Rem sleep without atonia--from cats to humans

Basic science research observations often lead to unexpected surprises. It is likely that in 1965 when Dr. Michel Jouvet placed bilateral peri-locus coeruleus lesions in cats and observed REM sleep without atonia (RWA) and "oneiric" behavior that could only be explained by "acting out dreams" (or "dreaming out acts"), he recognized that it was an important observation, but had little inkling of its true significance. Nor could he even imagine that it would lead to such greater understanding of wake/sleep phenomena in humans. Likely also, the first observation of REM sleep behavior disorder (RBD) in humans was felt to be interesting and novel - again with no true appreciation of what this seemingly simple observation would lead to important clinical relationships with numerous neurodegenerative disorders. The identification of RBD in humans also buttressed the concept of state dissociation, which has served to explain many previously unexplainable human behavioral phenomena.     

Autistic spectrum disorder: diagnostic difficulties

Recognition of the autistic spectrum disorders is becoming more widespread amongst basic scientists, clinicians, and the general population. The term does not imply anything about pathology or aetiology, although it has proved to be a useful concept clinically. From Kanner's classical autism the concept has widened in scope to include milder and more subtle impairments. From a clinical perspective, there are many alternative diagnoses in an individual with autistic-like symptoms, and thorough investigation is necessary to exclude these.     

Science Educational Outreach Programs That Benefit Students and Scientists

Both scientists and the public would benefit from improved communication of basic scientific research and from integrating scientists into education outreach, but opportunities to support these efforts are limited. We have developed two low-cost programs—"Present Your PhD Thesis to a 12-Year-Old" and "Shadow a Scientist”—that combine training in science communication with outreach to area middle schools. We assessed the outcomes of these programs and found a 2-fold benefit: scientists improve their communication skills by explaining basic science research to a general audience, and students'' enthusiasm for science and their scientific knowledge are increased. Here we present details about both programs, along with our assessment of them, and discuss the feasibility of exporting these programs to other universities.     

Psychiatric endophenotypes and the development of valid animal models

Endophenotypes are quantifiable components in the genes-to-behaviors pathways, distinct from psychiatric symptoms, which make genetic and biological studies of etiologies for disease categories more manageable. The endophenotype concept has emerged as a strategic tool in neuropsychiatric research. This emergence is due to many factors, including the modest reproducibility of results from studies directed toward etiologies and appreciation for the complex relationships between genes and behavior. Disease heterogeneity is often guaranteed, rather than simplified, through the current diagnostic system; inherent benefits of endophenotypes include more specific disease concepts and process definitions. Endophenotypes can be neurophysiological, biochemical, endocrine, neuroanatomical, cognitive or neuropsychological. Heritability and stability (state independence) represent key components of any useful endophenotype. Importantly, they characterize an approach that reduces the complexity of symptoms and multifaceted behaviors, resulting in units of analysis that are more amenable to being modeled in animals. We discuss the benefits of more direct interpretation of clinical endophenotypes by basic behavioral scientists. With the advent of important findings regarding the genes that predispose to psychiatric illness, we are at an important crossroads where, without anthropomorphizing, animal models may provide homologous components of psychiatric illness, rather than simply equating to similar (loosely analogized) behaviors, validators of the efficacy of current medications or models of symptoms. We conclude that there exists a need for increased collaboration between clinicians and basic scientists, the result of which should be to improve diagnosis, classification and treatment on one end and to increase the construct relevance of model organisms on the other.     

Doctor in the lab: what is it like for a doctor to work with scientists?

As clinical academic medical departments strive to improve the quality of their research, clinicians and scientists are forced into closer liaison. In many cases, clinical departments now have research laboratories directed by "basic scientists" but often staffed, in part at least, by doctors. To someone who has not worked in one, these laboratories may seem uncompromising and forbidding work environments. This article presents a "case report" written from the viewpoints of the doctor, the scientist, and the professor.     

Cancer therapies: basic and clinical perspectives in brain, prostate, and lung tumors: Naples, September, 24-27, 2000.

