When Mrs. Frederick C. Little's second son was born, everybody noticed that he was not much bigger than a mouse. (E. B. White, 1945, 1.) In every somatic and morphological detail Stuart Little was...

The discussion by Greely et al. (2007) of the Stanford advisory committee's deliberations regarding whether to pursue research involving the transfer of human brain stem cells to fetal mice not onl...

Human–nonhuman chimeras have been the focus of ethical controversies for more than a decade, yet some related issues remain unaddressed. For example, little has been said about the relationship between the origin of transferred cells and the morally relevant capacities to which they may give rise. Consider, for example, a developing mouse fetus that receives a brain stem cell transplant from a human and another that receives a brain stem cell transplant from a dolphin. If both chimeras (...) acquire morally relevant capacities as a result of transplantation, and if those capacities are indistinguishable, should the difference in cell origin matter to how we classify these creatures? I argue that if morally relevant capacities are easy to detect, cell origin is irrelevant to how the chimera ought to be treated. However, if such capacities are hard to detect, cell origin should play a role in considerations about how to treat the chimera. (shrink)

I am grateful to the authors who commented on my article (Piotrowska 2014) for their careful examination of my argument. They have presented a variety of stimulating ideas and suggestions, with which I largely agree and which I would like to discuss further, but in the interest of brevity, I shall try to concentrate only on points of contention.

Consideration of the amazing organized intricacy of human cortical anatomy entails a deeper appreciation of nature that is fully consistent with a mature religious spirit. A brain seems at first glance to be a mere lump of grayish claylike stuff, but facts of basic neuroanatomy compel us to consider that this particular kind of stuff may really contain all the richly tangible and richly ghostly inner essences of emotion, thought, and behavior. Humans are the “college graduates” of evolution. The (...) human cortex is 3,400 times the volume of, yet only slightly thicker (about 3 millimeters) than, that of the mouse. This remarkable sheet is as thin as a graduation‐day “mortarboard” cap, but its 2,600 square centimeter area is four times as large (about 20 × 20 inches if a square; both metric and English units used deliberately). Zooming in, there are about 50 billion cortical neurons; though named after “pyramids,” they are more like tiny “magic trees,” with branches and roots so long and fine that there are 1 or 2 miles of these electrically scintillating fibers within each cubic millimeter of cortex. Cortical neurons communicate intimately: viewed from above, beneath a single square millimeter 100,000 nerve cells intertwine; each such neuron makes 5,000 or more connections with others. These and many additional amazing facts about brain tissue, together with some conjectures about dense connectedness in the mathematics of graph theory, help to bear out the groundwork prepared by such pioneers as Ralph Wendell Burhoe that the spirit and knowledge of science might rejoin that of religion. If it takes enchanted matter to contain consciousness, this is a kind of enchantment that science may well be able to penetrate for eventual thoroughgoing understanding. Inevitable by‐products will be greater reverence for nature and greater awe at the mystery of nature's origin. (shrink)

The power of the application of bioinformatics across multiple publicly available transcriptomic data sets was explored. Using 19 human and mouse circadian transcriptomic data sets, we found that NR1D1 and NR1D2 which encode heme‐responsive nuclear receptors are the most rhythmic transcripts across sleep conditions and tissues suggesting that they are at the core of circadian rhythm generation. Analyzes of human transcriptomic data show that a core set of transcripts related to processes including immune function, glucocorticoid signalling, and (...) lipid metabolism is rhythmically expressed independently of the sleep‐wake cycle. We also identify key transcripts associated with transcription and translation that are disrupted by sleep manipulations, and through network analysis identify putative mechanisms underlying the adverse health outcomes associated with sleep disruption, such as diabetes and cancer. Comparative bioinformatics applied to existing and future data sets will be a powerful tool for the identification of core circadian‐ and sleep‐dependent molecules. (shrink)

This article postulates a method of determining the date of human settlement in the Canary Islands by establishing when species of mice, which are commensal with human beings and hence in all likelihood migrated with them, arrived in the archipelago. At the same time, the extinction of several species of endemic rodents may also correlate with such arrivals. The study establishes the outer limits for the arrival of the mouse species, between the 5th millennium BCE and the (...) 15th century CE, but, while indicative archaeological evidence indicates human settlement was established by around the middle of the 1st millennium BCE, the absence of conclusive dating of fossil mice remains leaves a definitive conclusion for the start of such settlement still open. (shrink)

