The we gene is a modifier of the wal gene in mice

Interaction of gene wellhaarig (we) with genes waved alopecia (wal) and hairless (hr) was studied in mice. The mutant gene we is responsible for the development of a specific waved coat in homozygotes. Homozygous mice carrying mutant gene wal also have a wavy coat, though a partial alopecia develops with time in these animals. In homozygotes for the hr gene, hair loss is observed beginning from the age of ten days. A series of crosses we/we and wal/wal yielded animals with we/+wal/wal and we/we wal/wal genotypes. In mice we/+wal/wal carrying gene we at a single dose, alopecia is accelerated significantly as compared to the single-dose homozygotes +/+wal/wal. In we/we wal/wal mice, alopecia starts earlier than in we/+wal/wal mice; by the age of one month, the double homozygotes are almost hairless except for small body areas covered with a sparse coat. In addition, curliness of the first-generation hair in mice we/we wal/wal is much more expressed than in +/+wal/wal and we/we+/+ mice. The obtained evidence suggests that the we gene is a modifier of the wal gene because the former enhances the effects of the wal gene, which is confirmed by the earlier onset of alopecia and progression of the latter in mice having the we/+wal/wal genotype and especially in we/we wal/wal animals. The we/we hr/+ mice do not differ in coat from we/we+/+ mice; in both cases, the coat is wavy. The coat of double homozygotes we/we hr/hr, is similar to that of we/we+/+ mice until ten days of age, when the signs of alopecia appear. By the age of 21 days, mice we/we hr/hr have lost their coat completely like mice +/+ hr/hr. Hence, the we gene is a modifier of the wal gene though it does not interact with hr gene during the coat formation.     

On the epistemology of mental illness.

The most important epistemological problem in psychiatry is the detection of malingering. This is a consequence of the fact that there is no objective way to confirm any psychiatric diagnosis. Psychiatric diagnosis is based on subjective complaints. The discovery of objective markers for psychiatric diagnosis is problematic because it presupposes we can tell valid from faked subjective symptoms. But this is the difficulty. If we use pervasive irrationality as a sign of mental illness, we encounter the problem of identifying pervasive irrationality. To understand someone's behaviour, we have to assume it is largely rational. This precludes us from using behaviour to separate genuine from faked mental illness. There are a number of strategies used to solve any epistemological problem, and the most successful is the hypothetico-deductive method. If we use this, we can solve our epistemological problem. Genuine mental illness can be identified when it is the best explanation of the person's overall behaviour. Consilience of inductions is critical in supporting the validity of such explanations. This implies that it is merely a hypothesis that mental illness exists, and that we might discover that many mental illnesses, perhaps all, do not exist. We must embrace this possibility--only if we take a risk will we gain any knowledge.     

Explorations in statistics: permutation methods

Learning about statistics is a lot like learning about science: the learning is more meaningful if you can actively explore. This eighth installment of Explorations in Statistics explores permutation methods, empiric procedures we can use to assess an experimental result-to test a null hypothesis-when we are reluctant to trust statistical theory alone. Permutation methods operate on the observations-the data-we get from an experiment. A permutation procedure answers this question: out of all the possible ways we can rearrange the observations we got, in what proportion of those arrangements is the sample statistic we care about at least as extreme as the one we got? The answer to that question is the P value.     

Publication bias and merit in ecology

Bias, or any set of factors that influence the general expression of merit, is common in science and is an inevitable by-product of an imperfect but otherwise reasonably objective human pursuit to understand the world we inhabit. In this paper, we explore the conceptual significance of a relatively tractable form of bias, namely publication and dissemination bias. A specific definition is developed, a working model of classification for publication bias is proposed, and an assessment of what we can measure is described. Finally, we offer expectations for ecologists with respect to the significance of bias in the publication process within our discipline. We argue that without explicit consideration of both the qualitative and quantitative aspects of publication bias in ecology, we limit our capacity to fairly assess and best use the science that we as a community produce.     