A continuous flow of theoretical and practical information among basic research, diagnosis, and therapeutic innovation is a crucial process to achieve a timely and effective progress in defeating human cancer. According to this essential concept, the main objective of the Fourth Joint International Cancer Conference "Cancer Therapies: Basic and Clinical Perspectives in Brain, Prostate and Lung Cancer" has been of gathering together basic scientists and clinicians who represent scientific opinion leaders in their field, to present and discuss the most recent scientific achievements in basic and clinical perspectives, advanced diagnostic and therapeutic strategies, and molecular and cellular therapeutic approaches in brain, prostate, and lung cancer.     

Prevalence of GB virus type C in urban Americans infected with human immunodeficiency virus type 1

Human T-lymphotropic virus type 1 (HTLV-1) and HTLV-2 were among the first human retroviruses discovered in the early 1980's. The International Retrovirology Association is an organized effort that fostered the efforts of scientists and clinicians to form interdisciplinary groups to study this group of retroviruses and their related diseases. The Association promotes excellent science, patient education, and fosters the training of young scientists to promote "bench-to-bedside" research. The International Conference on Human Retrovirology: HTLV and Related Viruses sponsored by the Association supports clinicians and researchers in the exchange of research findings and stimulation of new research directions. This years conference will be held from June 22 to 25, in Montego Bay, Jamaica http://www.htlvconference.org.jm/. Since its inception in 1988, these conferences have provided a highly interactive forum for the global community of HTLV scientists. This is of particular importance as HTLV research enters its third decade and a new generation of scientists takes over this important work. Many of the scientists attending the meeting will be from developing countries where HTLV is endemic, consistent with the history of international collaborations that have characterized HTLV research. The International Conference on Human Retrovirology provides a unique opportunity for researchers of all disciplines interested in HTLV infections to meet their peers and to address the questions facing clinicians and scientists who study retroviruses, like HTLV.     

Interface Biology of Implants

Implants are widely used in various clinical disciplines to replace or stabilize organs. The challenge for the future is to apply implant materials to specifically control the biology of the surrounding tissue for repair and regeneration. This field of research is highly interdisciplinary and combines scientists from technical and life sciences disciplines. To successfully apply materials for regenerative processes in the body, the understanding of the mechanisms at the interface between cells or tissues and the artificial material is of critical importance. The research focuses on stem cells, design of material surfaces, and mechanisms of cell adhesion. For the third time around 200 scientists met in Rostock, Germany for the international symposium “Interface Biology of Implants.” The aim of the symposium is to promote the interdisciplinary dialogue between the scientists from the different disciplines to develop smart implants for medical use. In addition, researchers from basic sciences, notably cell biology presented new findings concerning mechanisms of cell adhesion to stimulate research in the applied field of implant technology.Key words: interface, implant, stem cells, adhesion, mechanics, surface, biomaterialMedical implants play a growing role in routine clinical practice. In addition to replace or stabilize injured tissue permanently or transiently, the application of implant materials to stimulate the regeneration of tissue is becoming a challenge in the field of regenerative medicine. The use of implant materials is based on the idea that biomaterials function not only as mechanical support for cells and tissue but also provide a matrix to induce signal transduction in the cells that control complex molecular mechanisms responsible for proliferation und differentiation. In this context, the interface between artificial materials and living cells or tissue is an exciting field of great scientific interest and constitutes one of the most dynamic and expanding field in science and technology. Progress in this field is mainly driven by the fundamental importance for clinical applications. The research is characterized by a multidisciplinary collaboration between physics, engineers, biologists and clinicians.In May 2009, for the third time after 2003 and 2006 around 200 scientists met in Rostock-Warnemünde for the symposium “Interface Biology of Implants” to discuss biointerface processes at a fundamental level. The main goals of this symposium are to simulate the interdisciplinary dialogue between scientists of the different disciplines and to introduce current knowledge of basic research in cell biology and material science into the applied field of implant technology. The programme was organized in invited presentations of 20 internationally renowned scientists and complemented by short talks of mostly young scientists selected from the submitted abstracts. In addition, 80 posters presented latest results in this multidisciplinary field.The symposium was opened with a keynote lecture presented by Hartmut Hildebrand (Lille). He gave an overview about the 7,000 years old history of application of implant materials. Rare photographs were shown which demonstrated that in these early times prostheses mainly made from metallic materials were used to restore teeth, extremities and the skull of the human body. These old documents stressed the historical relevance of medical application of implant materials.The symposium on two days was composed of four sessions covering the interdisciplinary research in the field. The session “Stem cells and biomaterials” discussed the biological response and signalling mechanism of stem cells in the interaction with a material surface. The session “Bioactivation of implant surfaces” focussed on the tailoring of surfaces to control the cell physiology. To stimulate the field by recent data in basic cell biology, talks were presented in the third session, dealing with molecular mechanisms involved in cell adhesion. A special session dealt with the role and mechanism of controlling cells by mechanics.     

