Vision in our three-dimensional world

Many aspects of our perceptual experience are dominated by the fact that our two eyes point forward. Whilst the location of our eyes leaves the environment behind our head inaccessible to vision, co-ordinated use of our two eyes gives us direct access to the three-dimensional structure of the scene in front of us, through the mechanism of stereoscopic vision. Scientific understanding of the different brain regions involved in stereoscopic vision and three-dimensional spatial cognition is changing rapidly, with consequent influences on fields as diverse as clinical practice in ophthalmology and the technology of virtual reality devices.This article is part of the themed issue ‘Vision in our three-dimensional world’.     

Response to “Critical Assessment of the Evidence for Striped Nanoparticles”

Stirling et al., (10.1371/journal.pone.0108482) presented an analysis on some of our publications on the formation of stripe-like domains on mixed-ligand coated gold nanoparticles. The authors shed doubts on some of our results however no valid argument is provided against what we have shown since our first publication: scanning tunneling microscopy (STM) images of striped nanoparticles show stripe-like domains that are independent of imaging parameters and in particular of imaging speed. We have consistently ruled out the presence of artifacts by comparing sets of images acquired at different tip speeds, finding invariance of the stipe-like domains. Stirling and co-workers incorrectly analyzed this key control, using a different microscope and imaging conditions that do not compare to ours. We show here data proving that our approach is rigorous. Furthermore, we never solely relied on image analysis to draw our conclusions; we have always used the chemical nature of the particles to assess the veracity of our images. Stirling et al. do not provide any justification for the spacing of the features that we find on nanoparticles: ~1 nm for mixed ligand particles and ~ 0.5 nm for homoligand particles. Hence our two central arguments remain unmodified: independence from imaging parameters and dependence on ligand shell chemical composition. The paper report observations on our STM images; none is a sufficient condition to prove that our images are artifacts. We thoroughly addressed issues related to STM artifacts throughout our microscopy work. Stirling et al. provide guidelines for what they consider good STM images of nanoparticles, such images are indeed present in our literature. They conclude that the evidences we provided to date are insufficient, this is a departure from one of the authors’ previous article which concluded that our images were composed of artifacts. Given that four independent laboratories have reproduced our measurements and that no scientifically rigorous argument is presented to invalidate our STM images, and also given that Stirling et al. do not contest the quality of our recent STM images, we re-affirm that specific binary mixture of ligands spontaneously form features in their ligand shell that we describe as stripe-like domains ~1 nm in width.     

Autonomy reconfigured: incorporating the role of the unconscious

The principle of respect for autonomy has served as a pillar of American bioethics. Through its application in response to physician paternalism and as the basis for informed consent, it has attained preeminent status in the discipline. New challenges in health care warrant a re-examination of the origins of our autonomy. Developmental psychology, cognitive neuroscience, and behavioral neurology all emphasize the intimate relationship between our cognitive and emotional development, and through this, our conscious and unconscious minds. Our intellectual, and particularly our moral development, are instilled in us by our moral mentors, and consequently by our community as a whole. Autonomy and community are therefore inextricably interlinked, and our emphasis on liberty, rights, and privacy without the inclusion of family, community, and social responsibility is biologically unsound. Appreciation of this reality should lead to a more balanced set of bioethical norms.     

Roles of stromal microenvironment in colon cancer progression

Although our understanding of epithelial cancer cells has advanced significantly, our understanding of the cancer microenvironment is still fragmentary. In contrast to our intuitive impression that our body always suppresses cancer growth, recent pieces of evidence show that cancer often exploits our body reactions to expand, invade local tissues and metastasize to distant organs. Accordingly, investigations of such body reactions in the tumour microenvironment should help us to design novel therapeutic strategies that can be combined with the traditional therapeutics targeted at the cancer cells themselves. In this article, I am going to review our recent efforts in search of novel therapeutic strategies against colon cancer using mouse models.     

Setting the Record Straight on Data Supporting Postnatal Oogenesis in Female Mammals

Of all the ‘certainties’ in mammalian female reproductive biology, the concept that a non-renewing oocyte reserve is set forth in the ovaries at birth may be the most longstanding and widely held. However, when data from our studies of oocyte apoptosis unintentionally began to contradict this theory in the latter part of 2002, we embarked on an investigation, unbiased by any pre-conceived dogmas, to determine if oocyte production persists in adult female mice. In 2004, we presented our first experimental findings in the journal Nature, which indicated that oogenesis indeed continues in adulthood. Amidst widespread skepticism, we moved forward with our studies and this year published our follow-up experiments in the journal Cell. Results from this latter body of work not only reinforced our earlier conclusions but also identified bone marrow as a surprising source of oocyte-producing germ cells in adults. Although this study has also been met with skepticism, doubts raised in commentaries on our work are largely based on inaccurate or incomplete assessments of our experimental models and results. Here we have attempted to clarify published misperceptions and misinterpretations of our data, and offer additional insights that challenge the idea of fixed endowment of oocytes at birth.     