Well-documented differences in the psychology and behavior of men and women have spurred extensive exploration of gender's role within the brain, particularly regarding emotional processing. While neuroanatomical studies clearly show differences between the sexes, the functional effects of these differences are less understood. Neuroimaging studies have shown inconsistent locations and magnitudes of gender differences in brain hemodynamic responses to emotion. To better understand the neurophysiology of these gender differences, we analyzed recordings of single neuron activity in the human (...) brain as subjects of both genders viewed emotional expressions. This study included recordings of single-neuron activity of 14 (6 male) epileptic patients in four brain areas: amygdala (236 neurons), hippocampus ( n = 270), anterior cingulate cortex ( n = 256), and ventromedial prefrontal cortex ( n = 174). Neural activity was recorded while participants viewed a series of avatar male faces portraying positive, negative or neutral expressions. Significant gender differences were found in the left amygdala, where 23% ( n = 15∕66) of neurons in men were significantly affected by facial emotion, vs. 8% ( n = 6∕76) of neurons in women. A Fisher's exact test comparing the two ratios found a highly significant difference between the two ( p. (shrink)

Mouse models of human genetic disorders provide a valuable resource for investigating the pathogenesis of genetic disease and for testing potential therapies. The high degree of resolution of linkage mapping in the mouse allows mutant phenotypes to be mapped precisely which, combined with the accurate definition of areas of homology between the mouse and human genomes, greatly facilitates the identification of mouse models. We describe here mouse models of human single gene disorders (...) dividing them into three categories depending on the information available; phenotypic similarities, comparative mapping and identification of the underlying genetic lesion. (shrink)

Patient-derived xenografts are currently promoted as new translational models in precision oncology. PDXs are immunodeficient mice with human tumors that are used as surrogate models to represent specific types of cancer. By accounting for the genetic heterogeneity of cancer tumors, PDXs are hoped to provide more clinically relevant results in preclinical research. Further, in the function of so-called “mouse avatars”, PDXs are hoped to allow for patient-specific drug testing in real-time. This paper examines the circulation of knowledge and (...) bodily material across the species boundary of human and personalized mouse model, historically as well as in contemporary practices. PDXs raise interesting questions about the relation between animal model and human patient, and about the capacity of hybrid or interspecies models to close existing translational gaps. We highlight that the translational potential of PDXs not only depends on representational matching of model and target, but also on temporal alignment between model development and practical uses. Aside from the importance of ensuring temporal stability of human tumors in a murine body, the mouse avatar concept rests on the possibility of aligning the temporal horizons of the clinic and the lab. We examine strategies to address temporal challenges, including cryopreservation and biobanking, as well as attempts to speed up translation through modification and use of faster developing organisms. We discuss how featured model virtues change with precision oncology, and contend that temporality is a model feature that deserves more philosophical attention. (shrink)

There has always been great interest in animal models of human genetic disease, and mice provide the largest number of examples. A mutation in the homologous gene in mice does not always lead to the same phenotype as is found in man, however. Recent studies made it apparent that one mutation can have markedly different phenotypes when placed on different genetic backgrounds. This variation is due to different alleles at modifying loci in various inbred strains. Thus, if one wishes (...) to obtain the optimal mouse model for a human disease, one needs to choose the correct genetic background as well as the correct mutation. (shrink)

