A `bright zone' in male hoverfly (Eristalis tenax) eyes and associated faster motion detection and increased contrast sensitivity

Eyes of the hoverfly Eristalis tenax are sexually dimorphic such that males have a fronto-dorsal region of large facets. In contrast to other large flies in which large facets are associated with a decreased interommatidial angle to form a dorsal `acute zone' of increased spatial resolution, we show that a dorsal region of large facets in males appears to form a `bright zone' of increased light capture without substantially increased spatial resolution. Theoretically, more light allows for increased performance in tasks such as motion detection. To determine the effect of the bright zone on motion detection, local properties of wide field motion detecting neurons were investigated using localized sinusoidal gratings. The pattern of local preferred directions of one class of these cells, the HS cells, in Eristalis is similar to that reported for the blowfly Calliphora. The bright zone seems to contribute to local contrast sensitivity; high contrast sensitivity exists in portions of the receptive field served by large diameter facet lenses of males and is not observed in females. Finally, temporal frequency tuning is also significantly faster in this frontal portion of the world, particularly in males, where it overcompensates for the higher spatial-frequency tuning and shifts the predicted local velocity optimum to higher speeds. These results indicate that increased retinal illuminance due to the bright zone of males is used to enhance contrast sensitivity and speed motion detector responses. Additionally, local neural properties vary across the visual world in a way not expected if HS cells serve purely as matched filters to measure yaw-induced visual motion

Synergy and redundancy in the Granger causal analysis of dynamical networks

We analyze by means of Granger causality the effect of synergy and redundancy in the inference (from time series data) of the information flow between subsystems of a complex network. Whilst we show that fully conditioned Granger causality is not affected by synergy, the pairwise analysis fails to put in evidence synergetic effects. In cases when the number of samples is low, thus making the fully conditioned approach unfeasible, we show that partially conditioned Granger causality is an effective approach if the set of conditioning variables is properly chosen. We consider here two different strategies (based either on informational content for the candidate driver or on selecting the variables with highest pairwise influences) for partially conditioned Granger causality and show that depending on the data structure either one or the other might be valid. On the other hand, we observe that fully conditioned approaches do not work well in presence of redundancy, thus suggesting the strategy of separating the pairwise links in two subsets: those corresponding to indirect connections of the fully conditioned Granger causality (which should thus be excluded) and links that can be ascribed to redundancy effects and, together with the results from the fully connected approach, provide a better description of the causality pattern in presence of redundancy. We finally apply these methods to two different real datasets. First, analyzing electrophysiological data from an epileptic brain, we show that synergetic effects are dominant just before seizure occurrences. Second, our analysis applied to gene expression time series from HeLa culture shows that the underlying regulatory networks are characterized by both redundancy and synergy

In Vivo Fluorescence Imaging of E-Selectin: Quantitative Detection of Endothelial Activation in Arthritis

Rheumatoid arthritis (RA) is a chronic progressive systemic inflammatory disease, characterized by synovial inflammation and localized destruction of cartilage and bone. Heterogeneity in the clinical presentation of RA and uncertainty about which patients will respond to treatment makes diagnosis and management challenging. Fluorescent imaging in the near infrared (NIR) spectrum significantly decreases tissue autofluorescence offering unique potential to detect specific molecular targets in vivo. E-selectin or endothelial adhesion molecule-1 (ELAM-1), a 115kDa glycoprotein induced on endothelial cells in response to pro-inflammatory cytokines involved in RA, such as interleukin (IL)-1 beta and tumour necrosis factor alpha (TNF alpha). E-selectin has been well validated as a potential biomarker of disease activity. My study aimed to investigate whether E-selectin targeted optical imaging in vivo could be developed as a sensitive, specific and quantifiable preclinical molecular imaging technique, and also whether this approach could be used to delineate the molecular effects of novel therapies. I utilised anti-E-selectin antibody labelled with NIR fluorophore in a mouse model of paw swelling induced by intra-plantar injection of TNF alpha, and in acute collagen-induced arthritis (CIA) in DBA/1 mice, a widely used model of RA. E-selectin generated signal, localised to points of maximal clinical inflammation in the inflamed mouse paw in both models with significant differences to control antibody. Binding of anti-E-selectin antibody was also demonstrated by immunohistochemistry in both models. The ability of E-selectin targeted imaging to detect sub-clinical endothelial activation was also investigated, demonstrating that E-selectin may be an excellent way of determining subclinical vascular activation in CIA. Finally the effect of novel targeted therapy – RB200 which blocks epidermal growth factor (EGF) signalling was investigated. This demonstrated that E-selectin targeted signal could be absolutely abrogated to a level seen in unimmunised healthy control animals, following combination treatment with RB200 and the TNF alpha inhibitor etanercept. E-selectin targeted optical imaging is a viable in vivo imaging technique that can also be applied to quantify disease and investigate the effects of novel molecular therapies. It holds significant promise as a molecular imaging technique for future translation into the clinic for patients with rheumatoid arthritis and other inflammatory diseases