谈中国植物科学基础研究与农业发展

该文讨论了加强植物科学基础研究的必要性及其对我国农业发展的重要影响。为了更好地为中国的农业发展服务,进一步加强植物科学基础研究非常重要。为了促进植物科学的发展,我国既要积极参与国际竞争,又要重视知识创新、技术发展以及技术平台建设等多个方面,还要重视传统学科如植物分类学等的发展。过去10年间,我们见证了中国科学家在植物科学领域取得的重要成就,随着越来越多的高水平人才回国,建议国家增加投入支持我国的植物科学基础研究。     

谈中国植物科学基础研究与农业发展

该文讨论了加强植物科学基础研究的必要性及其对我国农业发展的重要影响。为了更好地为中国的农业发展服务, 进一步加强植物科学基础研究非常重要。为了促进植物科学的发展, 我国既要积极参与国际竞争, 又要重视知识创新、技术发展以及技术平台建设等多个方面, 还要重视传统学科如植物分类学等的发展。过去10年间, 我们见证了中国科学家在植物科学领域取得的重要成就, 随着越来越多的高水平人才回国, 建议国家增加投入支持我国的植物科学基础研究。     

The Medawar Lecture 1998 is science dangerous?

The idea that science is dangerous is deeply embedded in our culture, particularly in literature, yet science provides the best way of understanding the world. Science is not the same as technology. In contrast to technology, reliable scientific knowledge is value-free and has no moral or ethical value. Scientists are not responsible for the technological applications of science; the very nature of science is that it is not possible to predict what will be discovered or how these discoveries could be applied. The obligation of scientists is to make public both any social implications of their work and its technological applications. A rare case of immoral science was eugenics. The image of Frankenstein has been turned by the media into genetic pornography, but neither cloning nor stem cells or gene therapy raise new ethical issues. There are no areas of research that are so socially sensitive that research into them should be proscribed. We have to rely on the many institutions of a democratic society: parliament, a free and vigorous press, affected groups and the scientists themselves. That is why programmes for the public understanding of science are so important. Alas, we still do not know how best to do this.     

A conceptual framework for understanding the perspectives on the causes of the science–practice gap in ecology and conservation

Applying scientific knowledge to confront societal challenges is a difficult task, an issue known as the science–practice gap. In Ecology and Conservation, scientific evidence has been seldom used directly to support decision‐making, despite calls for an increasing role of ecological science in developing solutions for a sustainable future. To date, multiple causes of the science–practice gap and diverse approaches to link science and practice in Ecology and Conservation have been proposed. To foster a transparent debate and broaden our understanding of the difficulties of using scientific knowledge, we reviewed the perceived causes of the science–practice gap, aiming to: (i) identify the perspectives of ecologists and conservation scientists on this problem, (ii) evaluate the predominance of these perspectives over time and across journals, and (iii) assess them in light of disciplines studying the role of science in decision‐making. We based our review on 1563 sentences describing causes of the science–practice gap extracted from 122 articles and on discussions with eight scientists on how to classify these sentences. The resulting process‐based framework describes three distinct perspectives on the relevant processes, knowledge and actors in the science–practice interface. The most common perspective assumes only scientific knowledge should support practice, perceiving a one‐way knowledge flow from science to practice and recognizing flaws in knowledge generation, communication, and/or use. The second assumes that both scientists and decision‐makers should contribute to support practice, perceiving a two‐way knowledge flow between science and practice through joint knowledge‐production/integration processes, which, for several reasons, are perceived to occur infrequently. The last perspective was very rare, and assumes scientists should put their results into practice, but they rarely do. Some causes (e.g. cultural differences between scientists and decision‐makers) are shared with other disciplines, while others seem specific to Ecology and Conservation (e.g. inadequate research scales). All identified causes require one of three general types of solutions, depending on whether the causal factor can (e.g. inadequate research questions) or cannot (e.g. scientific uncertainty) be changed, or if misconceptions (e.g. undervaluing abstract knowledge) should be solved. The unchanged predominance of the one‐way perspective over time may be associated with the prestige of evidence‐based conservation and suggests that debates in Ecology and Conservation lag behind trends in other disciplines towards bidirectional views ascribing larger roles to decision‐makers. In turn, the two‐way perspective seems primarily restricted to research traditions historically isolated from mainstream conservation biology. All perspectives represented superficial views of decision‐making by not accounting for limits to human rationality, complexity of decision‐making contexts, fuzzy science–practice boundaries, ambiguity brought about by science, and different types of knowledge use. However, joint knowledge‐production processes from the two‐way perspective can potentially allow for democratic decision‐making processes, explicit discussions of values and multiple types of science use. To broaden our understanding of the interface and foster productive science–practice linkages, we argue for dialogue among different research traditions within Ecology and Conservation, joint knowledge‐production processes between scientists and decision‐makers and interdisciplinarity across Ecology, Conservation and Political Science in both research and education.     

