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)

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)

Mouse tracking, a new action‐based measure of behavior, has advanced theories of decision making with the notion that cognitive and social decision making is fundamentally dynamic. Implicit in this theory is that people's decision strategies, such as discounting delayed rewards, are stable over task design and that mouse trajectory features correspond to specific segments of decision making. By applying the hierarchical drift diffusion model and the Bayesian delay discounting model, we tested these assumptions. Specifically, we investigated the extent (...) to which the “mouse‐tracking” design of decision‐making tasks (delay discounting task, DDT and stop‐signal task, SST) deviate from the standard “keypress” design of decision making tasks. We found remarkable agreement in delay discounting rates (intertemporal impatience) obtained in the keypress and mouse‐tracking versions of DDT (ρ = 0.90) even though these tasks were given about 1 week apart. Rates of evidence accumulation converged well in the two versions (DDT, ρ =.86; SST, ρ =.55). Omission/commission error in SST showed high agreement (ρ =.42, ρ =.53). Mouse‐motion features such as maximum velocity and AUC (area under the curve) correlated well with nondecision time (ρ = −.42) and boundary separation (ρ =.44)—the amount of information needed to accumulate prior to making a response. These results indicate that the response time (RT) and motion‐based decision tasks converge well at a fundamental level, and that mouse‐tracking features such as AUC and maximum velocity do indicate the degree of decision conflict and impulsivity. (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)

Building on the work of Schimmerling [Coherent sequences and threads, Adv. Math.216 89–117] and Steel [PFA implies AD L, J. Symbolic Logic70 1255–1296], we show that the failure of square principle at a singular strong limit cardinal implies that there is a nontame mouse. The proof presented is the first inductive step beyond L of the core model induction that is aimed at getting a model of ADℝ + "Θ is regular" from the failure of square at a singular (...) strong limit cardinal or PFA. (shrink)

Since intelligent design (ID) advocates claimed the ubiquitous mouse trap as an example of systems that cannot have evolved, mouse trap history is doubly relevant to studying material culture. On the one hand, debunking ID claims about mouse traps and, by implication, also about other irreducibly complex systems has a high educational value. On the other hand, a case study of mouse trap history may contribute insights to the academic discussion about material culture evolution. Michael Behe (...) argued that mouse traps cannot trap mice with any part missing; therefore, they cannot have a precursor with one part less, therefore, cannot have a continuous history, and therefore, cannot have evolved. The patented and seminal precursor of current flat snap traps, however, had one part less, because spring and striker were formed of one wire. Secondly, historical records that reach back into the Bronze Age suggest that its history continued for a very long time. Thirdly, all prerequisites for evolution (variation, transmission, and selection) abound in mouse trap populations. Hence, Behe’s triple-jump conclusion about mouse traps is false each step. There is no, in principle, impossibility for mouse traps to evolve. An evolutionary account of mouse trap history also has academic merits beyond its educational value. Three important conclusions can be drawn: (1) reticulate phylogenies of artifact systems may be resolvable as overlapping, but branching, phylogenies of parts; (2) homologous ideas may be realized by analogous material, that is, phylogenies of information do not necessarily coincide with those of material parts; (3) recombination of parts between different artifact systems increases the cumulative nature of cultural evolution. (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)

In this paper we explore a connection between descriptive set theory and inner model theory. From descriptive set theory, we will take a countable, definable set of reals, A. We will then show that , where is a canonical model from inner model theory. In technical terms, is a “mouse”. Consequently, we say that A is a mouse set. For a concrete example of the type of set A we are working with, let ODnω1 be the set of (...) reals which are ∑n definable over the model Lω1 , from an ordinal parameter. In this paper we will show that for all n 1, ODnω1 is a mouse set. Our work extends some similar results due to D.A. Martin, J.R. Steel, and H. Woodin. Several interesting questions in this area remain open. (shrink)

It is generally assumed that the developmental program of embryogenesis relies on epigenetic mechanisms. However, a mechanistic link between epigenetic marks and cell fate decisions had not been established so far. In a recent article, Torres‐Padilla and colleagues1 show that epigenetic information and, more precisely, histone arginine methylation mediated by CARM1 could contribute to cell fate decisions in the mouse 4‐cell‐stage embryo. It provides the first indications that global epigenetic information influences allocation of pluripotent cells toward the first cell (...) lineages. BioEssays 29:520–524, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

Six essential genes located near the mouse albino locus have been identified as required during specific periods of development. Amongst these six, each is required either during the preimplantation stages of development, at specific times during gastrulation, within 12 hrs after birth or during juvenile development. These genes were identified as a result of extensive genetic complementation analysis using embryos homozygous for the albino deletions. Although, in principal, the associated developmental abnormalities could result from loss of multiple genes, the (...) deletion phenotype in one case is identical to that induced by chemical mutagenesis. These results indicate that the abnormalities observed in deletion homozygotes may result from single gene loss. The deletions have proven useful not only as genetic tools to localize the position of the genes, but also as molecular entry points to the regions containing these genes. The current methodology being used to isolate candidate genes from the albino region is also reviewed here. (shrink)