The rediscovery of the silver-backed chevrotain, an endemic species to Vietnam, in 2019, after almost 30 years of being lost to science, is a remarkable outcome for the global conservation agenda. However, along with the happiness, there is a tremendous concern for the conservation of the species as eating wildmeat, including chevrotain, is deeply rooted in the socio-cultural values of Vietnamese. Meanwhile, conservation plans face multiple obstacles since the species has not been listed in the list of endangered, precious, and (...) rare wildlife prioritized for protection and is still classified by the IUCN as lacking data. Given the limited effectiveness of conservation measures, this essay discusses the determining roles of local actions, community cooperation, and humanistic values oriented toward eco-surplus culture in addressing the global biodiversity conservation agenda, specifically the conservation of the silver-backed chevrotain. Local actions and community cooperation for conservation can be actualized to achieve conservation goals through citizen and community sciences, integration of modern technologies (e.g., Internet, crowdfunding platforms, social media, AI, etc.), and the bonding capability of humanistic values that prioritize environmental healing. Communicating conservation information to the community, especially the children, has to stimulate their thinking and imagination about nature, develop their curiosity and desire to protect wildlife, and eventually build eco-surplus core values in their mindsets. To successfully awaken the humanistic values within the community and incorporate them into conservation endeavors, the conservation message with the name “mouse-deer”, “chevrotain”, or scientific name (Tragulus versicolor) is largely insufficient as they show an unfamiliar feeling. Therefore, we suggest calling the mouse-deer “cheo cheo”, a local name that can create familiarity and closeness, awaken the environmental conscience and humanistic values, and stimulate thinking and imagination. All these factors are essential for conservationists, scientists, and the government to support the community in building the eco-surplus culture. (shrink)

This paper focuses on the change of the image of “mouse” which was transformed from the legend of Fifteen Strings of Cash to the other versions. The legend of Fifteen Strings of Cash, written by Zhu Suchen, was a story of the vindication of defendants in a court case and formed the basis for a series adaptations. The legend of Fifteen Strings of Cash provided a frame of imagination about the image of a “mouse”. Meanwhile, the adaptation of (...) the legend in folk opera provided a more ethical narrative than the original. The folk versions not only strengthened the “evil” of the “mouse”, but also heightened the suffering of innocent scholars. In the contemporary versions after 1949, the “mouse” as an animal disappeared in the story, and Lou Ashu became a pure villain in this play, which also symbolized “evil” and pointed to the feudal and backward old society. (shrink)

Neural tube defects are one of the commonest human birth defects, with more than 0.5% of some populations affected. Mouse models are being used in an attempt to identify genes that could be involved in these malformations. Only two mouse mutations are known to lead to craniorachischisis, failure of closure of almost the entire neural tube. Two recent papers report that the gene for one of these, Loop‐tail, has now been identified and sequenced.1, 2 It has been (...) given the designation Ltap/Lpp1 and appears to function in floor plate formation. It will be of great interest to investigate the role of this gene in human neural tube defects. BioEssays 24:580–583, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

This article explores the development of a novel biomedical research organism, and its potential to remake the species and spaces of translational medicine. The humanized mouse is a complex experimental object in which mice, rendered immunodeficient through genetic alteration, are engrafted with human stem cells in the hope of reconstituting a human immune system for biomedical research and drug testing. These chimeric organisms have yet to garner the same commentary from social scientists as other human–animal hybrid (...) forms. Yet, they are rapidly being positioned as central to translational medicine in immunological research and pharmaceutical development. This article explores the complex relations between species and spaces they seek to enact. Humanizing mice simultaneously moves these animal forms towards the intimate geographies of corporeal equivalence with humans and the expansive geographies of translational research. These multiple trajectories are achieved by the way humanized mice function as both uncertain ‘epistemic things’ and as expansive ‘collaborative things’, articulating mouse genetics with other research, notably stem cell science. In the context of post-genomics, their indeterminacy is critical to their collaborative value; their expansive potential follows as much from their biological openness as from specific expectations. Yet, these new research organisms have both accumulative and disruptive capacities, for there are patterns of interference between these trajectories, remaking boundaries between experimental practices and clinical contexts. (shrink)

In this review, we discuss the application of mouse models to the identification and pre‐clinical validation of novel therapeutic targets in colorectal cancer, and to the search for early disease biomarkers. Large‐scale genomic, transcriptomic and epigenomic profiling of colorectal carcinomas has led to the identification of many candidate genes whose direct contribution to tumourigenesis is yet to be defined; we discuss the utility of cross‐species comparative ‘omics‐based approaches to this problem. We highlight recent progress in modelling late‐stage disease using (...) mice, and discuss ways in which mouse models could better recapitulate the complexity of human cancers to tackle the problem of therapeutic resistance and recurrence after surgical resection. (shrink)