生物医学工程的研究范围

“生物医学工程”这个词汇蕴含了三个专业领域的相互影响：生物学（最广义的范围讲是基于物理学和化学的一门基础科学）、医学（治疗疾病的科学）和工程学（设计及建造对人类有用的物品的科学）。在20世纪50年代中期,我被任命组建一个实验室,这个实验室需要结合这三大学科,并致力于听觉研究。在过去的50年中,我们的实验室（由麻省理工大学、哈佛大学、麻省总医院及麻省眼耳医院共同管理）树立了一个优秀的范例,证明虽然有一些实际的困难,科学家、临床医师和工程师们仍然可以很好地合作。我们的经验之一是,往往一些最成功的发现是基于对基本科学知识的发展,而不是来源于对特定临床需要的靶向性研究。然而,“研究与发展”常常需要有技术创新教育背景,并能与数个领域的专家充分交流的特殊工作人员。因此,在目前这个环境与社会问题需要传统意义上非生物医学工程领域的技术专家的时代,生物医学工程师的培养问题及资源应如何在发达国家与发展中国家之间分配的问题的探讨,都具有十分重要的现实意义。     

Why we need more basic biology research,not less

Much of the spectacular progress in biomedical science over the last half-century is the direct consequence of the work of thousands of basic scientists whose primary goal was understanding of the fundamental working of living things. Despite this, many politicians, funders, and even scientists have come to believe that the pace of successful applications to medical diagnosis and therapy is limited by our willingness to focus directly on human health, rather than a continuing deficit of understanding. By this theory, curiosity-driven research, aimed at understanding, is no longer important or even useful. What is advocated instead is “translational” research aimed directly at treating disease. I believe this idea to be deeply mistaken. Recent history suggests instead that what we have learned in the last 50 years is only the beginning. The way forward is to invest more in basic science, not less.     

Prospects for translational regenerative medicine

Translational medicine is an evolutional concept that encompasses the rapid translation of basic research for use in clinical disease diagnosis, prevention and treatment. It follows the idea "from bench to bedside and back", and hence relies on cooperation between laboratory research and clinical care. In the past decade, translational medicine has received unprecedented attention from scientists and clinicians and its fundamental principles have penetrated throughout biomedicine, offering a sign post that guides modern medical research toward a patient-centered focus. Translational regenerative medicine is still in its infancy, and significant basic research investment has not yet achieved satisfactory clinical outcomes for patients. In particular, there are many challenges associated with the use of cell- and tissue-based products for clinical therapies. This review summarizes the transformation and global progress in translational medicine over the past decade. The current obstacles and opportunities in translational regenerative medicine are outlined in the context of stem cell therapy and tissue engineering for the safe and effective regeneration of functional tissue. This review highlights the requirement for multi-disciplinary and inter-disciplinary cooperation to ensure the development of the best possible regenerative therapies within the shortest timeframe possible for the greatest patient benefit.     

