Eye-tracking with nonhuman primates is now more accessible than ever before

Human and nonhuman primates rely almost exclusively on vision for social communication. Therefore, tracking eye movements and examining visual scan paths can provide a wealth of information about many aspects of primate social information processing. Although eye-tracking techniques have been utilized with humans for some time, similar studies in nonhuman primates have been less frequent over recent decades. This has largely been owing to the need for invasive manipulations, such as the surgical implantation of devices to limit head movement, which may not be possible in some laboratories or at some universities, or may not be congruent with some experimental aims (i.e., longitudinal studies). It is important for all nonhuman primate researchers interested in visual information processing or operant behavior to realize that such invasive procedures are no longer necessary. Here, we briefly describe new methods for fully noninvasive video eye-tracking with adult rhesus monkeys (Macaca mulatta). We also describe training protocols that require only ～30 days to accomplish and quality control measures that promote reliable data collection. It is our hope that this brief overview will reacquaint nonhuman primate researchers with the benefits of eye-tracking and promote expanded use of this powerful methodology.     

On the implementation of a wrinkling,hyperelastic membrane model for skin and other materials

A number of researchers have studied the mechanical properties of skin and developed constitutive models to describe its behaviour. Typically, many of these studies have concentrated on the uniaxial tensile behaviour of the skin, on the grounds that it will wrinkle under in-plane compression and have minimal stiffness. However, although there is a substantial body of literature on wrinkling models, the practical implementation of such a model of skin in a finite element setting has not been widely addressed. This paper presents computational details of a wrinkling, hyperelastic membrane model and aspects of its implementation and areas requiring further research are discussed. The model is based on an Ogden constitutive model, which provides accurate results at moderate strains, but it would be straightforward to implement other constitutive models such as the Fung or Arruda–Boyce models using a similar approach. Example results are presented which demonstrate that the model can provide a good approximation to experimental data. The model has many other possible applications, both for biological materials and for other thin hyperelastic membranes.     

Training in High-Throughput Sequencing: Common Guidelines to Enable Material Sharing,Dissemination, and Reusability

The advancement of high-throughput sequencing (HTS) technologies and the rapid development of numerous analysis algorithms and pipelines in this field has resulted in an unprecedentedly high demand for training scientists in HTS data analysis. Embarking on developing new training materials is challenging for many reasons. Trainers often do not have prior experience in preparing or delivering such materials and struggle to keep them up to date. A repository of curated HTS training materials would support trainers in materials preparation, reduce the duplication of effort by increasing the usage of existing materials, and allow for the sharing of teaching experience among the HTS trainers’ community. To achieve this, we have developed a strategy for materials’ curation and dissemination. Standards for describing training materials have been proposed and applied to the curation of existing materials. A Git repository has been set up for sharing annotated materials that can now be reused, modified, or incorporated into new courses. This repository uses Git; hence, it is decentralized and self-managed by the community and can be forked/built-upon by all users. The repository is accessible at http://bioinformatics.upsc.se/htmr.     

Medical Researchers' Ancillary Care Obligations: The Relationship‐Based Approach

In this article, I provide a new account of the basis of medical researchers' ancillary care obligations. Ancillary care in medical research, or medical care that research participants need but that is not required for the validity or safety of a study or to redress research injuries, is a topic that has drawn increasing attention in research ethics over the last ten years. My view, the relationship‐based approach, improves on the main existing theory, Richardson and Belsky's ‘partial‐entrustment model’, by avoiding its problematic restriction on the scope of health needs for which researchers could be obligated to provide ancillary care. Instead, it grounds ancillary care obligations in a wide range of morally relevant features of the researcher‐participant relationship, including the level of engagement between researchers and participants, and weighs these factors against each other. I argue that the level of engagement, that is, the duration and intensity of interactions, between researchers and participants matters for ancillary care because of its connection to the meaningfulness of a relationship, and I suggest that other morally relevant features can be grounded in researchers' role obligations.     

Teaching and training in geriatric medicine in the European Union

In 1993 about 20% of the population in the 15 'old' member countries of the European Union (EU) was over 60 years of age and this percentage will increase to more than 25% in 2020. These developments play a key role for the investments in education and training to meet societies needs for health care services. In 2002 about 25% of the medical students in the 'old' EU did not receive any education in geriatric medicine. A question is who will provide the services for older people in related areas, like social care, community care, acute care in the hospitals, long-term care, permanent care and care for psychiatric patients? Geriatric medicine has been recognized as an independent specialty in 8 of the 15 member countries of the 'old' EU. In all EU member states the governments are autonomous regarding all aspects of health care services, including the recognition of specialties and specialist training programmes. A two years training in internal medicine has been recommended in the EU, followed by another four years of training in geriatric medicine. The specialist training has a hospital oriented character, however, it includes also community care and other institutionalised care like nursing homes. The curriculum should contain: biological, social, psychological and medical aspects of common diseases and disturbances in older people. A problem in many EU countries is the shortage of well trained researchers and leading persons for academic positions for geriatric medicine. In a number of countries chairs at the universities remain vacant for long periods of time or even disappear. Good services in the health care for older people need a high quality curriculum and training programme.     