The dynamic microbiome

While our genomes are essentially static, our microbiomes are inherently dynamic. The microbial communities we harbor in our bodies change throughout our lives due to many factors, including maturation during childhood, alterations in our diets, travel, illnesses, and medical treatments. Moreover, there is mounting evidence that our microbiomes change us, by promoting health through their beneficial actions or by increasing our susceptibility to diseases through a process termed dysbiosis. Recent technological advances are enabling unprecedentedly detailed studies of the dynamics of the microbiota in animal models and human populations. This review will highlight key areas of investigation in the field, including establishment of the microbiota during early childhood, temporal variability of the microbiome in healthy adults, responses of the microbiota to intentional perturbations such as antibiotics and dietary changes, and prospective analyses linking changes in the microbiota to host disease status. Given the importance of computational methods in the field, this review will also discuss issues and pitfalls in the analysis of microbiome time-series data, and explore several promising new directions for mathematical model and algorithm development.     

NHJ direct online in January 2011!

In one of our previous Editor’s pages, we announced that our Netherlands Heart Journal (NHJ) received a 2009 impact factor of 1.4, which is a crucial step for our journal. This achievement was a consequence of another important step for our journal, being the recognition by PubMed as of January 2007. From that moment on, the Chief Editorial Board and our Publisher observed a considerable increase in submitted articles. In 2007 we received a total of 62 submissions.     

Twenty years of Alzheimer's disease-causing mutations

In this study, we review our finding of APP mutations in Alzheimer's disease in 1990-1991 with the benefit of 20 years' perspective. We discuss the historical context in which we made the finding, its immediate and continuing effects on research activity and our hopes for successful clinical testing of the hypothesis. We also briefly discuss the effects finding APP mutations has had on our own careers and those of our colleagues from 1991.     

A craniometric study of the C. de Lange syndrome (CdLS)

After a short review of our method, we compared the results of the radiographs of 18 cases of CdLS to the results of our normal material. All of our normal statistical data was obtained from AP and lateral view radiographs at a distance of 1 m, in the prevailing conditions of everyday practice in a radiological department. We studied quantitative changes such as microcephaly and brachycephaly, and for the first time we introduced qualitative changes such as occipital rotation and the study of obliquity of the foramen magnum (line BAO). We found microcephaly in all our cases of CdLS and brachycephaly in only 72%. Furthermore, we found a lack of positive occipital rotation in all our cases of CdLS and the line BAO turned posteriorly with O higher than BA. The same conditions were observed on our normal material only in an early postnatal stage.     

Open science and meta‐analysis allow for rapid advances in ecology: A response to Menegotto et al. (2019)

Menegotto and colleagues’ (2019) commentary on our paper (Kinlock et al., 2018) does not negate our findings, but by recategorizing and reanalysing a portion of our data set, advances our knowledge of the latitudinal diversity gradients (LDGs) in marine ecosystems, particularly emphasizing different findings for benthic LDGs as a result of the recategorization of the data. Furthermore, we see the contribution by Menegotto et al. (2019) as highlighting the importance of scientific transparency; we believe that this insight into the nature of LDGs in marine systems would have been delayed, if not unobtainable, had we not provided fully transparent methods and complete data in our paper.     

Experimentalist Meets Theoretician: A Tale of Two Scientific Cultures

This is the story of how a small team of experimentalists and theoreticians collaborated to develop a theoretical model for vesicle formation during endocytosis. In telling our story, we hope to distil some general conclusions about the purpose and value of theoretical models and how best to navigate collaborations between experimentalists and theoreticians. We encountered challenges in building and publishing our model, but through our experiences we gained insight into how such collaborations can be profitably conducted. We also developed opinions about how theoretical models should be evaluated by peer reviewers and editors. During the evolution of our theoretical model, we educated each other, organized our thoughts and our data, developed a conceptual framework for understanding the mechanochemistry of endocytosis, and generated testable hypotheses that stimulated new experiments.     

Simultaneous and selective inference: Current successes and future challenges

The previous decade can be viewed as a second golden for era Multiple Comparisons research. I argue that much of the success stems from our being able to address real current needs. At the same time, this success generated a plethora of concepts for error rate and power, as well as multiplicity of methods for addressing them. These confuse the users of our methodology and pose a threat. To avoid the threat, it is our responsibility to match our theoretical goals to the goals of the users of statistics. Only then should we match the methods to the theoretical goals. Considerations related to such needs are discussed: simultaneous inference or selective inference, testing or estimation, decision making or scientific reporting. I then further argue that the vitality of our field in the future - as a research area - depends upon our ability to continue and address the real needs of statistical analyses in current problems. Two application areas offering new challenges have received less attention in our community to date are discussed. Safety analysis in clinical trials, where I offer an aggregated safety assessment methodology and functional Magnetic Resonance Imaging.     