What is the biological basis for human cognition? Our understanding why human brains make us smarter than other animals is still in its infancy. In recent years, astrocytes have been shown to be indispensable for neuronal survival, growth, synapse formation, and synapse function. Now, in a new study from Maiken Nedergaard and Steven Goldman's groups (Han et al., 2013), human glia progenitor cells have been transplanted into mouse forebrains. These progenitors survived, migrated widely, and gave rise (...) to astrocytes that displayed the characteristics of human astrocytes in the rodent host brains. Strikingly, the mice with transplanted human cells displayed improved long term potentiation (LTP) and learning, suggesting the potential importance of human astrocytes in the unique cognitive abilities of human brains. This landmark paper is an important first step toward future investigations of whether and how human astrocytes play a role in distinguishing the cognitive abilities of humans from those of other animals. (shrink)

The largest transcriptome reported so far comprises 60,770 mouse full‐length cDNA clones, and is an effective reference data set for comparative transcriptomics. The number of mouse cDNAs identified greatly exceeds the number of genes predicted from the sequenced human and mouse genomes. This is largely because of extensive alternative splicing and the presence of many non‐coding RNAs (ncRNAs), which are difficult to predict from genomic sequences. Notably, ncRNAs are a major component of the transcriptomes of higher (...) organisms, and many sense–antisense pairs have been identified. The ncRNAs function in a range of regulatory mechanisms for gene expression and other biological processes. They might also have contributed to the increased functional diversification of genomes during evolution. In this review, we discuss aspects of the transcriptome of various organisms in relation to the mouse data, in order to shed light on the regulatory mechanisms and physiological significance of these abundant RNAs. BioEssays 26:833–843, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

Given the broad coverage of “Human Brain Surrogates Research: The Onrushing Ethical Dilemma,” this commentary focuses on the section “human/nonhuman brain chimeras,” and specifically, the questions...

One of the characteristics of all somatic cells is a finite life span. Cells may proliferate until they reach a point after which, although they are metabolically active, they can no longer produce daughter cells. This observation is central to the clonal exhaustion hypothesis, a mechanism cited to explain age-associated immune dysfunction. In this hypothesis, repeated division of lymphocytes leads to a replicative limit, after which they enter the senescent phase but are not lost from the pool of T cells. (...) Advancing age would then be associated with an increase in the number of T cells that are unable to proliferate to a stimulus which induces a proliferative response in T cells from younger individuals. This hypothesis seems both logical and reasonable and is supported by data from both humans and mice with the demonstration of an age-related accumulation of senescent T cells in both species. However, there is an apparent paradox. The paradox arises because the onset of immunosenescence appears to be more closely linked to the life span of the animal rather than the life span of the lymphocyte. BioEssays 21:519–524, 1999. © 1999 John Wiley & Sons, Inc. (shrink)

Recent research suggests that human memories are stored not between neurons as synaptic weights, but within individual neurons themselves. This opens the possibility to replace the dominant paradigm of brain function – neural networks – with a new one. In this article, I explore how “identified neurons” could explain how memories are stored, and how human traits are implemented in the brain.

Melatonin, the neuro‐hormone synthesized during the night, has recently seen an unexpected extension of its functional implications toward type 2 diabetes development, visual functions, sleep disturbances, and depression. Transgenic mouse models were instrumental for the establishment of the link between melatonin and these major human diseases. Most of the actions of melatonin are mediated by two types of G protein‐coupled receptors, named MT1 and MT2, which are expressed in many different organs and tissues. Understanding the pharmacology and function (...) of mouse MT1 and MT2 receptors, including MT1/MT2 heteromers, will be of crucial importance to evaluate the relevance of these mouse models for future therapeutic developments. This review will critically discuss these aspects, and give some perspectives including the generation of new mouse models. (shrink)

We focus on the thesis that action understanding is a function of the mirror neuron system. According to our opinion, understanding is a process that runs through hermeneutic circles from the “Vorverständnis” (“previous understanding”) to steps of deeper understanding. Our critique relates to the narrow neuroscientific definition of action understanding as the capacity to recognize several movements as belonging to one action. After a reconstruction of the model's developments, we will challenge the claims of the model by Rizzolatti and (...) Sinigaglia (2010). By analyzing the relation between the experimental results and its interpretation, we will conclude that there is no proof that mirror neuron activity leads to action understanding. (shrink)