Multimedia information retrieval and environmental monitoring: Shared perspectives on data fusion

Computer-based remote monitoring of our environment is increasingly based on combining data derived from in-situ-sensors with data derived from remote sources, such as satellite images or CCTV. In such deployments it is necessary to continuously monitor the accuracy of each of the sensor data streams so that we can account for sudden failures of sensors, or errors due to calibration drive or biofouling. In multimedia information retrieval (MMIR), we search through archives of multimedia artefacts like video programs, by implementing several independent retrieval systems or agents, and we combine the outputs of each retrieval agent in order to generate an overall ranking. In this paper we draw parallels between these seemingly very different applications and show how they share several similarities. In the case of environmental monitoring we also need some mechanism by which we can establish the trust and reputation of each contributing sensor, though this is something we do not need in MMIR. In this paper we present an outline of a trust and reputation framework we have developed and deployed for monitoring the performance of sensors in a heterogeneous sensor network.     

Accounting for variability in sample size estimation with applications to nonadherence and estimation of variance and effect size

We consider sample size calculations for testing differences in means between two samples and allowing for different variances in the two groups. Typically, the power functions depend on the sample size and a set of parameters assumed known, and the sample size needed to obtain a prespecified power is calculated. Here, we account for two sources of variability: we allow the sample size in the power function to be a stochastic variable, and we consider estimating the parameters from preliminary data. An example of the first source of variability is nonadherence (noncompliance). We assume that the proportion of subjects who will adhere to their treatment regimen is not known before the study, but that the proportion is a stochastic variable with a known distribution. Under this assumption, we develop simple closed form sample size calculations based on asymptotic normality. The second source of variability is in parameter estimates that are estimated from prior data. For example, we account for variability in estimating the variance of the normal response from existing data which are assumed to have the same variance as the study for which we are calculating the sample size. We show that we can account for the variability of the variance estimate by simply using a slightly larger nominal power in the usual sample size calculation, which we call the calibrated power. We show that the calculation of the calibrated power depends only on the sample size of the existing data, and we give a table of calibrated power by sample size. Further, we consider the calculation of the sample size in the rarer situation where we account for the variability in estimating the standardized effect size from some existing data. This latter situation, as well as several of the previous ones, is motivated by sample size calculations for a Phase II trial of a malaria vaccine candidate.     

The we Gene is a Modifier of the walGene in Mice

Interaction of gene wellhaarig (we) with genes waved alopecia(wal) and hairless (hr) was studied in mice. The mutant gene weis responsible for the development of a specific waved coat in homozygotes. Homozygous mice carrying mutant gene walalso have a wavy coat, though a partial alopecia develops with time in these animals. In homozygotes for thehr gene, hair loss is observed beginning from the age of ten days. A series of crosses we/weand wal/wal yielded animals with we/+wal/wal and we/we wal/wal genotypes. In micewe/+wal/wal carrying gene we at a single dose, alopecia is accelerated significantly as compared to the single-dose homozygotes +/+wal/wal. In we/we wal/wal mice, alopecia starts earlier than in we/+wal/wal mice; by the age of one month, the double homozygotes are almost hairless except for small body areas covered with a sparse coat. In addition, curliness of the first-generation hair in mice we/we wal/wal is much more expressed than in +/+wal/wal and we/we+/+ mice. The obtained evidence suggests that the wegene is a modifier of the wal gene because the former enhances the effects of the walgene, which is confirmed by the earlier onset of alopecia and progression of the latter in mice having the we/+wal/wal genotype and especially in we/we wal/wal animals. The we/we hr/+ mice do not differ in coat from we/we+/+ mice; in both cases, the coat is wavy. The coat of double homozygotes we/we hr/hr, is similar to that of we/we+/+ mice until ten days of age, when the signs of alopecia appear. By the age of 21 days, mice we/we hr/hr have lost their coat completely like mice +/+ hr/hr. Hence, the we gene is a modifier of the walgene though it does not interact with hrgene during the coat formation.     

