results of our industrial ecology research to broader audiences, the Green Design Institute research group at Carnegie Mellon University offers the Green Design Apprenticeship for local high school students. The Green Design Apprenticeship introduces participants to industrial ecology concepts and how they intersect with engineering. The content of the program has evolved to include the topics of life cycle assessment, energy and water resources, transportation, and the built environment. The program has resulted in exposing a new generation of scholars to industrial ecology and has also benefited the research of graduate students involved with the program. The process of developing the instructional materials for younger, novice students based on complex industrial ecology research was a challenging task requiring thoughtful and iterative planning. Through the development and delivery of the program, we have experienced awareness of where our own research fits into the larger industrial ecology scope, have improved our communication of complex industrial ecology concepts into simple terms, and have gained valuable insight for engaging students in our teaching.     

Homophilic adhesion by cadherins.

Cadherins mediate cell-cell adhesion through homophilic interactions. High-resolution structures have greatly enhanced our understanding of this phenomenon over the past few years. Nonetheless, some of the original concepts about cadherin interactions need revision, with the new structural and additional mutagenesis data currently available. Furthermore, in vivo studies on cadherins have provided supplementary information.     

Intra-Golgi transport: a way to a new paradigm?

The morpho-functional principles of intra-Golgi transport are, surprisingly, still not clear, which is in marked contrast to our advanced knowledge of the underlying molecular machineries. Recently, the conceptual and technological hindrances that had delayed progress in this area have been disappearing, and a cluster of powerful morphological techniques has been revealing new glimpses of the organization of traffic in intact cells. Here, we discuss the new concepts around the present models of intra-Golgi transport.     

Genomic instability, bystander effects and radiation risks: implications for development of protection strategies for man and the environment

The last few years has seen what people are now referring to as a "shifting Paradigm" in our way of thinking about radiation effects on biological systems. The concept of the central role of DNA damage due to double strand breaks induced by a radiation "hit" has been itself hit by many studies showing persistent effects in the distant progeny of radiation exposed cells. This phenomenon is known as radiation induced genomic instability. More recently evidence has been accumulating that not even the parent cell need be exposed to radiation (the bystander effect). The new paradigm suggests that cellular stress responses or damage signalling through a range of signal transduction pathways are involved and that cell-cell contact or secretion of damage signalling molecules can induce responses in undamaged and unirradiated cells. Are these new effects relevant to risk assessment, or does it matter HOW radiation affects cells if we have good epidemiological evidence of which to base our risk estimates? The aim of this paper is to introduce the new concepts and to consider reasons why they might alter our methods of risk estimation. The paper also considers the impact of the new concepts on environmental protection and discusses the need for research in the field of comparative radiobiology if we are to develop policies which can adequately protect biodiversity.     

Imaging techniques for assaying lymphocyte activation in action

Imaging techniques have greatly improved our understanding of lymphocyte activation. Technical advances in spatial and temporal resolution and new labelling tools have enabled researchers to directly observe the activation process. Consequently, research using imaging approaches to study lymphocyte activation has expanded, providing an unprecedented level of cellular and molecular detail in the field. As a result, certain models of lymphocyte activation have been verified, others have been revised and yet others have been replaced with new concepts. In this article, we review the current imaging techniques that are used to assess lymphocyte activation in different contexts, from whole animals to single molecules, and discuss the advantages and potential limitations of these methods.     

Mitochondrial encephalomyopathies: Clinical and molecular analysis

The classification of mitochondrial encephalomyopathies relied upon clinical, biochemical, and histological features until the discovery of mitochondrial DNA defects in 1988. Since then, an outburst of molecular genetic information has aided our understanding of the pathogenesis and the classification of these heterogeneous disorders. Novel concepts of maternal inheritance, mitochondrial DNA (mtDNA) heteroplasmy, tissue distribution, and threshold have explained many of the clinical characteristics. The discovery of point mutations, large-scale mtDNA deletions, duplications, and autosomally inherited disorders with multiple mtDNA deletions have revealed new genetic phenomena. Despite our rapidly expanding understanding of the molecular genetic defects, many questions remain to be explored to fill the gap in our knowledge of the relationship between genotype and clinical phenotype.     