Episignature analysis of moderate effects and mosaics

DNA methylation classifiers (episignatures) help to determine the pathogenicity of variants of uncertain significance (VUS). However, their sensitivity is limited due to their training on unambiguous cases with strong-effect variants so that the classification of variants with reduced effect size or in mosaic state may fail. Moreover, episignature evaluation of mosaics as a function of their degree of mosaicism has not been developed so far. We improved episignatures with respect to three categories. Applying (i) minimum-redundancy-maximum-relevance feature selection we reduced their length by up to one order of magnitude without loss of accuracy. Performing (ii) repeated re-training of a support vector machine classifier by step-wise inclusion of cases in the training set that reached probability scores larger than 0.5, we increased the sensitivity of the episignature-classifiers by 30%. In the newly diagnosed patients we confirmed the association between DNA methylation aberration and age at onset of KMT2B-deficient dystonia. Moreover, we found evidence for allelic series, including KMT2B-variants with moderate effects and comparatively mild phenotypes such as late-onset focal dystonia. Retrained classifiers also can detect mosaics that previously remained below the 0.5-threshold, as we showed for KMT2D-associated Kabuki syndrome. Conversely, episignature-classifiers are able to revoke erroneous exome calls of mosaicism, as we demonstrated by (iii) comparing presumed mosaic cases with a distribution of artificial in silico-mosaics that represented all the possible variation in degree of mosaicism, variant read sampling and methylation analysis

Properties and Detection of Spin Nematic Order in Strongly Correlated Electron Systems

A spin nematic is a state which breaks spin SU(2) symmetry while preserving translational and time reversal symmetries. Spin nematic order can arise naturally from charge fluctuations of a spin stripe state. Focusing on the possible existence of such a state in strongly correlated electron systems, we build a nematic wave function starting from a t-J type model. The nematic is a spin-two operator, and therefore does not couple directly to neutrons. However, we show that neutron scattering and Knight shift experiments can detect the spin anisotropy of electrons moving in a nematic background. We find the mean field phase diagram for the nematic taking into account spin-orbit effects.Comment: 13 pages, 11 figures. (v2) References adde

Spike detection using the continuous wavelet transform

This paper combines wavelet transforms with basic detection theory to develop a new unsupervised method for robustly detecting and localizing spikes in noisy neural recordings. The method does not require the construction of templates, or the supervised setting of thresholds. We present extensive Monte Carlo simulations, based on actual extracellular recordings, to show that this technique surpasses other commonly used methods in a wide variety of recording conditions. We further demonstrate that falsely detected spikes corresponding to our method resemble actual spikes more than the false positives of other techniques such as amplitude thresholding. Moreover, the simplicity of the method allows for nearly real-time execution

The information transmitted by spike patterns in single neurons

Spike patterns have been reported to encode sensory information in several brain areas. Here we assess the role of specific patterns in the neural code, by comparing the amount of information transmitted with different choices of the readout neural alphabet. This allows us to rank several alternative alphabets depending on the amount of information that can be extracted from them. One can thereby identify the specific patterns that constitute the most prominent ingredients of the code. We finally discuss the interplay of categorical and temporal information in the amount of synergy or redundancy in the neural code.Comment: To be published in Journal of Physiology Paris 200