Early warning systems for malaria in Africa: from blueprint to practice

Although the development of early warning systems for malaria has been advocated by international agencies and academic researchers for many years, practical progress in this area has been relatively modest. In two recent articles, Thomson et al. provide new evidence that models of malaria incidence that incorporate monitored or predicted climate can provide early warnings of epidemics one to five months in advance in semi-arid areas. Although the potential benefits of these models in terms of improved management of epidemics are clear, several technical and practical hurdles still need to be overcome before the models can be widely integrated into routine malaria-control strategies.     

GOBLET: The Global Organisation for Bioinformatics Learning,Education and Training

In recent years, high-throughput technologies have brought big data to the life sciences. The march of progress has been rapid, leaving in its wake a demand for courses in data analysis, data stewardship, computing fundamentals, etc., a need that universities have not yet been able to satisfy—paradoxically, many are actually closing “niche” bioinformatics courses at a time of critical need. The impact of this is being felt across continents, as many students and early-stage researchers are being left without appropriate skills to manage, analyse, and interpret their data with confidence. This situation has galvanised a group of scientists to address the problems on an international scale. For the first time, bioinformatics educators and trainers across the globe have come together to address common needs, rising above institutional and international boundaries to cooperate in sharing bioinformatics training expertise, experience, and resources, aiming to put ad hoc training practices on a more professional footing for the benefit of all.     

Pectinase Activity Determination: An Early Deceleration in the Release of Reducing Sugars Throws a Spanner in the Works!

Recently, it has been suggested that pectinases could be used to hydrolyze pectin in biorefineries based on pectin-rich agro-industrial wastes. However, for this to be viable, the cost of their production would need to be lowered significantly. In fact, over the last few decades, there have been many attempts to improve pectinase production by existing strains or to screen for new strains from environmental isolates. In these studies, it is necessary to measure pectinase activities. Many researchers use single-time-point assays that involve incubation of pectinolytic extracts with pectic substrates for a fixed time, followed by determination of the liberated reducing sugars. However, different researchers use quite different conditions for this assay. Furthermore, no attention has been given to the reaction profile during the assay. In the current work, we show, for the first time, that a significant deceleration of the rate of liberation of reducing sugars occurs over the first ten minutes of the reaction. As a consequence, the incubation time used in a single-time-point assay has a large effect on the value obtained for the activity. In fact, we demonstrate that, depending on the particular combination of incubation time, pectin concentration and reaction temperature, the same extract could be reported to have activities that differ by an order of magnitude. In addition, we show that the relative activities obtained with polygalacturonic acid do not correlate with those obtained with pectin. We conclude that it is currently impossible to make meaningful comparisons between pectinase activities reported in the literature by workers who have used different assay conditions. Therefore there is an urgent need for the development of a standardized assay for evaluating the saccharification potential of pectinase complexes.     

A prospective multiple case study of the impact of emerging scientific evidence on established colorectal cancer screening programs: a study protocol

In this editorial, we reflect on the arguments for starting a scientific society focused on research on how to improve healthcare. This society would take an inclusive approach to what constitutes healthcare. For instance, it should include mental health healthcare, treatment for substance abuse, the work of allied health professions, and preventive healthcare. The society would be open to researchers from all traditions. Thus, we take an inclusive approach to what constitutes scientific research, as long as it uses rigorous methods, is focused on improving healthcare, and aims at knowledge that can be transferred across settings. The society would primarily target scientific researchers but would invite others with an interest in this area of research, regardless of their discipline, position, field of application, or group affiliation (e.g., improvement science, behavioral medicine, knowledge translation). A society would need fruitful collaboration with related societies and organizations, which may include having combined meetings. Special links may be developed with one or more journals. A website to provide information on relevant resources, events, and training opportunities is another key activity. It would also provide a voice for the field at funding agencies, political arenas, and similar institutions. An organizational structure and financial resources are required to develop and run these activities. Our aim is to start an international debate, to discover if we can establish a shared vision across academics and stakeholders engaged with creating scientific knowledge on how to improve healthcare. We invite readers to express their views in the online questionnaire accessed by following the URL link provided at the end of the editorial.     