Motion-sound synesthesia is characterized by illusory auditory sensations linked to the pattern and rhythms of motion of visually experienced but soundless object, like an optical flow array, a ball bouncing or a horse galloping. In an MRI study with a group of three synesthetes and a group of eighteen control participants, we found structural changes in the brains of synesthetes in the subcortical multisensory areas of the superior and inferior colliculi. In addition, functional magnetic resonance imaging data showed activity in (...) motion-sensitive regions, as well as temporal and occipital areas, and the cerebellum. However, the synesthetes had a higher activation within the left and right cuneus, with stronger activations when viewing optical flow stimuli. There was also a general difference in connectivity of the colliculi with the above mentioned regions between the two groups. These findings implicate low-level mechanisms within the human neuroaxis as a substrate for local connectivity and cross activity between perceptual processes that are “distant” in terms of cortical topography. The present findings underline the importance of considering the role of subcortical systems and their connectivity to multimodal regions of the cortex and they strengthen a parsimonious account of synesthesia, at the least of the visual-auditory type. (shrink)

activity” has been considered to play a major role in the short-term maintenance of memories. Many studies since then have provided support for this view and greatly advanced our knowledge of the effects of stimulus type and modality on delay activity and its temporal dynamics. In humans, working memory has also been a subject of intense investigation using scalp and intracranial electroencephalography as well as magnetoencephalography, which provide estimates of local population activity. The published findings include reports of systematic changes (...) in signal amplitude during working memory in the theta, alpha, beta. (shrink)

Cook et al. argue that mirror neurons originate from associative learning processes, without evolutionary influence from social-cognitive mechanisms. We disagree with this claim and present arguments based upon cross-species comparisons, EEG findings, and developmental neuroscience that the evolution of mirror neurons is most likely driven simultaneously and interactively by evolutionarily adaptive psychological mechanisms and lower-level biological mechanisms that support them.

Although mouse‐tracking has been taken as a real‐time window on different aspects of human decision‐making processes, whether purely semantic information affects response conflict at the level of motor output as measured through mouse movements is still unknown. Here, across two experiments, we investigated the effects of semantic knowledge by predicting participants’ performance in a standard keyboard task and in a mouse‐tracking task through distributional semantics, a usage‐based modeling approach to meaning. In Experiment 1, participants were shown (...) word pairs and were required to perform a two‐alternative forced choice task selecting either the more abstract or the more concrete word, using standard keyboard presses. In Experiment 2, participants performed the same task, yet this time response selection was achieved by moving the computer mouse. Results showed that the involvement of semantic components in the task at hand is observable using both standard reaction times (Experiment 1) as well as using indexes extracted from mouse trajectories (Experiment 2). In particular, mouse trajectories reflected the response conflict and its temporal evolution, with a larger deviation for increasing word semantic relatedness. These findings support the validity of mouse‐tracking as a method to detect deep and implicit decision‐making features. Additionally, by demonstrating that a usage‐based model of meaning can account for the different degrees of cognitive conflict associated with task achievement, these findings testify the impact of the human semantic memory on decision‐making processes. (shrink)

The mechanism by which humans perceive others differs greatly from how humans perceive inanimate objects. Unlike inanimate objects, humans have the distinct property of being “like me” in the eyes of the observer. This allows us to use the same systems that process knowledge about self-performed actions, self-conceived thoughts, and self-experienced emotions to understand actions, thoughts, and emotions in others. The authors propose that internal simulation mechanisms, such as the mirror neuron system, are necessary for normal development of recognition, (...) imitation, theory of mind, empathy, and language. Additionally, the authors suggest that dysfunctional simulation mechanisms may underlie the social and communicative deficits seen in individuals with autism spectrum disorders. (shrink)

