Transgenic rabbit models for biomedical research: Current status, basic methods and future perspectives

The creation of genetically modified laboratory and livestock animals is one of the most dramatic advances derived from recombinant DNA technology. Over the past decade, the development of a large mammal transgenic model, transgenic rabbits, has provided unprecedented opportunities for investigators to study the mechanisms of human diseases and has also provided a novel way to produce foreign proteins for both therapeutic and commercial purposes. Recent progress in gene targeting and animal cloning has opened new avenues for production of transgenic rabbits. In this review, we will introduce the reader to the progress that has been achieved in transgenic rabbits with emphasis on the application of these rabbits as human disease models and bioproducers of human therapeutic proteins.     

Incorporating collaboratory concepts into informatics in support of translational interdisciplinary biomedical research

Due to its complex nature, modern biomedical research has become increasingly interdisciplinary and collaborative in nature. Although a necessity, interdisciplinary biomedical collaboration is difficult. There is, however, a growing body of literature on the study and fostering of collaboration in fields such as computer supported cooperative work (CSCW) and information science (IS). These studies of collaboration provide insight into how to potentially alleviate the difficulties of interdisciplinary collaborative research. We, therefore, undertook a cross cutting study of science and engineering collaboratories to identify emergent themes. We review many relevant collaboratory concepts: (a) general collaboratory concepts across many domains: communication, common workspace and coordination, and data sharing and management, (b) specific collaboratory concepts of particular biomedical relevance: data integration and analysis, security structure, metadata and data provenance, and interoperability and data standards, (c) environmental factors that support collaboratories: administrative and management structure, technical support, and available funding as critical environmental factors, and (d) future considerations for biomedical collaboration: appropriate training and long-term planning. In our opinion, the collaboratory concepts we discuss can guide planning and design of future collaborative infrastructure by biomedical informatics researchers to alleviate some of the difficulties of interdisciplinary biomedical collaboration.     

椎间盘退变动物模型的研究现状与进展

椎间盘退行性疾病（intervertebral disc degenerative diseases, IDDDs）是跟衰老相关的典型脊柱疾病,是造成下腰痛的主要原因,严重影响着患者的劳动能力和生活质量。关于IDDDs的发病机制目前尚不完全清楚,因而建立椎间盘退变的实验动物模型对于IDDDs的发生机制和临床前研究具有不可替代的作用。利用实验动物从不同方法诱发其椎间盘退变,可以部分模拟人类的椎间盘退变这一复杂的生理、病理过程,并以此探究椎间盘退行性疾病的病理发展过程和药物治疗手段。本文总结了当前常用的椎间盘退行性疾病的实验动物模型,并且对比不同动物模型的优缺点、适用性及局限性,建议实验者可以根据实验对象、实验时间、病理要求等条件,选定最适合其研究的椎间盘退变的动物模型。     

Crossing the bridge: large animal models in translational transplantation research

Summary:  Many methods for reducing the immunosuppressive requirements of allotransplantation have been proposed based on a growing understanding of physiological and allospecific immunity. As these regimens are developed for clinical application, they require validation in models that are reasonably predictive of their performance in humans. This article provides an overview of the large animal models commonly used to test immunomodulatory organ transplant protocols. The rationale for the use of large animals and the effects of common immunosuppressants in the dog, pig, and non-human primate are reviewed. Promising methods for the induction of allospecific tolerance are surveyed with references to early human trials where appropriate.     

Defining success for translational research organizations

Translational research organizations (TROs) seek to enhance the clinical impact of scientific discoveries and play a multifaceted role characterized by multidisciplinary collaboration, outreach initiatives, and the provision of shared resources and facilities. Given this complexity, TROs require a flexible framework for performance assessment that tracks their progress, incentivizes fruitful activities, and aligns individuals throughout the organization. We suggest a framework that assesses TRO performance along seven main dimensions-funding, talent, creation, validation, dissemination, external uptake, and collaboration-and we encourage individual organizations to develop additional metrics as needed.     

Electron cryomicroscopy as a powerful tool in biomedical research

A human cell is a precisely regulated system that relies on the complex interaction of molecules. Structural insights into the cellular machinery at the atomic level allow us to understand the underlying regulatory mechanism and provide us with a roadmap for the development of novel drugs to fight diseases. Facilitated by recent technological breakthroughs, the Nobel prize-winning technique electron cryomicroscopy (cryo-EM) has become a versatile and extremely powerful tool to solve routinely near-atomic resolution three-dimensional protein structures. Consequently, it has become the focus of attention for structure-based drug design. In this review, we describe the basics of cryo-EM and highlight its growing role in biomedical research. Furthermore, we discuss latest developments as well as future perspectives.     

