Identifying dynamical modules from genetic regulatory systems: applications to the segment polarity network

BACKGROUND It is widely accepted that genetic regulatory systems are 'modular', in that the whole system is made up of smaller 'subsystems' corresponding to specific biological functions. Most attempts to identify modules in genetic regulatory systems have relied on the topology of the underlying network. However, it is the temporal activity (dynamics) of genes and proteins that corresponds to biological functions, and hence it is dynamics that we focus on here for identifying subsystems. RESULTS Using Boolean network models as an exemplar, we present a new technique to identify subsystems, based on their dynamical properties. The main part of the method depends only on the stable dynamics (attractors) of the system, thus requiring no prior knowledge of the underlying network. However, knowledge of the logical relationships between the network components can be used to describe how each subsystem is regulated. To demonstrate its applicability to genetic regulatory systems, we apply the method to a model of the Drosophila segment polarity network, providing a detailed breakdown of the system. CONCLUSION We have designed a technique for decomposing any set of discrete-state, discrete-time attractors into subsystems. Having a suitable mathematical model also allows us to describe how each subsystem is regulated and how robust each subsystem is against perturbations. However, since the subsystems are found directly from the attractors, a mathematical model or underlying network topology is not necessarily required to identify them, potentially allowing the method to be applied directly to experimental expression data

Interpretation of ambiguous situations: evidence for a dissociation between social and physical threat in Williams syndrome

There is increasing evidence that Williams syndrome (WS) is associated with elevated anxiety that is non-social in nature, including generalised anxiety and fears. To date very little research has examined the cognitive processes associated with this anxiety. In the present research, attentional bias for non-social threatening images in WS was examined using a dot-probe paradigm. Participants were 16 individuals with WS aged between 13 and 34 years and two groups of typically developing controls matched to the WS group on chronological age and attentional control ability respectively. The WS group exhibited a significant attention bias towards threatening images. In contrast, no bias was found for group matched on attentional control and a slight bias away from threat was found in the chronological age matched group. The results are contrasted with recent findings suggesting that individuals with WS do not show an attention bias for threatening faces and discussed in relation to neuroimaging research showing elevated amygdala activation in response to threatening non-social scenes in WS

Calculating the energy spectra of magnetic molecules: application of real- and spin-space symmetries

The determination of the energy spectra of small spin systems as for instance given by magnetic molecules is a demanding numerical problem. In this work we review numerical approaches to diagonalize the Heisenberg Hamiltonian that employ symmetries; in particular we focus on the spin-rotational symmetry SU(2) in combination with point-group symmetries. With these methods one is able to block-diagonalize the Hamiltonian and thus to treat spin systems of unprecedented size. In addition it provides a spectroscopic labeling by irreducible representations that is helpful when interpreting transitions induced by Electron Paramagnetic Resonance (EPR), Nuclear Magnetic Resonance (NMR) or Inelastic Neutron Scattering (INS). It is our aim to provide the reader with detailed knowledge on how to set up such a diagonalization scheme.Comment: 29 pages, many figure

Understanding the impact of antibiotic therapies on the respiratory tract resistome: A novel pooled-template metagenomic sequencing strategy

Determining the effects of antimicrobial therapies on airway microbiology at a population-level is essential. Such analysis allows, for example, surveillance of antibiotic-induced changes in pathogen prevalence, the emergence and spread of antibiotic resistance, and the transmission of multi-resistant organisms. However, current analytical strategies for understanding these processes are limited. Culture- and PCR-based assays for specific microbes require the a priori selection of targets, while antibiotic sensitivity testing typically provides no insight into either the molecular basis of resistance, or the carriage of resistance determinants by the wider commensal microbiota. Shotgun metagenomic sequencing provides an alternative approach that allows the microbial composition of clinical samples to be described in detail, including the prevalence of resistance genes and virulence traits. While highly informative, the application of metagenomics to large patient cohorts can be prohibitively expensive. Using sputum samples from a randomised placebo-controlled trial of erythromycin in adults with bronchiectasis, we describe a novel, cost-effective strategy for screening patient cohorts for changes in resistance gene prevalence. By combining metagenomic screening of pooled DNA extracts with validatory quantitative PCR-based analysis of candidate markers in individual samples, we identify population-level changes in the relative abundance of specific macrolide resistance genes. This approach has the potential to provide an important adjunct to current analytical strategies, particularly within the context of antimicrobial clinical trials

