Journal of biomedical discovery and collaboration最新文献

What makes man human is his brain. This brain is obviously different from those of nonhuman primates. It is larger, shows hemispheric dominance and specialization, and is cytoarchitecturally somewhat more generalized. But are these the essential characteristics that determine the humanness of man? This paper cannot give an answer to this question for the answer is not known. But the problem can be stated more specifically, alternatives spelled out on the basis of available research results, and directions given for further inquiry. My theme will be that the human brain is so constructed that man, and only man, feels the thrust to make meaningful all his experiences and encounters. Development of this theme demands an analysis of the brain mechanisms that make meaning-and an attempt to define biologically the process of meaning. In this pursuit of meaning a fascinating variety of topics comes into focus: the coding and recoding operations of the brain; how it engenders and processes information and redundancy; and, how it makes possible signs and symbols and prepositional utterances. Of these, current research results indicate that only in the making of propositions is man unique-so here perhaps are to be found the keynotes that compose the theme.

Scientific and popular lore have promulgated a connection between emotion and the limbic forebrain. However, there are a variety of structures that are considered limbic, and disagreement as to what is meant by "emotion". This essay traces the initial studies upon which the connection between emotion and the limbic forebrain was based and how subsequent experimental evidence led to confusion both with regard to brain systems and to the behaviors examined. In the process of sorting out the bases of the confusion the following rough outlines are sketched: 1) Motivation and emotion need to be distinguished. 2) Motivation and emotion are processed by the basal ganglia; motivation by the striatum and related structures, emotion by limbic basal ganglia: the amygdala and related structures. 3) The striatum processes activation of readiness, both behavioral and perceptual; the amygdala processes arousal, an intensive dimension that varies from interest to panic. 4) Activation of readiness deals with "what to do?" Arousal deals with novelty, with "what is it?" 5) Thus both motivation and emotion are the proactive aspects of representations, of memory: motivation, an activation of readiness; emotion, a processing of novelty, a departure from the familiar. 6) The hippocampal-cingulate circuit deals with efficiently relating emotion and motivation by establishing dispositions, attitudes. 7) The prefrontal cortex fine-tunes motivation, emotion and attitude when choices among complex or ambiguous circumstances are made.

For a neurobiologist, the core of human nature is the human cerebral cortex, especially the prefrontal areas, and the question "what makes us human?" translates into studies of the development and evolution of the human cerebral cortex, a clear oversimplification. In this comment, after pointing out this oversimplification, I would like to show that it is impossible to understand our cerebral cortex if we focus too narrowly on it. Like other organs, our cortex evolved from that in stem amniotes, and it still bears marks of that ancestry. More comparative studies of brain development are clearly needed if we want to understand our brain in its historical context. Similarly, comparative genomics is a superb tool to help us understand evolution, but again, studies should not be limited to mammals or to comparisons between human and chimpanzee, and more resources should be invested in investigation of many vertebrate phyla. Finally, the most widely used rodent models for studies of cortical development are of obvious interest but they cannot be considered models of a "stem cortex" from which the human type evolved. It remains of paramount importance to study cortical development directly in other species, particularly in primate models, and, whenever ethically justifiable, in human.

Understanding how humans differ from other animals, as well as how we are like them, requires comparative investigations. For the purpose of documenting the distinctive features of humans, the most informative research involves comparing humans to our closest relatives-the chimpanzees and other great apes. Psychology and anthropology have maintained a tradition of empirical comparative research on human specializations of cognition. The neurosciences, by contrast, have been dominated by the model-animal research paradigm, which presupposes the commonality of "basic" features of brain organization across species and discourages serious treatment of species differences. As a result, the neurosciences have made little progress in understanding human brain specializations. Recent developments in neuroimaging, genomics, and other non-invasive techniques make it possible to directly compare humans and nonhuman species at levels of organization that were previously inaccessible, offering the hope of gaining a better understanding of the species-specific features of the human brain. This hope will be dashed, however, if chimpanzees and other great ape species become unavailable for even non-invasive research.

Unlabelled: The network model of innovation widely adopted among researchers in the economics of science and technology posits relatively porous boundaries between firms and academic research programs and a bi-directional flow of inventions, personnel, and tacit knowledge between sites of university and industry innovation. Moreover, the model suggests that these bi-directional flows should be considered as mutual stimulation of research and invention in both industry and academe, operating as a positive feedback loop. One side of this bi-directional flow--namely; the flow of inventions into industry through the licensing of university-based technologies--has been well studied; but the reverse phenomenon of the stimulation of university research through the absorption of new directions emanating from industry has yet to be investigated in much detail. We discuss the role of federal funding of academic research in the microarray field, and the multiple pathways through which federally supported development of commercial microarray technologies have transformed core academic research fields.

Results and conclusion: Our study confirms the picture put forward by several scholars that the open character of networked economies is what makes them truly innovative. In an open system innovations emerge from the network. The emergence and diffusion of microarray technologies we have traced here provides an excellent example of an open system of innovation in action. Whether they originated in a startup company environment that operated like a think-tank, such as Affymax, the research labs of a large firm, such as Agilent, or within a research university, the inventors we have followed drew heavily on knowledge resources from all parts of the network in bringing microarray platforms to light. Federal funding for high-tech startups and new industrial development was important at several phases in the early history of microarrays, and federal funding of academic researchers using microarrays was fundamental to transforming the research agendas of several fields within academe. The typical story told about the role of federal funding emphasizes the spillovers from federally funded academic research to industry. Our study shows that the knowledge spillovers worked both ways, with federal funding of non-university research providing the impetus for reshaping the research agendas of several academic fields.

