BTW: a web server for Boltzmann time warping of gene expression time series

Dynamic time warping (DTW) is a well-known quadratic time algorithm to determine the smallest distance and optimal alignment between two numerical sequences, possibly of different length. Originally developed for speech recognition, this method has been used in data mining, medicine and bioinformatics. For gene expression time series data, time warping distance is arguably a more flexible tool to determine genes having similar temporal expression, hence possibly related biological function, than either Euclidean distance or correlation coefficient—especially since time warping accommodates sequences of different length. The BTW web server allows a user to upload two tab-separated text files A,B of gene expression data, each possibly having a different number of time intervals of different durations. BTW then computes time warping distance between each gene of A with each gene of B, using a recently developed symmetric algorithm which additionally computes the Boltzmann partition function and outputs Boltzmann pair probabilities. The Boltzmann pair probabilities, not available with any other existent software, suggest possible biological significance of certain positions in an optimal time warping alignment. Availability:

DiANNA: a web server for disulfide connectivity prediction

Correctly predicting the disulfide bond topology in a protein is of crucial importance for the understanding of protein function and can be of great help for tertiary prediction methods. The web server outputs the disulfide connectivity prediction given input of a protein sequence. The following procedure is performed. First, PSIPRED is run to predict the protein's secondary structure, then PSIBLAST is run against the non-redundant SwissProt to obtain a multiple alignment of the input sequence. The predicted secondary structure and the profile arising from this alignment are used in the training phase of our neural network. Next, cysteine oxidation state is predicted, then each pair of cysteines in the protein sequence is assigned a likelihood of forming a disulfide bond—this is performed by means of a novel architecture (diresidue neural network). Finally, Rothberg's implementation of Gabow's maximum weighted matching algorithm is applied to diresidue neural network scores in order to produce the final connectivity prediction. Our novel neural network-based approach achieves results that are comparable and in some cases better than the current state-of-the-art methods

DiANNA 1.1: an extension of the DiANNA web server for ternary cysteine classification

DiANNA is a recent state-of-the-art artificial neural network and web server, which determines the cysteine oxidation state and disulfide connectivity of a protein, given only its amino acid sequence. Version 1.0 of DiANNA uses a feed-forward neural network to determine which cysteines are involved in a disulfide bond, and employs a novel architecture neural network to predict which half-cystines are covalently bound to which other half-cystines. In version 1.1 of DiANNA, described here, we extend functionality by applying a support vector machine with spectrum kernel for the cysteine classification problem—to determine whether a cysteine is reduced (free in sulfhydryl state), half-cystine (involved in a disulfide bond) or bound to a metallic ligand. In the latter case, DiANNA predicts the ligand among iron, zinc, cadmium and carbon. Available at:

Vestibular cognition: state-of-the-art and future directions

Vestibular information has been traditionally considered as a specialized input for basic orienting behaviours, such as oculo-motor adjustments, postural control and gaze orientation. However, in the past two decades a widespread vestibular network in the human brain has been identified, that goes far beyond the low-level reflex circuits emphasized by earlier work. Because this vestibular cortical network is so widely distributed, it could, in principle, impact multiple neurocognitive functions in health and disease. This paper focuses on the relations between vestibular input, vestibular networks, and vestibular interventions by providing the authors’ personal viewpoint on the state-of-the-art of vestibular cognitive neuropsychology, and its potential relevance for neurorehabilitation

Vestibular–somatosensory interactions: a mechanism in search of a function?

No unimodal vestibular cortex has been identified in the human brain. Rather, vestibular inputs are strongly integrated with signals from other sensory modalities, such as vision, touch and proprioception. This convergence could reflect an important mechanism for maintaining a perception of the body, including individual body parts, relative to the rest of the environment. Neuroimaging, electrophysiological and psychophysical studies showed evidence for multisensory interactions between vestibular and somatosensory signals. However, no convincing overall theoretical framework has been proposed for vestibular–somatosensory interactions, and it remains unclear whether such percepts are by-products of neural convergence, or a functional multimodal integration. Here we review the current literature on vestibular–multisensory interactions in order to develop a framework for understanding the functions of such multimodal interaction. We propose that the target of vestibular–somatosensory interactions is a form of self-representation

The vestibular body: vestibular contributions to bodily representations

Vestibular signals are integrated with signals from other sensory modalities. This convergence could reflect an important mechanism for maintaining the perception of the body. Here we review the current literature in order to develop a framework for understanding how the vestibular system contributes to body representation. According to recent models, we distinguish between three processes for body representation, and we look at whether vestibular signals might influence each process. These are (i) somatosensation, the primary sensory processing of somatic stimuli, (ii) somatoperception, the processes of constructing percepts and experiences of somatic objects and events and (iii) somatorepresentation, the knowledge about the body as a physical object in the world. Vestibular signals appear to contribute to all three levels in this model of body processing. Thus, the traditional view of the vestibular system as a low-level, dedicated orienting module tends to underestimate the pervasive role of vestibular input in bodily self-awareness