多组分反应在吡咯衍生物合成中的应用进展

多组分反应(Multicomponent Coupling Reactions,MCRs)是将三种或三种以上的相对简单的原料加入"一锅煮"反应中,不经过中间体分离而直接得到结构复杂的分子的方法。具有操作简单、原料易得、环境友好等优点。多组分反应发展至今,已经在包括药物合成的多个领域中起到了重要作用。吡咯衍生物作为一类在自然界中广泛分布、有着重要生物医药价值和材料科学价值的重要化合物,其合成方法一直是有机合成研究中的热点之一。近年来用于合成吡咯衍生物的多组分反应也不断地被报道。多组分反应能够很好地解决传统吡咯合成路线中取代基引入的问题并能提高反应收率,为吡咯衍生物的合成与研究带来便利。本文从合成方法上概述了近年来多组分反应在吡咯合成中的应用,为合成已有吡咯衍生物和探寻全新结构的吡咯衍生物提供合成方法上的新思路。     

Future trends in nitrogen research

N research effort has undergone major changes over recent decades with changing emphasis because of environmental problems and issues. This driving force, coupled with a universal desire to improve N-use efficiency, appreciation of the importance of maintaining soil resource quality and a need to provide integrated landscape managements, will continue to prompt new research areas and issues for study. Already, much information has been provided and new approaches and needs defined. It will be essential in future research to take full note of the many interactions that occur and to provide a mechanistic basis so that scaling of effects can be undertaken with the appropriate simplification without being superficial. Examples of interactions, as well as fundamental gaps in the basic processes are discussed and needs for future research identified.     

The NIDDK Information Network: A Community Portal for Finding Data,Materials, and Tools for Researchers Studying Diabetes,Digestive, and Kidney Diseases

The NIDDK Information Network (dkNET; http://dknet.org) was launched to serve the needs of basic and clinical investigators in metabolic, digestive and kidney disease by facilitating access to research resources that advance the mission of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). By research resources, we mean the multitude of data, software tools, materials, services, projects and organizations available to researchers in the public domain. Most of these are accessed via web-accessible databases or web portals, each developed, designed and maintained by numerous different projects, organizations and individuals. While many of the large government funded databases, maintained by agencies such as European Bioinformatics Institute and the National Center for Biotechnology Information, are well known to researchers, many more that have been developed by and for the biomedical research community are unknown or underutilized. At least part of the problem is the nature of dynamic databases, which are considered part of the “hidden” web, that is, content that is not easily accessed by search engines. dkNET was created specifically to address the challenge of connecting researchers to research resources via these types of community databases and web portals. dkNET functions as a “search engine for data”, searching across millions of database records contained in hundreds of biomedical databases developed and maintained by independent projects around the world. A primary focus of dkNET are centers and projects specifically created to provide high quality data and resources to NIDDK researchers. Through the novel data ingest process used in dkNET, additional data sources can easily be incorporated, allowing it to scale with the growth of digital data and the needs of the dkNET community. Here, we provide an overview of the dkNET portal and its functions. We show how dkNET can be used to address a variety of use cases that involve searching for research resources.     

The science,art and business of successful bioherbicides

In this article, the critical issues in the production of successful bioherbicides have been defined in an effort to stimulate discussion on the underlying science, art of formulation and fermentation and the business of producing and marketing of bioherbicides. To a large extent the science of bioherbicides has focussed on epidemiology, although the enormous potential of molecular technology to improve the efficacy of these agents is being investigated. Some of this potential is coming to fruition in terms of development of tools for the identification and tracking of biological controls, although the genetic modification of biological control agents is still in its infancy. On the other hand, knowledge in the areas of formulation and fermentation is often proprietary in nature. This makes it critical for researchers to work in collaboration with other researchers or industry in these areas. The importance of the appropriate involvement of industry and commercialization partners early in the development process should not be underestimated. Although ad hoc research into biological control should not be discouraged, researchers should be encouraged to think carefully before they postulate on the potential of a bioherbicide based purely on preliminary isolation and pathogenicity testing. As much of the research is specific to a single pathogen/host system, the way ahead in bioherbicide research would appear to be the development of consortia or research nodes in which scientists and business people with backgrounds in the discovery, development and commercialization of biopesticides work collaboratively on a number of projects. There has been movement towards this type of model in countries such as Canada, USA and New Zealand although other countries lag behind. Interestingly, all five of the recently registered bioherbicides in the U.S. and Canada were developed and registered by small-business enterprises or a subsidiary of enterprises with no prior record in pesticide development.The constraints to bioherbicides are not in the science, art or business: it is in bringing all of these aspects together in an accessible way and the sharing of intellectual property in an equitable fashion. A new model for the commercialization of bioherbicides should build on currently established research networks, but need to have a stronger link to industry (especially small–medium enterprises) and requires funding for infrastructure and personnel. This funding needs to come from the public sector. Industry is interested in engaging this type of research, but they need to be reassured that the approach is feasible, economic and realistic and that the resources required are available.     