Reinventing Biostatistics Education for Basic Scientists

Numerous studies demonstrating that statistical errors are common in basic science publications have led to calls to improve statistical training for basic scientists. In this article, we sought to evaluate statistical requirements for PhD training and to identify opportunities for improving biostatistics education in the basic sciences. We provide recommendations for improving statistics training for basic biomedical scientists, including: 1. Encouraging departments to require statistics training, 2. Tailoring coursework to the students’ fields of research, and 3. Developing tools and strategies to promote education and dissemination of statistical knowledge. We also provide a list of statistical considerations that should be addressed in statistics education for basic scientists.     

The myeloneuropathies of Jamaica

This article summarizes the present state of knowledge of TSP/HAM as it is seen in Jamaica. It reviews the historical and clinical aspects of the disease, and shows how the discovery of HTLV-I has generated research in several countries and contributed to a better understanding of the disease. It highlights the need for continued collaboration between basic scientists and clinical neurologists in order that the dilemmas relating to therapy and pathogenicity may be successfully addressed.     

Citizen Science

Citizen science Citizen science is performed on a honorary basis. Citizen scientists (”Citizen Science proper“) have no professional employment in the relevant field of research and differ very much in their educational background, specific knowledge and amount of time dedicated to the subject of research. Today, citizen science has become especially important in some fields neglected by professional science, e.g. regional research. Recently, another form of citizen science has gained much attention, in which usually many citizen scientist are active (”Citizen Science light“). Internet, smartphone and georeferencing by GPS are important tools for collecting, documenting and communicating the observation data. Besides the scientific results, social relevance through participation and information of citizens (e.g. for conservation issues) play a very important role in these projects. The recently strongly increasing interest in and contribution to citizen science plays an important role to strengthen the link and communication between science and society.     

Brain metastasis in lung cancer: Building a molecular and systems-level understanding to improve outcomes

Lung cancer is a clinically difficult disease with rising disease burden around the world. Unfortunately, most lung cancers present at a clinically advanced stage. Of these cancers, many also present with brain metastasis which complicates the clinical picture. This review summarizes current knowledge on the molecular basis of lung cancer brain metastases. We start from the clinical perspective, aiming to provide a clinical context for a significant problem that requires much deeper scientific investigation. We review new research governing the metastatic process, including tumor cell signaling, establishment of a receptive tumor niches in the brain and evaluate potential new therapeutic options that take advantage of these new scientific advances.Lung cancer remains the largest single cause of cancer mortality in the United States (Siegel et al., 2015). This continues to be the clinical picture despite significant advances in therapy, including the advent of targeted molecular therapies and newly adopted immunotherapies for certain subtypes of lung cancer. In the vast majority of cases, lung cancer presents as advanced disease; in many instances, this advanced disease state is intimately associated with micro and macrometastatic disease (Goldberg et al., 2015). For both non-small cell lung cancer and small cell lung cancer patients, the predominant metastatic site is the brain, with up to 68% of patients with mediastinal lymph node metastasis eventually demonstrating brain metastasis (Wang et al., 2009).The frequency (incidence) of brain metastasis is highest in lung cancers, relative to other common epithelial malignancies (Schouten et al., 2002). Other studies have attempted to predict the risk of brain metastasis in the setting of previously non-metastatic disease. One of the largest studies to do this, analyzing historical data from 1973 to 2011 using the SEER database revealed a 9% risk of patients with previously non-metastatic NSCLC developing brain metastasis over the course of their disease, while 18% of small cell lung cancer patients without previous metastasis went on to develop brain metastasis as their disease progressed (Goncalves et al., 2016).The reasons underlying this predilection for the central nervous system, as well as the recent increase in the frequency of brain metastasis identified in patients remain important questions for both clinicians and basic scientists. More than ever, the question of how brain metastasis develop and how they can be treated and managed requires the involvement of interdisciplinary teams—and more importantly—scientists who are capable of thinking like clinicians and clinicians who are capable of thinking like scientists. This review aims to present a translational perspective on brain metastasis. We will investigate the scope of the problem of brain metastasis and the current management of the metastatic disease process in lung cancer. From this clinical starting point, we will investigate the literature surrounding the molecular underpinnings of lung tumor metastasis and seek to understand the process from a biological perspective to generate new hypotheses.     