人工林碳汇潜力新概念及应用

定量确定森林碳汇潜力有助于科学地评估森林对碳汇的潜在贡献及制定实现这种潜力所需要的经营管理措施。目前,国内外有关森林碳汇潜力缺乏统一的概念及计量方法。在综述国内外有关固碳潜力概念的基础上,引入时间动态构架和可持续性的概念,提出了针对人工林的固碳潜力概念并利用FORECAST模型以杉木人工林为例阐明此概念的实际意义与应用。     

Marine eutrophication and benthos: the need for new approaches and concepts

In this review, using examples drawn from field observations or experimental studies, our goals are (i) to briefly summarize the major changes, in terms of species composition and functional structure, occurring in phyto and zoobenthic communities in relation to nutrient enrichment of the ecosystems; particular interest is given to the major abiotic and biotic factors occurring during the eutrophication process, (ii) to discuss the direct and indirect influences of benthic organisms on eutrophication and whether the latter can be controlled or favoured by benthos; most benthic species play a major role in the process of benthic nutrient regeneration, affecting primary production by supplying nutrients directly and enhancing rates of pelagic recycling; experimental studies have shown that the impact of benthic fauna on benthic–pelagic coupling and nutrient release is considerable. Thus, once the eutrophication process is engaged—that is, high organic matter sedimentation—it may be indirectly favoured by benthic organisms; benthos should always be considered in eutrophication studies, (iii) to evaluate the limits of our observations and data, highlighting the strong need for integrated studies leading to new concepts. Coastal ecosystems and benthic communities are potentially impacted by numerous human activities (demersal fishing, toxic contaminants, aquaculture…); in order to design strategies of ecosystem restoration or rehabilitation, we have to better understand coastal eutrophication and develop tools for quantifying the impacts; in order to achieve this goal, some possible directions proposed are: integrated studies leading to new concepts, model development based on these concepts and finally comparison of various ecosystems on a global scale.     

A 21st century view of evolution: genome system architecture, repetitive DNA, and natural genetic engineering

The last 50 years of molecular genetics have produced an abundance of new discoveries and data that make it useful to revisit some basic concepts and assumptions in our thinking about genomes and evolution. Chief among these observations are the complex modularity of genome organization, the biological ubiquity of mobile and repetitive DNA sequences, and the fundamental importance of DNA rearrangements in the evolution of sequenced genomes. This review will take a broad overview of these developments and suggest some new ways of thinking about genomes as sophisticated informatic storage systems and about evolution as a systems engineering process.     

Host-vector systems

In 1980 it was only possible to express foreign genes in bacteria and a few easily cultured animal cells. During the subsequent eight years specialized vectors have been developed to allow the genetic manipulation of a wide range of both prokaryotes and eukaryotes. One of the major goals of biotechnology in 1980 was to use host cells as 'factories' for the production of proteins that were only available in minute quantities from natural sources. This has already lead to a new generation of pharmaceutical products. Advances in our understanding of host-vector systems have defined new goals. The basic concepts of expression vector design will be illustrated. Some of the new goals are discussed with particular reference to the exploitation of novel host-vector systems to develop vaccines and anti-viral agents against AIDS.     

Gene therapy for peripheral arterial disease

Our understanding of the molecular biology of vascular disease is rapidly expanding, and this scientific growth has brought with it new opportunities for therapeutic intervention at the molecular and genetic levels. Although our tools for genetic manipulation in vivo and our knowledge of potential molecular targets are still crude and incomplete, the early application of these concepts to clinical problems is already underway, both in the pre-clinical and clinical arenas. The treatment of peripheral vascular disease, although greatly improved over recent decades by surgical and minimally-invasive techniques, remains limited by vascular proliferative lesions and by our inability to modulate the progression of native disease. This review explores some of the evolving concepts of therapeutic gene manipulation and their initial application in the peripheral circulation.     