The versatile worm: genetic and genomic resources for Caenorhabditis elegans research

Since its establishment as a model organism, Caenorhabditis elegans has been an invaluable tool for biological research. An immense spectrum of questions can be addressed using this small nematode, making it one of the most versatile and exciting model organisms. Although the many tools and resources developed by the C. elegans community greatly facilitate new discoveries, they can also overwhelm newcomers to the field. This Review aims to familiarize new worm researchers with the main resources, and help them to select the tools that are best suited for their needs. We also hope that it will be helpful in identifying new research opportunities and will promote the development of additional resources.     

To clone or not to clone: method analysis for retrieving consensus sequences in ancient DNA samples

The challenges associated with the retrieval and authentication of ancient DNA (aDNA) evidence are principally due to post-mortem damage which makes ancient samples particularly prone to contamination from "modern" DNA sources. The necessity for authentication of results has led many aDNA researchers to adopt methods considered to be "gold standards" in the field, including cloning aDNA amplicons as opposed to directly sequencing them. However, no standardized protocol has emerged regarding the necessary number of clones to sequence, how a consensus sequence is most appropriately derived, or how results should be reported in the literature. In addition, there has been no systematic demonstration of the degree to which direct sequences are affected by damage or whether direct sequencing would provide disparate results from a consensus of clones.To address this issue, a comparative study was designed to examine both cloned and direct sequences amplified from ～3,500 year-old ancient northern fur seal DNA extracts. Majority rules and the Consensus Confidence Program were used to generate consensus sequences for each individual from the cloned sequences, which exhibited damage at 31 of 139 base pairs across all clones. In no instance did the consensus of clones differ from the direct sequence. This study demonstrates that, when appropriate, cloning need not be the default method, but instead, should be used as a measure of authentication on a case-by-case basis, especially when this practice adds time and cost to studies where it may be superfluous.     

The dilemma of the honest researcher

Most agree that without honest and trustworthy practitioners, research has no value. Yet high standards present a dilemma for honest researchers, because successful practices often clash with ethically impeccable behaviour.The honesty and trustworthiness of researchers is increasingly scrutinized as high-profile stories of research misconduct become public. Researchers, politicians and funders agree that dishonest and untrustworthy research has no value. However, the standards for judging integrity and the core values to which researchers should adhere are less clear.To help efforts to promote research integrity around the world, the second World Conference on Research Integrity in Singapore developed a statement as a checklist for researchers to assess their own behaviour, and to provide a framework for developing national and organizational guides, codes of conduct and research-integrity policies (World Conferences on Research Integrity, 2010).Yet standards for responsible behaviour in research pose a dilemma for the honest researcher, because many commonly accepted practices are at odds with ‘ideal'' behaviour. Although outright dishonesty is not the norm and for the most part not tolerated, less-than-honest behaviour is, and might even be necessary in today''s competitive research environment.To be funded, research must be innovative and important. The need to ‘sell'' a grant proposal can encourage overselling of the significance of data or the importance of likely outcomes. Support for basic research to decode the human genome was gained on the basis of claims of benefits to human health that many now regard as overly optimistic and unrealistic (Marshall, 2011). Clinical trials are often inconclusive, owing to overestimation of the effects of treatment (Djulbegovic et al, 2010). However, an honest researcher who makes modest claims or honestly describes likely obstacles might not be as competitive as one who provides the most-generous estimates of long-term benefits.The many rules that define best practice can seem to be counter-productive and burdensome. Securing funding requires the provision of compelling preliminary data, but research agencies often do not fund mere data collection. Is it therefore acceptable to collect preliminary data for the next project with funds awarded for the current project? If an institutional review board or research ethics committee places seemingly burdensome requirements on research with human subjects, is it acceptable to bend the rules to complete the project? Studies have shown that a significant number of researchers use this excuse for minor violations of requirements for human subjects (Keith-Spiegel & Koocher, 2005).Ideally, research should be collaborative. Public interest should take precedence over self interest, once intellectual and property interests have been protected. Nonetheless, researchers sometimes do not share information—a practice that has been shown to slow progress (Blumenthal, 2006). It is also alleged, but has not been confirmed empirically, that researchers sometimes provide insufficient or misleading information to slow the work of competitors. On the receiving end, researchers have been known to take unfair advantage of privileged information from peer review.Honesty in research is particularly strained during formal publication. Less-than-honest practices include adding honorary names to the author list; failing to include the names of individuals who made significant contributions, such as industry ghostwriters; misrepresenting findings in abstracts; dividing one project into several publications to enhance a resume; failing to list conflicts of interest; and publishing the same work more than once without adequate notification. Research publications are sliced, diced and wrapped in many ways. When these practices come to be common, it is difficult for the honest researcher not to fall in line.However, before falling into line too quickly, there are two consequences that scientists ought to consider. All questionable practices could, under particular circumstances, be classed as misconduct, particularly if they are engaged in widely and often. One small compromise might not be important, but several larger ones could be. Moreover, acting less than honestly can be a first step down a slippery slope towards misconduct. When researchers engage in common, but not necessarily proper, practices, they need to be aware of what they are doing and the possible consequences. Right and wrong can be too easily confused.Misconduct in research was not new when it first received public attention in the 1970s and 1980s. The fact that it had been either ignored or tolerated by researchers and research institutions led governments around the world to implement regulations. Much the same scenario has followed in relation to conflicts of interest, dual-use research, and other areas in which integrity and the professional conduct of researchers have been questioned. Researchers need to face up to the conflict between professed commitments to high standards for research integrity and widespread tolerance of practices that fall short of these standards. Doing so is essential to preserving public confidence in research and to reducing, if not eliminating, the dilemma faced by the honest researcher.     