Transforming the Thermal Grill Effect by crossing the fingers

The relation between pain perception and spatial representation of the body is poorly understood. In the thermal grill illusion (TGI), alternating non-noxious warm and cold temperatures cause a paradoxical, sometimes painful, sensation of burning heat [1]. We combined thermal grill stimulation with crossing the fingers to investigate whether nociceptively mediated sensation depends on the somatotopic or spatiotopic configuration of thermal inputs. We stimulated the index, middle, and ring fingers when the middle finger either was or was not crossed over the index to generate “warm-cold-warm” patterns in either somatotopic or spatiotopic coordinates. Participants adjusted a temperature delivered to the other hand until it matched their perception of the cold target finger (index or middle). We found significant temperature overestimation when the target was central within the spatial configuration (warm-cold-warm) compared to when it was peripheral (cold-warm-warm). Crucially, this effect depended on the spatiotopic configuration of thermal inputs, but it was independent of the finger posture and present for both index and middle target fingers—the thermal grill effect for the middle finger was abolished when it was crossed over the index to adopt a spatiotopically peripheral position, while the same effect was newly generated for the index finger by the same postural change. Our results suggest that the locations of multiple stimuli are remapped into external space as a group; nociceptively mediated sensations depended not on the body posture, but rather on the external spatial configuration formed by the pattern of thermal stimuli in each posture

Multisensory interactions between vestibular, visual and somatosensory signals

Vestibular inputs are constantly processed and integrated with signals from other sensory modalities, such as vision and touch. The multiply-connected nature of vestibular cortical anatomy led us to investigate whether vestibular signals could participate in a multi-way interaction with visual and somatosensory perception. We used signal detection methods to identify whether vestibular stimulation might interact with both visual and somatosensory events in a detection task. Participants were instructed to detect near-threshold somatosensory stimuli that were delivered to the left index finger in one half of experimental trials. A visual signal occurred close to the finger in half of the trials, independent of somatosensory stimuli. A novel Near infrared caloric vestibular stimulus (NirCVS) was used to artificially activate the vestibular organs. Sham stimulations were used to control for non-specific effects of NirCVS. We found that both visual and vestibular events increased somatosensory sensitivity. Critically, we found no evidence for supra-additive multisensory enhancement when both visual and vestibular signals were administered together: in fact, we found a trend towards sub-additive interaction. The results are compatible with a vestibular role in somatosensory gain regulation

Galvanic vestibular stimulation increases novelty in free selection of manual actions

Making optimal choices in changing environments implies the ability to balance routine, exploitative patterns of behavior with novel, exploratory ones. We investigated whether galvanic vestibular stimulation (GVS) interferes with the balance between exploratory and exploitative behaviors in a free action selection task. Brief right-anodal and left-cathodal GVS or left-anodal and right-cathodal GVS were delivered at random to activate sensorimotor circuits in the left and right hemisphere, respectively. A sham stimulation condition was included. Participants endogenously generated sequences of possible actions, by freely choosing successive movements of the index or middle finger of the left or right hand. Left-anodal and right-cathodal GVS, which preferentially activates the vestibular projections in the right cerebral hemisphere, increased the novelty in action sequences, as measured by the number of runs in the sequences. In contrast, right-anodal and left-cathodal GVS decreased the number of runs. There was no evidence of GVS-induced spatial bias in action choices. Our results confirm previous reports showing a polarity-dependent effect of GVS on the balance between novel and routine responses, and thus between exploratory and exploitative behaviors

Thermonociceptive interaction: interchannel pain modulation occurs before intrachannel convergence of warmth

Nonnoxious warmth reduces both perceived pain intensity and the amplitude of EEG markers of pain. However, the spatial properties of thermonociceptive interaction, and the level of sensory processing at which it occurs, remain unclear. We investigated whether interchannel warmth-pain interactions occur before or after intrachannel spatial summation of warmth. Warm stimuli were applied to the fingers of the right hand. Their number and location were manipulated in different conditions. A concomitant noxious test pulse was delivered to the middle finger using a CO2 laser. We replicated the classical suppressive effect of warmth on both perceived pain intensity and EEG markers. Importantly, inhibition of pain was not affected by the location and the number of thermal stimuli, even though they increased the perceived intensity of warmth. Our results therefore suggest that the inhibitory effect of warmth on pain is not somatotopically organized. The results also rule out the possibility that warmth affects nociceptive processing after intrachannel warmth summation