A classification for biomedical research reports

Biomedical research uses a wide range of designs applied to problems in laboratory, clinical, and population settings. Whatever the nature of the study, a few key features--such as the admission rule, the method of allocating subjects to treatments, and the use of controls--largely determine the strength of scientific inferences. We used these and other features to classify the 332 Original Articles published in the New England Journal of Medicine during 1978-1979. This classification directs attention to critical aspects of study design and performance and can help in the choice of suitable research approaches and protocols. It emphasizes the critical role of the investigators' intent in performing and analyzing a study, and it alerts readers to important aspects of interpretation. We recommend that authors always report enough detail about their work for readers to apply this or a similar classification. Omission of such detail may limit the interpretation of a research study because a study that cannot be classified has probably been incompletely reported.     

Small laboratory fish as models for aging research

Fish represent approximately half of all vertebrate species, yet have received little attention as models for aging research relative to invertebrate organisms or rodents. However, the basic gerontological characteristics of several fish species have been studied and provide compelling data for further investigation. In particular, guppies have proved to be an invaluable model for evolutionary analyses of aging, killifish are short-lived and may be exploitable for life span manipulation studies, and zebrafish come with a formidable armament of associated biological tools from their widespread use as a model of vertebrate development. These fish are well suited for the investigation of basic processes implicated in aging, such as insulin signaling, oxidative stress, and comparative studies of species with widely divergent longevities. Under-explored areas for which these fish may also provide unique research opportunities include their use as platforms for disease modeling, drug discovery, and regenerative medicine.     

An automated reasoning framework for translational research

In this paper we propose a novel approach to the design and implementation of knowledge-based decision support systems for translational research, specifically tailored to the analysis and interpretation of data from high-throughput experiments. Our approach is based on a general epistemological model of the scientific discovery process that provides a well-founded framework for integrating experimental data with preexisting knowledge and with automated inference tools.In order to demonstrate the usefulness and power of the proposed framework, we present its application to Genome-Wide Association Studies, and we use it to reproduce a portion of the initial analysis performed on the well-known WTCCC dataset. Finally, we describe a computational system we are developing, aimed at assisting translational research. The system, based on the proposed model, will be able to automatically plan and perform knowledge discovery steps, to keep track of the inferences performed, and to explain the obtained results.     

Advancing translational research collaborations

In February 2010, the U.S. National Institutes of Health (NIH) sponsored a national Clinical and Translational Science Awards forum titled "Promoting Efficient and Effective Collaborations among Academia, Government and Industry." This forum brought together a broad set of stakeholders who were charged with developing a path for promoting such partnerships. Here, we describe key issues discussed at the forum and plans for moving forward with this ambitious agenda.     

Transgenic animal models for virus-induced autoimmune diseases

In the pathogenesis of autoimmune diseases, tolerance against self-determinants is lost and autoreactive lymphocytes are activated leading to pathological damage of single or multiple organs. Viral and other microbial infections have been implicated in these processes. Viruses may induce immunopathological damage by maintaining a chronic immune response against the locally persisting infectious agent. Alternatively, viruses may help to initiate anti-self immunoreactivity, e.g. by induction of an inflammatory milieu needed to overcome tolerance against self-antigens. Presentation of viral antigens and/or previously immunologically ignored self-antigens in secondary lymphoid organs is most probably the key event in the initiation of autoimmune diseases. Translocation of antigens to secondary lymphoid organs and primary induction of T cell responses is primarily mediated by dendritic cells (DCs). We discuss here two transgenic models of autoimmune diseases where DC-mediated antigen transport initiated autoimmune responses against microbial neoself antigens. In the first model, dose and timing of antigen delivery by DCs and turnover of antigenic peptides presented by DCs are the main parameters regulating the outcome of autoimmune diabetes. In the second model, chronic stimulation of organ-specific immune responses via DCs leads to severe cardiovascular immunopathology with arteritis, myocarditis and eventually dilated cardiomyopathy. Taken together, transgenic mouse models are valuable tools for delineating basic pathogenic mechanisms and evaluating therapeutic strategies to interfere with early detrimental processes that lead to manifest autoimmune diseases.