Life With or Without Names

The terms ‘life’, ‘species’ and ‘individuals’ are key concepts in biology. However, theoretical and practical concerns are directly associated with definitions of these terms and their use in researchers’ work. Although the practical implications of employing definition of ‘species’ and ‘individuals’ are often clear, it is surprising how most biologists work in their field of study without adhering to a specific definition of life. In everyday scientific practice, biologists rarely define life. This is somewhat understandable: the majority of biologists accept the standard definition of life without exploring it, but this represents a bad attitude. In this essay, we update the concepts of life, species, and individuals in the light of the new techniques for massive DNA sequencing collectively known as high throughput DNA sequencing (HTS). A re-evaluation of the newest approaches and traditional concepts is required, because in many scientific publications, HTS users apply concepts ambiguously (in particular that of species). However, the absence of clarity is understandable. For most of the last 250 years, from Linnaeus to the most recent researches, identification and classification have been performed applying the same process. On the contrary, through HTS, biologists have become simply identifiers, who construct boundaries around the biological entities and do not examine the taxa at length, resulting in uncertainty in most readers and displeasure in traditional taxonomists. We organised our essay to answer a basic question: can we develop new means to observe living organisms?     

Fluctuation-driven flocking movement in three dimensions and scale-free correlation

Recent advances in the study of flocking behavior have permitted more sophisticated analyses than previously possible. The concepts of "topological distances" and "scale-free correlations" are important developments that have contributed to this improvement. These concepts require us to reconsider the notion of a neighborhood when applied to theoretical models. Previous work has assumed that individuals interact with neighbors within a certain radius (called the "metric distance"). However, other work has shown that, assuming topological interactions, starlings interact on average with the six or seven nearest neighbors within a flock. Accounting for this observation, we previously proposed a metric-topological interaction model in two dimensions. The goal of our model was to unite these two interaction components, the metric distance and the topological distance, into one rule. In our previous study, we demonstrated that the metric-topological interaction model could explain a real bird flocking phenomenon called scale-free correlation, which was first reported by Cavagna et al. In this study, we extended our model to three dimensions while also accounting for variations in speed. This three-dimensional metric-topological interaction model displayed scale-free correlation for velocity and orientation. Finally, we introduced an additional new feature of the model, namely, that a flock can store and release its fluctuations.     

Changing concepts of the pulmonary plexiform lesion

The plexiform lesion is the hallmark of plexogenic pulmonary arteriopathy, which accompanies severe primary pulmonary hypertension. Over the years, a wide variety of hypotheses have been offered to explain the pathogenesis of these glomoid structures. Most recently, the new techniques and concepts of molecular biology have been applied to the study of the plexiform lesion and have indicated that they are composed of phenotypically abnormal endothelial cells with different pathogenic origins in primary and secondary pulmonary hypertension. The new approaches and concepts have suggested new vistas for exploration.     

A hierarchical biology concept framework: a tool for course design

A typical undergraduate biology curriculum covers a very large number of concepts and details. We describe the development of a Biology Concept Framework (BCF) as a possible way to organize this material to enhance teaching and learning. Our BCF is hierarchical, places details in context, nests related concepts, and articulates concepts that are inherently obvious to experts but often difficult for novices to grasp. Our BCF is also cross-referenced, highlighting interconnections between concepts. We have found our BCF to be a versatile tool for design, evaluation, and revision of course goals and materials. There has been a call for creating Biology Concept Inventories, multiple-choice exams that test important biology concepts, analogous to those in physics, astronomy, and chemistry. We argue that the community of researchers and educators must first reach consensus about not only what concepts are important to test, but also how the concepts should be organized and how that organization might influence teaching and learning. We think that our BCF can serve as a catalyst for community-wide discussion on organizing the vast number of concepts in biology, as a model for others to formulate their own BCFs and as a contribution toward the creation of a comprehensive BCF.     

Schistosomes: the road from host-parasite interactions to vaccines in clinical trials

Insights over recent years into the interactions between helminths, including schistosomes, and the immune system have generated new concepts in immunology and significant advances in vaccine strategies. Here, we report recent advances that substantially increase our understanding of the nature of the host innate and adaptive responses to schistosomes and on strategies elaborated by the parasite to manipulate such responses. We also describe the long road that has allowed us to move from the identification of an anti-schistosome vaccine candidate, a 28kDa glutathione-S-transferase, to its recent evaluation in human clinical trials.