An assessment of the impacts of molecular oxygen on the evolution of proteomes

Oxygen is not only one of life's essential elements but also a source of protein damage, mutagenesis, and ageing. Many proteome adaptations have been proposed to tackle such stresses and we assessed them using comparative genomics in a phylogenetic context. First, we find that aerobiosis is a trait with important phylogenetic inertia but that oxygen content in proteins is not. Instead, oxygen content is close to the expected values given the nucleotide composition. Accordingly, we find no evidence of oxygen being a scarce resource for protein synthesis even among anaerobes. Second, we searched for counterselection of amino acids more prone to oxidation among aerobes. Only cysteine follows the expected trend, whereas tryptophan follows the inverse one. When analyzing composition in the context of protein structures and residue accessibility, we find that all oxidable residues are avoided at the surface of proteins. Yet, there is no difference between aerobes and anaerobes in this respect, and the effect might be explained by the hydrophobicity of these residues. Third, we revisited the hypothesis that atmospheric enrichment in molecular oxygen led to the development of the communication capabilities of eukaryotes. With a larger data set and adequate controls, we confirm the trend of longer oxygen-rich outer domains in transmembrane proteins of eukaryotes. Yet, we find no significant association between oxygen concentration in the environment and this trait within prokaryotes, suggesting that this difference is clade specific and independent of oxygen availability. We find that genes involved in cellular responses to oxygen are much more frequent among aerobes, and we suggest that they erase most expected differences in terms of proteome composition between organisms facing high and low oxygen concentrations.     

Relaxation of the myocardium of the perfused and ischaemic rabbit heart

The decrease in the rate of relaxation of the myocardium during ischaemic impairment of metabolic processes is accompanied by a decrease in the size of contraction. If we stimulate the ischaemic heart with irregularly distributed pulses we can achieve, by an extrasystolic potentiation mechanism, isolated contractions. If we stimulate the ischaemic heart with irregularly distributed pulses we can achieve, by an extrasystolic potentiation mechanism, isolated contractions of the same size as average contractions in normal perfusion. When comparing the relaxation of such contractions in 15 perfused rabbit hearts, we found a linear correlation between the relaxation rate and the size of the contractions. If we relate to relaxation rate to contraction size, the relaxation rate in early ischaemia (1 min after stopping perfusion) is thus in most cases normal, despite the marked decrease in the size of the contractions. The size of the contractions of the ischaemic mammalian myocardium thus seems to diminish before relaxation (which is likewise energy-dependent) is affected.     

Maximization principles for frequency-dependent selection I: the one-locus two-allele case

In this article we study the one-locus two-allele version of the pairwise-interaction model of frequency-dependent selection in discrete and continuous time. Our main aim is to provide necessary and sufficient conditions for the validity of maximization principles. We provide a systematic approach that covers all possible facets of the dynamical behavior of the model, and we illustrate our results by concrete examples. We show that the mean fitness of the population is nondecreasing if the interaction coefficients are symmetric and positive. Moreover, monotonic convergence to the set of equilibria always occurs, which is not true if we also consider negative interaction coefficients. For asymmetric interaction, we provide necessary conditions when the mean fitness is nondecreasing and sufficient conditions when it is not. Furthermore, in discrete time, we show that limit cycles cannot occur, unless some interaction coefficients are negative.     

Bodies and borders: a new cultural history of medicine

Both medicine and the history of medicine have seen many changes in the last four decades. The way we tell the story of medical developments no longer concentrates on the important doctors and their ideas. The influences of social history in the 1960s and 1970s and cultural history in the 1980s and 1990s have broadened and enriched the interpretations of our medical past. The social historians have helped us to include politics, economics, and the leading ideas of any period we wanted to study; the cultural approach has added ethnography as well as an emphasis on language or discourse.Today there is a new history of medicine, one far more willing to cross disciplinary boundaries to ask questions about how we know what we know and why we do what we do.This article highlights some of the work in the adjoining fields of medical anthropology and of literature and medicine to demonstrate new interests, new questions, and new methods of inquiry. However, although we have cast our nets far more widely in the process of professionalizing the history of medicine, there is a question about whether we have lost the appeal to one of our core constituencies: medical students and physicians. We need to welcome some of the new changes in medical history as in medicine itself; the common goal is to achieve a better understanding of what we have done and what we are doing.     

Seeing and acting at the same time: challenges for brain (and) research

Traditionally, studies of the visual system of nonhuman primates have investigated neurons while the animal fixates a target in a static environment. Clearly, this is not what our everyday life is like; neither the environment nor we are stationary while we act in our world. On the contrary, we constantly move our eyes or limbs. Here we review a number of recent studies describing the brain in a more realistic mode of operation.     

Uncertainties about 'painless' animals

Macer explores whether it is possible to genetically alter animals to reduce or eliminate their capacity to feel pain, whether it would be ethical to do so, and how we would regard animals that do not feel pain. A possible use for such animals would be as subjects for laboratory research. Among the scientific, philosophical, and ethical uncertainties of pain that Macer considers are: can we define pain? how do we measure pain and anxiety? is pain always related to suffering? what is the minimum level of pain that a being must be able to feel before we reach the conclusion that it should not be used by other beings? are we justified in using beings that do not feel pain when we would not be if they did feel pain and suffer from it?     