It is now generally accepted that the motor system is not purely dedicated to the control of behavior, but also has cognitive functions. Mirror neurons have provided a new perspective on how sensory information regarding others’ actions and gestures is coupled with the internal cortical motor representation of them. This coupling allows an individual to enrich his interpretation of the social world through the activation of his own motor representations. Such mechanisms have been highly preserved in evolution as they are (...) present in humans, apes and monkeys. Recent neuroanatomical data showed that there are two different connectivity patterns in mirror neuron networks in the macaque: one is concerned with sensorimotor transformation in relation to reaching and hand grasping within the traditional parietal-premotor circuits; the second one is linked to the mouth/face motor control and the new data show that it is connected with limbic structures. The mouth mirror sector seems to be wired not only for ingestive behaviors but also for orofacial communicative gestures and vocalizations. Notably, the hand and mouth mirror networks partially overlap, suggesting the importance of hand-mouth synergies not only for sensorimotor transformation, but also for communicative purposes in order to better convey and control social signals. (shrink)

The study of eye movements is a common way to non-invasively understand and analyze human behavior. However, eye-tracking techniques are very hard to scale, and require expensive equipment and extensive expertise. In the context of web browsing, these issues could be overcome by studying the link between the eye and the computer mouse. Here, we propose new analysis methods, and a more advanced characterization of this link. To this end, we recorded the eye, mouse, and scroll movements (...) of 151 participants exploring 18 dynamic web pages while performing free viewing and visual search tasks for 20 s. The data revealed significant differences of eye, mouse, and scroll parameters over time which stabilize at the end of exploration. This suggests the existence of a task-independent relationship between eye, mouse, and scroll parameters, which are characterized by two distinct patterns: one common pattern for movement parameters and a second for dwelling/fixation parameters. Within these patterns, mouse and eye movements remained consistent with each other, while the scrolling behaved the opposite way. (shrink)

The largest proportion of microRNAs in humans (ca. 40–50%) originated in the phylogenetic grouping defined as primates. The dynamic evolution of this family of non‐coding RNA is further demonstrated by the presence of microRNA unique to the human species. Investigations into the role of microRNA in cancer have until recently mainly focused on the more ancient members of this RNA family that are widely conserved in the animal kingdom. As I describe in this review the evolutionary young lineage and (...) species‐specific microRNA could be important contributors to cancers, especially in particular organs in primates compared to more distantly‐related research models. Elucidating the biological significance of primate and human‐specific microRNA in cancer could have important implications for cancer research and the use of non‐primate animal models. (shrink)

The zona pellucida is an extracellular coat that surrounds mammalian eggs and early embryos. This insoluble matrix separates germ from somatic cells during folliculogenesis and plays critical roles during fertilization and early development. The mouse and human zona pellucida contain three glycoproteins (ZP1 or ZPB, ZP2, ZP3), the primary structures of which have been deduced by molecular cloning. Targeted mutagenesis of endogenous mouse genes and transgenesis with human homologues provide models to investigate the roles of individual (...) zona components. Collectively, the genetic data indicate that no single mouse zona pellucida protein is obligatory for taxon‐specific sperm binding and that two human proteins are not sufficient to support human sperm binding. An observed post‐fertilization persistence of mouse sperm binding to “humanized” zona pellucida correlates with uncleaved ZP2. These observations are consistent with a model for sperm binding in which the supramolecular structure of the zona pellucida necessary for sperm binding is modulated by the cleavage status of ZP2. BioEssays 26:29–38, 2004. Published 2003 Wiley Periodicals, Inc. (shrink)

The effects of calorie restriction have now been studied in two non‐human primates, the macaque Macaca mulatta and the mouse lemur Microcebus murinus. The study on lemurs and one of the two studies on macaques have reported a lifespan increase. In this review, I argue that these results are better explained by a lifespan decrease in the control group because of a bad diet and/or overfeeding, rather than by a real lifespan increase in calorie‐restricted animals. If these results (...) can be readily translated to humans, it would mean that no beneficial effect of calorie restriction on lifespan can be expected in normal‐weight or lean people, but that overweight and/or obese people could benefit to some extent from a decrease in excessive food intake. (shrink)

Mice with alterations to specific endogenous genes can be produced by gene targeting in embryonic stem cells. The field has developed rapidly over the past decade, so that large numbers of mice with different gene deficiencies have been generated. Knockout mice provide an ideal opportunity to analyse the function of individual mammalian genes and to model a range of human inherited disorders. This powerful approach has also identified numerous examples of gene redundancy and has highlighted the need to consider (...) metabolic differences between man and mouse in disease modelling. More sophisticated gene‐targeting methods are now being used to introduce subtle gene alterations. In the future, more refined genetic analysis and genome, rather than individual gene, alterations will be achieved by incorporating site‐specific recombination into targeting strategies. Gene targeting could also make a contribution to improved protocols for gene therapy. (shrink)