Cet article se penche sur une figure de l’imaginaire collectif, à savoir Mickey Mouse. Cette souris sympathique qui a fait le tour du globe dans les années 1930 est devenue l’animal héraldique du triomphe des économies pulsionnelles et d’une mercantilisation du rêve de bonheur. En partant d’une réflexion sur la contiguïté entre l’activité ludique et l’art de l’animation, l’article tente d’aborder la question de « l’esthétisation de la politique » par le biais du jeu. Une référence constante à la (...) fonction du conte dans le monde enfantin nous permet d’articuler quelques enjeux de ce que W. Benjamin analyse, dans son essai sur L’Œuvre d’art à l’époque de sa reproductibilité technique, sous le terme de « seconde technique ». (shrink)

We identify a particular mouse, [Formula: see text], the minimal ladder mouse, that sits in the mouse order just past [Formula: see text] for all [Formula: see text], and we show that [Formula: see text], the set of reals that are [Formula: see text] in a countable ordinal. Thus [Formula: see text] is a mouse set. This is analogous to the fact that [Formula: see text] where [Formula: see text] is the sharp for the minimal inner (...) model with a Woodin cardinal, and [Formula: see text] is the set of reals that are [Formula: see text] in a countable ordinal. More generally [Formula: see text]. The mouse [Formula: see text] and the set [Formula: see text] compose the next natural pair to consider in this series of results. Thus we are proving the mouse set theorem just past projective. Some of this is not new. [Formula: see text] was known in the 1990s. But [Formula: see text] was open until Woodin found a proof in 2018. The main goal of this paper is to give Woodin’s proof. (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)

The present article explores the views of al-Jāḥiẓ, Abū Bakr al-Rāzī, and Fakhr al-Dīn al-Rāzī - three pre-modern thinkers of the Islamic world outside the Peripatetic tradition - on the question o...

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)

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)

Mouse vs. Cat in Chinese Literature: Tales and Commentary. Translated and introduced by Wilt l. Idema. Seattle: University of Washington Press, 2019. Pp. xvii + 254. $30.

Researchers have argued that bilingual speakers experience less emotion in their second language. However, some studies have failed to find differences in emotionality between first and second lang...

Affective computing research has advanced emotion recognition systems using facial expressions, voices, gaits, and physiological signals, yet these methods are often impractical. This study integrates mouse cursor motion analysis into affective computing and investigates the idea that movements of the computer cursor can provide information about emotion of the computer user. We extracted 16–26 trajectory features during a choice-reaching task and examined the link between emotion and cursor motions. Participants were induced for positive or negative emotions by music, film (...) clips, or emotional pictures, and they indicated their emotions with questionnaires. Our 10-fold cross-validation analysis shows that statistical models formed from “known” participants could predict nearly 10%–20% of the variance of positive affect and attentiveness ratings of “unknown” participants, suggesting that cursor movement patterns such as the area under curve and direction change help infer emotions of computer users. (shrink)

John Searle’s Chinese Room Argument purports to demonstrate that syntax is not sufficient for semantics, and, hence, because computation cannot yield understanding, the computational theory of mind, which equates the mind to an information processing system based on formal computations, fails. In this paper, we use the CRA, and the debate that emerged from it, to develop a philosophical critique of recent advances in robotics and neuroscience. We describe results from a body of work that contributes to blurring the divide (...) between biological and artificial systems; so-called animats, autonomous robots that are controlled by biological neural tissue and what may be described as remote-controlled rodents, living animals endowed with augmented abilities provided by external controllers. We argue that, even though at first sight, these chimeric systems may seem to escape the CRA, on closer analysis, they do not. We conclude by discussing the role of the body–brain dynamics in the processes that give rise to genuine understanding of the world, in line with recent proposals from enactive cognitive science. (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)

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)

SETI scientists have done this by looking for the equivalent of television signals that might emanate from the planet of a civilization that uses radio-wave broadcasts as we do. They have found no evidence of the equivalent of our radio/TV signals in our galactic neighborhood, but that result is inconclusive. Galactic civilizations may be so different or so far ahead of us that they don't use radio waves to communicate. Or perhaps it's just that TV-watching is incompatible with advanced intelligence.

Expression patterns of Antennapedia‐like homeogenes in the mouse embryo show many similarities to those of their homologues in Drosophila. It is argued here that homeogenes may regulate development of the body plan in mouse by mechanisms similar to those used in Drosophila. In particular, they may differentially specify positional address of cell groups within lineage compartments along the body axes. In vertebrates, a single ancestral homeogene cluster has become duplicated to give four separate clusters. Comparisons of homeogene expression (...) patterns between different clusters of the mouse suggest ways in which duplication has permitted development of a more complex body plan. Cluster duplication may therefore have provided a selective advantage during vertebrate evolution. (shrink)

Rattus norvegicus is an important experimental organism and interesting to evolutionary biologists. The recently published draft rat genome sequence1 provides us with insights into both the rat's evolution and its physiology. We learn more about genome evolution and, in particular, the adaptive significance of gene family expansions and the evolution of rodent genomes, which appears to have decelerated since the divergence of mouse and rat. An important observation is that some regions of genomes, many in noncoding regions, show very (...) high sequence conservation, while others show unexpectedly fast evolution. Both of these may be pointers to functional significance. BioEssays 26:1039–1042, 2004. © 2004 Wiley Periodicals, Inc. (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)

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)

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)

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)