The effect of arm training on thermoregulatory responses and calf volume during upper body exercise

The final publication is available at Springer via https://doi.org/10.1007/s00421-014-2842-9.PURPOSE: The smaller muscle mass of the upper body compared to the lower body may elicit a smaller thermoregulatory stimulus during exercise and thus produce novel training-induced thermoregulatory adaptations. Therefore, the principal aim of the study was to examine the effect of arm training on thermoregulatory responses during submaximal exercise. METHODS: Thirteen healthy male participants (Mean ± SD age 27.8 ± 5.0 years, body mass 74.8 ± 9.5 kg) took part in 8 weeks of arm crank ergometry training. Thermoregulatory and calf blood flow responses were measured during 30 min of arm cranking at 60% peak power (W peak) pre-, and post-training and post-training at the same absolute intensity as pre-training. Core temperature and skin temperatures were measured, along with heat flow at the calf, thigh, upper arm and chest. Calf blood flow using venous occlusion plethysmography was performed pre- and post-exercise and calf volume was determined during exercise. RESULTS: The upper body training reduced aural temperature (0.1 ± 0.3 °C) and heat storage (0.3 ± 0.2 J g(-1)) at a given power output as a result of increased whole body sweating and heat flow. Arm crank training produced a smaller change in calf volume post-training at the same absolute exercise intensity (-1.2 ± 0.8% compared to -2.2 ± 0.9% pre-training; P < 0.05) suggesting reduced leg vasoconstriction. CONCLUSION: Training improved the main markers of aerobic fitness. However, the results of this study suggest arm crank training additionally elicits physiological responses specific to the lower body which may aid thermoregulation.Peer reviewedFinal Accepted Versio

A Functional Role for Modality-Specific Perceptual Systems in Conceptual Representations

Theories of embodied cognition suggest that conceptual processing relies on the same neural resources that are utilized for perception and action. Evidence for these perceptual simulations comes from neuroimaging and behavioural research, such as demonstrations of somatotopic motor cortex activations following the presentation of action-related words, or facilitation of grasp responses following presentation of object names. However, the interpretation of such effects has been called into question by suggestions that neural activation in modality-specific sensorimotor regions may be epiphenomenal, and merely the result of spreading activations from “disembodied”, abstracted, symbolic representations. Here, we present two studies that focus on the perceptual modalities of touch and proprioception. We show that in a timed object-comparison task, concurrent tactile or proprioceptive stimulation to the hands facilitates conceptual processing relative to control stimulation. This facilitation occurs only for small, manipulable objects, where tactile and proprioceptive information form part of the multimodal perceptual experience of interacting with such objects, but facilitation is not observed for large, nonmanipulable objects where such perceptual information is uninformative. Importantly, these facilitation effects are independent of motor and action planning, and indicate that modality-specific perceptual information plays a functionally constitutive role in our mental representations of objects, which supports embodied assumptions that concepts are grounded in the same neural systems that govern perception and action

Does the Reading of Different Orthographies Produce Distinct Brain Activity Patterns? An ERP Study

Orthographies vary in the degree of transparency of spelling-sound correspondence. These range from shallow orthographies with transparent grapheme-phoneme relations, to deep orthographies, in which these relations are opaque. Only a few studies have examined whether orthographic depth is reflected in brain activity. In these studies a between-language design was applied, making it difficult to isolate the aspect of orthographic depth. In the present work this question was examined using a within-subject-and-language investigation. The participants were speakers of Hebrew, as they are skilled in reading two forms of script transcribing the same oral language. One form is the shallow pointed script (with diacritics), and the other is the deep unpointed script (without diacritics). Event-related potentials (ERPs) were recorded while skilled readers carried out a lexical decision task in the two forms of script. A visual non-orthographic task controlled for the visual difference between the scripts (resulting from the addition of diacritics to the pointed script only). At an early visual-perceptual stage of processing (∼165 ms after target onset), the pointed script evoked larger amplitudes with longer latencies than the unpointed script at occipital-temporal sites. However, these effects were not restricted to orthographic processing, and may therefore have reflected, at least in part, the visual load imposed by the diacritics. Nevertheless, the results implied that distinct orthographic processing may have also contributed to these effects. At later stages (∼340 ms after target onset) the unpointed script elicited larger amplitudes than the pointed one with earlier latencies. As this latency has been linked to orthographic-linguistic processing and to the classification of stimuli, it is suggested that these differences are associated with distinct lexical processing of a shallow and a deep orthography