Making our diabetes patients' office visits more productive

Improving our health care procedures is ideally a collaborative and ongoing process, yet it takes time we may not feel we can easily afford. If we can consider how we might make even one change to improve our procedures, we might also be able to help improve not only the capabilities and skills of each member of our health care teams but also the ability of our patients to engage in effective diabetes self-care.     

The role of metacognition in human social interactions

Metacognition concerns the processes by which we monitor and control our own cognitive processes. It can also be applied to others, in which case it is known as mentalizing. Both kinds of metacognition have implicit and explicit forms, where implicit means automatic and without awareness. Implicit metacognition enables us to adopt a we-mode, through which we automatically take account of the knowledge and intentions of others. Adoption of this mode enhances joint action. Explicit metacognition enables us to reflect on and justify our behaviour to others. However, access to the underlying processes is very limited for both self and others and our reports on our own and others' intentions can be very inaccurate. On the other hand, recent experiments have shown that, through discussions of our perceptual experiences with others, we can detect sensory signals more accurately, even in the absence of objective feedback. Through our willingness to discuss with others the reasons for our actions and perceptions, we overcome our lack of direct access to the underlying cognitive processes. This creates the potential for us to build more accurate accounts of the world and of ourselves. I suggest, therefore, that explicit metacognition is a uniquely human ability that has evolved through its enhancement of collaborative decision-making.     

Building a path in cell biology

Setting up a new lab is an exciting but challenging prospect. We discuss our experiences in finding a path to tackle some of the key current questions in cell biology and the hurdles that we have encountered along the way.We were both fortunate to receive the ASCB Early Career Life Scientist Award this year and were offered this opportunity to discuss our science and experiences. As we are at very similar stages in our careers (Iain has had a lab for 5 years, and Gia has had a lab for 6 years), we decided to compare our experiences starting our labs and conducting science and to discuss the decisions that we have made along the way.     

Root effect hemoglobins

The Root effect describes an extreme pH sensitivity expressed in the hemoglobins of certain fish, in which it plays a unique physiological role. This review describes our general understanding of the effect of protons on the oxygen binding properties of hemoglobin and the particular properties which characterize Root effect proteins. The development of our understanding of the molecular origins of this effect is outlined and the role played by our ever expanding knowledge of protein structure is highlighted. The present state of our knowledge is detailed.     

The Future of Anthropology

The future of anthropology depends on what it contributes, both to thought and to society. Whether it survives, flourishes, or becomes extinct depends on anthropology's ability to become an intregal and significant, yet not subservient, part of our culture and society. To flourish, we must press outward; we must mobilize our work and ourselves to make a difference beyond the discipline and the academy. This objective implies change in our priorities and hence in our work.     

Planet of the apes

What makes us humans so special? Our language, our genes, our culture, our cognitive skills? At the Max-Planck-Institute for Evolutionary Anthropology in Leipzig, psychologists, linguists and biologists tackle this old question in a truly multidisciplinary way. Their results have implications not just for our understanding of human evolution – they also touch directly on many social and environmental issues. Florian Maderspacher reports.     

Going Organic: Converting Patagonia's Cotton Product Line

The integration of industrial ecology principles into a business may mean significant changes in its customary activities. In this article, we present a case study of a decision by Patagonia, a manufacturer and distributor of clothing and gear for outdoor sports, to use only organically grown cotton for our cotton products as of spring I996.We describe the history of our efforts to reduce our environmental impacts, the relationship between understanding the life-cycle impacts of garments in general and cotton in particular onour decision, and the changes required throughout the company to implement the decision. Although initial salesof the organic cotton products have met or exceeded expectations, most customers continue to buy our productsfor traditional reasons: quality, fit, styling, and brand. Westruggle to change consumer perceptions about the environmental significance of their purchases and influencemajor apparel manufacturers to make a similar switch. Our experience suggests, first, that consumers and industryneed to understand the principles of industrial ecology and, second, that environmental improvements must be integrated into all aspects of operations (e.g., marketing). Anunexpected benefit of the decision was an increase in our knowledge about the garment life cycle, which in turn improves our ability to develop new fabrics when off-the-shelf products do not meet our needs. Much remains to bedone, howevel; to reduce impacts associated with other aspects Of our products and corporate activities.     

A radiotelemetry system for polysomnographic recordings in lambs

The use of telemetry in biomedical research is rapidly increasing and is soon likely to be standard in research fields where prolonged recordings of multiple physiologic variables are necessary in freely moving animals. We describe our experience with a radiotelemetry system designed in our laboratory for polysomnographic recordings in newborn lambs. The system comprises eight channels: four channels for electromyographic activity of respiratory muscles, and one channel each for electrocorticogram, eye movement, electrocardiogram, and nasal flow. Using this system, we report our experience on the study of respiration and spontaneous apneas in the various states of consciousness, based on more than 500 h of recordings. Addition of radiotelemetry to our armamentarium has proven to be of invaluable help for the study of neonatal apneas and has now become routine in our laboratory.