Ultraviolet (UV) radiation is a very common carcinogen in our environment, but epidemiological data on the relationship between skin cancers and ambient solar UV radiation are very restricted. In hairless mice the process of UV carcinogenesis can be studied in depth. Experiments with this animal model have yielded quantitative data on how tumor development depends on dose, time and wavelength of the UV radiation. In combination with epidemiological data, these experimental results can be transposed to humans. Comparative studies on molecular, (...) cellular and physiological changes in mouse and man can further our fundamental understanding of UV carcinogenesis in man. This is likely to improve risk assessments such as those related to a stratospheric ozone depletion, and to yield well‐targeted intervention schemes, e.g. prescribing a specific drug or diet, for high‐risk individuals. (shrink)

During development of the anterior eye segment, cells that originate from the surface epithelium or the neuroepithelium need to interact with mesenchymal cells, which predominantly originate from the neural crest. Failures of proper interaction result in a complex of developmental disorders such Peters' anomaly, Axenfeld–Rieger's syndrome or aniridia. Here we review the role of transcription factors that have been identified to be involved in the coordination of anterior eye development. Among these factors is PAX6, which is active in both epithelial (...) and mesenchymal cells during ocular development, albeit at different doses and times. We propose that PAX6 is a key element that synchronizes the complex interaction of cell types of different origin, which are all needed for proper morphogenesis of the anterior eye. We discuss several molecular mechanisms that might explain the effects of haploinsufficiency of PAX6 and other transcription factors, and the broad variation of the resulting phenotypes. BioEssays 26:374–386, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

This paper presents a computer model of cortical broadcast and competition based on spiking neurons and inspired by the hypothesis of a global neuronal workspace underlying conscious information processing in the human brain. In the model, the hypothesised workspace is realised by a collection of recurrently inter-connected regions capable of sustaining and disseminating a reverberating spatial pattern of activation. At the same time, the workspace remains susceptible to new patterns arriving from outlying cortical populations. Competition among these cortical populations (...) for influence on the workspace is effected by a combination of mutual inhibition and top-down amplification. (shrink)

We question the idea that the mirror neuron system is the substrate of social affordances perception, and we suggest that most of the activity seen in the parietal and premotor cortex of the human brain is independent of mirroring activity as characterized in macaques, but rather reflects a process of one's own action specification in response to social signals.

The concept of “information” is virtually ubiquitous in contemporary cognitive science. It is claimed to be “processed” (in cognitivist theories of perception and comprehension), “stored” (in cognitivist theories of memory and recognition), and otherwise manipulated and transformed by the human central nervous system. Fred Dretske's extensive philosophical defense of a theory of informational content (“semantic” information) based upon the Shannon-Weaver formal theory of information is subjected to critical scrutiny. A major difficulty is identified in Dretske's equivocations in the use (...) of the concept of a “signal” bearing informational content. Gibson's alternative conception of information (construed as analog by Dretske), while avoiding many of the problems located in the conventional use of “signal”, raises different but equally serious questions. It is proposed that, taken literally, the human CNS does not extract or process information at all; rather, whatever “information” is construed as locatable in the CNS is information only for an observer-theorist and only for certain purposes. (shrink)

Homeobox genes play essential roles in specifying the fates of different cell types during embryogenesis. In Drosophila, the homeotic gene caudal is important for the generation of posterior structures. In the mouse, the caudal homologue Cdx2 has been implicated in directing early processes in intestinal morphogenesis and in the maintenance of the differentiated phenotype. A recent study showed that Cdx2 null mutation was embryonically lethal, whereas Cdx2+/− mice developed multiple intestinal polyps in the proximal colon in addition to developmental (...) defects(1). There are striking phenotypic similarities and differences between Cdx2+/− and other mice predisposed to intestinal neoplasia. The possible role of Cdx2 in human colorectal tumorigenesis is discussed. (shrink)