Is bigger better?

To close the gap between research and development, a number of funding organizations focus their efforts on large, translations research projects rather than small research teams and individual scientists. Yet, as Paul van Helden argues, if the support for small, investigator-driven research decreases, there will soon be a dearth of novel discoveries for large research groups to explore.What is medical science all about? Surely it is about the value chain, which begins with basic research and ends—if there is an end—with a useful product. There is a widespread perception that scientists do a lot of basic research, but neglect the application of their findings. To remedy this, a number of organizations and philanthropists have become dedicated advocates of applied or translational research and preferentially fund large consortia rather than small teams or individual scientists. Yet, this is only the latest round in the never-ending debate about how to optimize research. The question remains whether large teams, small groups or individuals are better at making ‘discoveries''.To some extent, a scientific breakthrough depends on the nature of the research. Einstein worked largely alone, and the development of E = mc² is a case in point. He put together insights from many researchers to produce his breakthrough, which has subsequently required teams of scientists to apply. Similarly, drug development may require only an individual or a small team to make the initial discovery. However, it needs many individuals to develop a candidate compound and large teams to conduct clinical trials. On the other hand, Darwin could be seen to have worked the other way around: he had an initial ‘team'' of ‘field assistants''—including the crew of HMS Beagle—but he produced his seminal work essentially alone.Consortium funding is of course attractive for researchers because of the time-scale and the amount of money involved. Clinical trials or large research units may get financial support for 10 years or even longer and in the range of millions of dollars. However, organizations that provide funding on such a large scale require extensive and detailed planning from researchers. The work is subject to frequent reporting and review and often carries a large administrative burden. It has come to the point where this oversight threatens academic freedom. Principal investigators who try to conduct experiments outside the original plan, even if they make sense, lose their funding. Under such conditions, administrative officials are often not there to serve, but to govern.There is a widespread perception that small teams are more productive in terms of published papers. But large-scale science often generates outcomes and product value that a small team cannot. We therefore need both. The problem is the low level of funding for individual scientists and small teams and the resulting cut-throat competition for limited resources. This draws too many researchers to large consortia, which, if successful, can become comfort zones or, if they crash and burn, can cause serious damage.Other factors should also inform our deliberations about the size of research teams and consortia. Which is the better environment in which to train the next generation of scientists? By definition, research should question scientific dogmas and foster innovative thinking. Will a large consortium be able to achieve or even tolerate this?Perhaps these trends can be ascribed to generational differences. Neil Howe described people born between 1943 and 1980 as obsessed with values, individually strong and individualistic, whereas the younger folks born after 1981 place more trust in strong institutions that are seen to be moving society somewhere. If this is true, we can predict that the consortium approach is here to stay, at least for some time. Perhaps the emergence of large-scale science is driven by strong—maybe dictatorial—older individuals and arranged to accommodate the younger generation. If so, it is a win–win situation: we know the value of networking and interacting with others, which comes naturally in the ‘online age''.A down side of large groups is the loss of individual career development. The number of authors per paper has increased constantly. Who does the work and who gets the honour? There is often little recognition for the contribution of most people to publications that arise from large consortia, and it is difficult for peer-reviewers to assess individual contribution. We must take care that we measure what we value and not value what we measure.While it is clear that both large and small groups are essential, good management and balance is required. An alarming trend in my opinion is the inclination to fund new sites for clinical trials, to the detriment of existing facilities. This does not seem to be reasonable or the best use of scarce resources.In the long-term interest of science, we need to consider the correlation of major breakthroughs compared to incremental science with the size of the research group. This is hard to measure, but we must not forget that basic research produces the first leads that are then developed further into products. If the funding for basic science decreases, there will soon be a dearth of topics for ‘big science''.Is there a way out of this dilemma? I would like to suggest that organizations currently funding large consortia allow investigators to set aside a percentage of the money to support basic, curiosity-driven research within these consortia. If they do not rethink their funding strategy, these organizations may find with time that there are few novel discoveries for large groups to explore.