Letter to my future doctor

Everyone is talking. Physicians, politicians, newspaper columnists, patients, families, authors, talk show hosts, all are debating our right to decide how and when we will die. It is necessary and wise to obtain a medical directive. One question we must ask ourselves as physicians is, Can we do what we ask our patients to do? Here is one physician''s medical directive.     

Mathematical analysis of an age-structured population model with space-limited recruitment

In this paper, we investigate structured population model of marine invertebrate whose life stage is composed of sessile adults and pelagic larvae, such as barnacles contained in a local habitat. First we formulate the basic model as an Cauchy problem on a Banach space to discuss the existence and uniqueness of non-negative solution. Next we define the basic reproduction number R0 to formulate the invasion condition under which the larvae can successfully settle down in the completely vacant habitat. Subsequently we examine existence and stability of steady states. We show that the trivial steady state is globally asymptotically stable if R0 < or = 1, whereas it is unstable if R0 > 1. Furthermore, we show that a positive (non-trivial) steady state uniquely exists if R0 > 1 and it is locally asymptotically stable as far as absolute value of R0 - 1 is small enough.     

Transmission-virulence trade-offs in vector-borne diseases

Though it is commonly supposed that there is a trade-off between virulence and transmission, there is little data and little insight into what it should look like. Here, we consider the specific case of vector-borne parasites (inspired by human malaria) and analyse an embedded model to understand how specific life-cycle aspects may affect this trade-off. First, we find that, for such parasites, the transmission function may have an S-shape. Second, we find that the trade-off obtained for vector-borne parasites is less sensitive to parameter variations than the trade-off obtained for directly transmitted parasites. Third, we find that other parasite traits, such as the conversion from replicative to infective stages, could have important epidemiological implications. Finally, we compare the effect of treatments targeting either the asexual or the sexual parasite life-stage.     

Clustering humans: on biological boundaries

We inquire into the notions of 'boundary' and 'cluster' in the fields of medical genetics, pharmacogenetics, and population genetics. First we show that the two notions are not well discussed in literature. Then we propose a promising explication of them, in which we argue that clustering is always 'property laden', that is, fundamentally dependent on decisions about the properties to be taken into account. In particular we suggest three different kinds of properties (main properties, investigating properties, and catalyzing properties) that have a role in these decisions. That is, we conclude that boundaries and clusters among humans depend on our way of considering nature. Concepts of 'race' and 'ethnic group' are discussed too, since they are the most used clusters among humans.     

Cell cycle-dependent kinetochore localization of condensin complex in Saccharomyces cerevisiae

In budding yeast mitosis is endonuclear and associated with a very limited condensation of the chromosomes. Despite this partial chromosomal condensation, condensin is conserved and essential for the Saccharomyces cerevisiae mitotic cycle. Here, we investigate the localization of condensin during the mitotic cycle. In addition to a constitutive association with rDNA, we have discovered that condensin is localized to the kinetochore in a cell cycle-dependent manner. Shortly after duplication of the spindle pole body, the yeast equivalent of the centrosome, we observed a local enrichment of condensin colocalizing with kinetochore components. This specific association is consistent with mutant phenotypes of chromosome loss and defective sister chromatid separation at anaphase. During a short period of the cell cycle, we observed, at the single cell level, a spatial proximity of condensin and a cohesin rosette, without colocalization. Furthermore, using a genetic screen we demonstrated that condensin localization at kinetochores is specifically impaired in a mutant for ulp2/smt4, an abundant SUMO protease. In conclusion, during chromosome segregation, we established a SUMO-dependent cell cycle-specific condensin concentration colocalizing with kinetochores.     

Novel approaches to map protein interactions

Although we now have the sequence of the human genome at hand, we face the challenge of assigning function to the identified genes. Genes usually ascribe their function through proteins, and the role of proteins is to interact with other molecules. Therefore, if we could map the interactions of proteins we would be able to understand protein function. The challenge of mapping protein interactions is vast and many novel approaches have recently been developed for this task using molecular biology, mass spectrometry and chemiproteomic techniques.