A habituation account of change detection in same/different judgments

We investigated the basis of change detection in a short-term priming task. In two experiments, participants were asked to indicate whether or not a target word was the same as a previously presented cue. Data from an experiment measuring magnetoencephalography failed to find different patterns for “same” and “different” responses, consistent with the claim that both arise from a common neural source, with response magnitude defining the difference between immediate novelty versus familiarity. In a behavioral experiment, we tested and confirmed the predictions of a habituation account of these judgments by comparing conditions in which the target, the cue, or neither was primed by its presentation in the previous trial. As predicted, cue-primed trials had faster response times, and target-primed trials had slower response times relative to the neither-primed baseline. These results were obtained irrespective of response repetition and stimulus–response contingencies. The behavioral and brain activity data support the view that detection of change drives performance in these tasks and that the underlying mechanism is neuronal habituation

Delineation of Stage Specific Expression of Plasmodium falciparum EBA-175 by Biologically Functional Region II Monoclonal Antibodies

EBA-175 binds its receptor sialic acids on glycophorin A when invading erythrocytes. The receptor-binding region (RII) contains two cysteine-rich domains with similar cysteine motifs (F1 and F2). Functional relationships between F1 and F2 domains and characterization of EBA-175 were studied using specific monoclonal antibodies (mAbs) against these domains..The role of the F1 and F2 domains in erythrocyte invasion and binding was elucidated with mAbs. These mAbs interfere with native EBA-175 binding to erythrocyte in a synergistic fashion. The stage specific expression of EBA-175 showed that the primary focus of activity was the merozoite stage. A recombinant RII protein vaccine consisting of both F1 and F2 domains that could induce synergistic activity should be optimal for induction of antibody responses that interfere with merozoite invasion of erythrocytes

Looking to the future of zebrafish as a model to understand the genetic basis of eye disease

In this brief commentary, we provide some of our thoughts and opinions on the current and future use of zebrafish to model human eye disease, dissect pathological progression and advance in our understanding of the genetic bases of microphthalmia, andophthalmia and coloboma (MAC) in humans. We provide some background on eye formation in fish and conservation and divergence across vertebrates in this process, discuss different approaches for manipulating gene function and speculate on future research areas where we think research using fish may prove to be particularly effective

Applying unmixing to gene expression data for tumor phylogeny inference

<p>Abstract</p> <p>Background</p> <p>While in principle a seemingly infinite variety of combinations of mutations could result in tumor development, in practice it appears that most human cancers fall into a relatively small number of "sub-types," each characterized a roughly equivalent sequence of mutations by which it progresses in different patients. There is currently great interest in identifying the common sub-types and applying them to the development of diagnostics or therapeutics. Phylogenetic methods have shown great promise for inferring common patterns of tumor progression, but suffer from limits of the technologies available for assaying differences between and within tumors. One approach to tumor phylogenetics uses differences between single cells within tumors, gaining valuable information about intra-tumor heterogeneity but allowing only a few markers per cell. An alternative approach uses tissue-wide measures of whole tumors to provide a detailed picture of averaged tumor state but at the cost of losing information about intra-tumor heterogeneity.</p> <p>Results</p> <p>The present work applies "unmixing" methods, which separate complex data sets into combinations of simpler components, to attempt to gain advantages of both tissue-wide and single-cell approaches to cancer phylogenetics. We develop an unmixing method to infer recurring cell states from microarray measurements of tumor populations and use the inferred mixtures of states in individual tumors to identify possible evolutionary relationships among tumor cells. Validation on simulated data shows the method can accurately separate small numbers of cell states and infer phylogenetic relationships among them. Application to a lung cancer dataset shows that the method can identify cell states corresponding to common lung tumor types and suggest possible evolutionary relationships among them that show good correspondence with our current understanding of lung tumor development.</p> <p>Conclusions</p> <p>Unmixing methods provide a way to make use of both intra-tumor heterogeneity and large probe sets for tumor phylogeny inference, establishing a new avenue towards the construction of detailed, accurate portraits of common tumor sub-types and the mechanisms by which they develop. These reconstructions are likely to have future value in discovering and diagnosing novel cancer sub-types and in identifying targets for therapeutic development.</p

Short Term Synaptic Depression Imposes a Frequency Dependent Filter on Synaptic Information Transfer

Depletion of synaptic neurotransmitter vesicles induces a form of short term depression in synapses throughout the nervous system. This plasticity affects how synapses filter presynaptic spike trains. The filtering properties of short term depression are often studied using a deterministic synapse model that predicts the mean synaptic response to a presynaptic spike train, but ignores variability introduced by the probabilistic nature of vesicle release and stochasticity in synaptic recovery time. We show that this additional variability has important consequences for the synaptic filtering of presynaptic information. In particular, a synapse model with stochastic vesicle dynamics suppresses information encoded at lower frequencies more than information encoded at higher frequencies, while a model that ignores this stochasticity transfers information encoded at any frequency equally well. This distinction between the two models persists even when large numbers of synaptic contacts are considered. Our study provides strong evidence that the stochastic nature neurotransmitter vesicle dynamics must be considered when analyzing the information flow across a synapse

Sex-specific reproductive behaviours and paternity in free-ranging Barbary macaques (Macaca sylvanus)

In a wide variety of species, male reproductive success is determined by contest for access to females. Among multi-male primate groups, however, factors in addition to male competitive ability may also influence paternity outcome, although their exact nature and force is still largely unclear. Here, we have investigated in a group of free-ranging Barbary macaques whether paternity is determined on the pre- or postcopulatory level and how male competitive ability and female direct mate choice during the female fertile phase are related to male reproductive success. Behavioural observations were combined with faecal hormone analysis for timing of the fertile phase (13 cycles, 8 females) and genetic paternity analysis (n = 12). During the fertile phase, complete monopolisation of females did not occur. Females were consorted for only 49% of observation time, and all females had ejaculatory copulations with several males. Thus, in all cases, paternity was determined on the postcopulatory level. More than 80% of infants were sired by high-ranking males, and this reproductive skew was related to both, male competitive ability and female direct mate choice as high-ranking males spent more time in consort with females than low-ranking males, and females solicited copulations mainly from dominant males. As most ejaculatory copulations were female-initiated, female direct mate choice appeared to have the highest impact on male reproductive success. However, female preference was not directly translated into paternity, as fathers were not preferred over non-fathers in terms of solicitation, consortship and mating behaviour. Collectively, our data show that in the Barbary macaque, both sexes significantly influence male mating success, but that sperm of several males generally compete within the female reproductive tract and that therefore paternity is determined by mechanisms operating at the postcopulatory level