Background: Knowledge bases that summarize the published literature provide useful online references for specific areas of systems-level biology that are not otherwise supported by large-scale databases. In the field of neuroanatomy, groups of small focused teams have constructed medium size knowledge bases to summarize the literature describing tract-tracing experiments in several species. Despite years of collation and curation, these databases only provide partial coverage of the available published literature. Given that the scientists reading these papers must all generate the interpretations that would normally be entered into such a system, we attempt here to provide general-purpose annotation tools to make it easy for members of the community to contribute to the task of data collation.

Results: In this paper, we describe an open-source, freely available knowledge management system called 'NeuroScholar' that allows straightforward structured markup of the PDF files according to a well-designed schema to capture the essential details of this class of experiment. Although, the example worked through in this paper is quite specific to neuroanatomical connectivity, the design is freely extensible and could conceivably be used to construct local knowledge bases for other experiment types. Knowledge representations of the experiment are also directly linked to the contributing textual fragments from the original research article. Through the use of this system, not only could members of the community contribute to the collation task, but input data can be gathered for automated approaches to permit knowledge acquisition through the use of Natural Language Processing (NLP).

Conclusion: We present a functional, working tool to permit users to populate knowledge bases for neuroanatomical connectivity data from the literature through the use of structured questionnaires. This system is open-source, fully functional and available for download from [1].

The Center for Behavioral Neuroscience was launched in the fall of 1999 with support from the National Science Foundation, the Georgia Research Alliance, and our eight participating institutions (Georgia State University, Emory University, Georgia Institute of Technology, Morehouse School of Medicine, Clark-Atlanta University, Spelman College, Morehouse College, Morris Brown College). The CBN provides the resources to foster innovative research in behavioral neuroscience, with a specific focus on the neurobiology of social behavior. Center faculty working in collaboratories use diverse model systems from invertebrates to humans to investigate fear, aggression, affiliation, and reproductive behaviors. The addition of new research foci in reward and reinforcement, memory and cognition, and sex differences has expanded the potential for collaborations among Center investigators. Technology core laboratories develop the molecular, cellular, systems, behavioral, and imaging tools essential for investigating how the brain influences complex social behavior and, in turn, how social experience influences brain function. In addition to scientific discovery, a major goal of the CBN is to train the next generation of behavioral neuroscientists and to increase the number of women and under-represented minorities in neuroscience. Educational programs are offered for K-12 students to spark an interest in science. Undergraduate and graduate initiatives encourage students to participate in interdisciplinary and inter-institutional programs, while postdoctoral programs provide a bridge between laboratories and allow the interdisciplinary research and educational ventures to flourish. Finally, the CBN is committed to knowledge transfer, partnering with community organizations to bring neuroscience to the public. This multifaceted approach through research, education, and knowledge transfer will have a major impact on how we study interactions between the brain and behavior, as well as how the public views brain function and neuroscience.

Introduction: Polymerase chain reaction (PCR) was a seminal genomic technology discovered, developed, and patented in an industry setting. Since the first of its core patents expired in March, 2005, we are in a position to view the entire lifespan of the patent, examining how the intellectual property rights have impacted its use in the biomedical community. Given its essential role in the world of molecular biology and its commercial success, the technology can serve as a case study for evaluating the effects of patenting biological research tools on biomedical research.

Case description: Following its discovery, the technique was subjected to two years of in-house development, during which issues of inventorship and publishing/patenting strategies caused friction between members of the development team. Some have feared that this delay impeded subsequent research and may have been due to trade secrecy or the desire for obtaining lucrative intellectual property rights. However, our analysis of the history indicates that the main reasons for the delay were benign and were primarily due to difficulties in perfecting the PCR technique. Following this initial development period, the technology was made widely available, but was subject to strict licensing terms and patent protection, leading to an extensive litigation history.

Discussion and evaluation: PCR has earned approximately $2 billion in royalties for the various rights-holders while also becoming an essential research tool. However, using citation trend analysis, we are able to see that PCR's patented status did not preclude it from being adopted in a similar manner as other non-patented genomic research tools (specifically, pBR322 cloning vector and Maxam-Gilbert sequencing).

Conclusion: Despite the heavy patent protection and rigid licensing schemes, PCR seems to have disseminated so widely because of the practices of the corporate entities which have controlled these patents, namely through the use of business partnerships and broad corporate licensing, adaptive licensing strategies, and a "rational forbearance" from suing researchers for patent infringement. While far from definitive, our analysis seems to suggest that, at least in the case of PCR, patenting of genomic research tools need not impede their dissemination, if the technology is made available through appropriate business practices.

Arrowsmith is a unique computer-assisted strategy designed to assist investigators in detecting biologically-relevant connections between two disparate sets of articles in Medline. This paper describes how an inter-institutional consortium of neuroscientists used the UIC Arrowsmith web interface http://arrowsmith.psych.uic.edu in their daily work and guided the development, refinement and expansion of the system into a suite of tools intended for use by the wider scientific community.