Strain improvement in actinomycetes in the postgenomic era

With the recent advances in DNA sequencing technologies, it is now feasible to sequence multiple actinomycete genomes rapidly and inexpensively. An important observation that emerged from early Streptomyces genome sequencing projects was that each strain contains genes that encode 20 or more potential secondary metabolites, only a fraction of which are expressed during fermentation. More recently, this observation has been extended to many other actinomycetes with large genomes. The discovery of a wealth of orphan or cryptic secondary metabolite biosynthetic gene clusters has suggested that sequencing large numbers of actinomycete genomes may provide the starting materials for a productive new approach to discover novel secondary metabolites. The key issue for this approach to be successful is to find ways to turn on or turn up the expression of cryptic or poorly expressed pathways to provide material for structure elucidation and biological testing. In this review, I discuss several genetic approaches that are potentially applicable to many actinomycetes for this application.     

Strengthening the scientific contribution of botanic gardens to the second phase of the Global Strategy for Plant Conservation

The need for action on the global environment is now well understood and governments, agencies, non-governmental organizations and botanic gardens have all been working in their various ways to promote environmental sustainability and reduce species and habitat loss for at least 10–20 years. The Global Strategy for Plant Conservation (GSPC) has been widely adopted, particularly by the botanic garden community, and has resulted in many successes despite failing to achieve its ultimate goal of halting the loss of plant biodiversity. The objectives and targets for Phase 2 of the GSPC, running from 2010 to 2020, mirror those of Phase 1 and had been largely agreed prior to their formal adoption at the Conference of the Parties to the Convention on Biological Diversity in Nagoya in October 2010. However, to be successful, the scientific contribution of botanic gardens needs to be strengthened, as does government policy and commitment. Botanic garden research to underpin conservation action, including the role of botanic garden horticulture, training and international capacity building, has a major part to play and needs to be better understood and better coordinated. We provide examples based on the experience of the Royal Botanic Garden Edinburgh in the UK and overseas. Government policy, at national and international levels, needs to reflect the fundamental importance of plant diversity in maintaining the biosphere and supporting humanity. The commitment of significant new resources is an essential prerequisite for success, but this needs to be well coordinated, inclusive of all stakeholders and carefully targeted. A further challenge is the need to integrate better the plant diversity-related activities of what are currently diverse and disconnected sectors, including agriculture, forestry, protected area management and botanic gardens.     

小鼠巨噬细胞RAW264.7 的培养技巧及经验总结

RAW264.7细胞具有很强的黏附和吞噬抗原的能力,是研究微生物学、免疫学的常用细胞株.很多研究者发现这种细胞形态极不稳定,细胞状态的评价也很困难.本文作者结合RAW264.7培养经历及文献资料探讨RAW264.7细胞培养的经验教训和评价细胞状态的方法,旨在为培养该细胞的科研工作者提供一定的借鉴.