Why Neurons Are Not the Right Level of Abstraction for Implementing Cognition

International audienceThe cortex accounts for 70% of the brain volume. The human cortex is made of micro-columns, arrangements of 110 cortical neurons (Mountcastle), grouped in by the thousand in so-called macro-colums (or columns) which belong to the same functional unit as exemplified by Nobel laureates Hubel and Wiesel with the orientation columns of the primary visual cortex. The cortical column activity does not exhibit the limitations of single neurons: activation can be sustained for very long periods (sec.) instead of been transient and subject to fatigue. Therefore, the cortical column has been proposed as the building block of cognition by several researchers, but to not effect – since explanations about how the cognition works at the column level were missing. Thanks to the Theory of neuronal Cognition, it is no more the case. The cortex functionality is cut into small areas: the cortical maps. Today, about 80 cortical maps are known in the primary and secondary cortex [1]. These maps form a hierarchical organization. A cortical map is a functional structure encompassing several thousands of cortical columns. The function of such maps (also known as Kohonen maps) is to build topographic (i.e., organized and localized) representations of the input stimulii (events). This organization is such that similar inputs activate either the same cortical column or neighboring columns. Also, the more frequent the stimulus, the greater the number of cortical columns involved. Each map acts as a novelty detector and a filter. Events are reported as patterns of activations on various maps, each map specialized in a specific " dimension ". Spatial and temporal coordinates of events are linked to activations within the hippo-campus and define de facto the episodic memory. Learning is achieved at neuronal level using the famous Hebb's law: " Neurons active in the same time frame window reinforce their connections ". This rule does not respect " causality ". This, plus the fact that there is at least as much feedback connections as there are feed-forward ones, explain why a high level cortical activation generates a low level cortical pattern of activations – the same one that would trigger this high level activity. Therefore, our opinion is that the true building block of the cognition is a set of feed-forward and feedback connections between at least two maps, each map a novelty detector

TFM-Explorer: mining cis-regulatory regions in genomes

DNA-binding transcription factors (TFs) play a central role in transcription regulation, and computational approaches that help in elucidating complex mechanisms governing this basic biological process are of great use. In this perspective, we present the TFM-Explorer web server that is a toolbox to identify putative TF binding sites within a set of upstream regulatory sequences of genes sharing some regulatory mechanisms. TFM-Explorer finds local regions showing overrepresentation of binding sites. Accepted organisms are human, mouse, rat, chicken and drosophila. The server employs a number of features to help users to analyze their data: visualization of selected binding sites on genomic sequences, and selection of cis-regulatory modules. TFM-Explorer is available at http://bioinfo.lifl.fr/TFM

A Biologically Plausible SOM Representation of the Orthographic Form of 50,000 French Words

International audienceRecently, an important aspect of human visual word recognition has been characterized. The letter position is encoded in our brain using an explicit representation of order based on letter pairs: the open-bigram coding [15]. We hypothesize that spelling has evolved in order to minimize reading errors. Therefore, word recognition using bigrams — instead of letters — should be more efficient. First, we study the influence of the size of the neighborhood, which defines the number of bigrams per word, on the performance of the matching between bigrams and word. Our tests are conducted against one of the best recognition solutions used today by the industry, which matches letters to words. Secondly, we build a cortical map representation of the words in the bigram space — which implies numerous experiments in order to achieve a satisfactory projection. Third, we develop an ultra-fast version of the self-organizing map in order to achieve learning in minutes instead of months

Extensive variation in synonymous substitution rates in mitochondrial genes of seed plants

<p>Abstract</p> <p>Background</p> <p>It has long been known that rates of synonymous substitutions are unusually low in mitochondrial genes of flowering and other land plants. Although two dramatic exceptions to this pattern have recently been reported, it is unclear how often major increases in substitution rates occur during plant mitochondrial evolution and what the overall magnitude of substitution rate variation is across plants.</p> <p>Results</p> <p>A broad survey was undertaken to evaluate synonymous substitution rates in mitochondrial genes of angiosperms and gymnosperms. Although most taxa conform to the generality that plant mitochondrial sequences evolve slowly, additional cases of highly accelerated rates were found. We explore in detail one of these new cases, within the genus <it>Silene</it>. A roughly 100-fold increase in synonymous substitution rate is estimated to have taken place within the last 5 million years and involves only one of ten species of <it>Silene </it>sampled in this study. Examples of unusually slow sequence evolution were also identified. Comparison of the fastest and slowest lineages shows that synonymous substitution rates vary by four orders of magnitude across seed plants. In other words, some plant mitochondrial lineages accumulate more synonymous change in 10,000 years than do others in 100 million years. Several perplexing cases of gene-to-gene variation in sequence divergence within a plant were uncovered. Some of these probably reflect interesting biological phenomena, such as horizontal gene transfer, mitochondrial-to-nucleus transfer, and intragenomic variation in mitochondrial substitution rates, whereas others are likely the result of various kinds of errors.</p> <p>Conclusion</p> <p>The extremes of synonymous substitution rates measured here constitute by far the largest known range of rate variation for any group of organisms. These results highlight the utility of examining absolute substitution rates in a phylogenetic context rather than by traditional pairwise methods. Why substitution rates are generally so low in plant mitochondrial genomes yet occasionally increase dramatically remains mysterious.</p

ART2 et apprentissage de séquences de mots : l'ordre compte

ISBN : 978-2-9532965-0-1Un réseau Adaptive Resonance Theory a été utilisé pour simuler l'apprentissage des formes orthographiques des mots vus par les enfants. Il a été démontré qu'une modélisation par carte auto-organisatrice permet de rendre compte des performances de l'enfant si on conserve les probabilités d'apparition des mots de la base d'apprentissage. Nous montrons dans cet article avec ART2, que l'ordre d'apparition des mots joue aussi un rôle significatif dans la discrimination des mots plus ou moins orthographiquement voisins. Il en découle une hypothése de construction de corpus favorable é l'apprentissage de la lecture de ce type de mots

Impact of a comprehensive prevention programme aimed at reducing incivility and verbal violence against healthcare workers in a French ophthalmic emergency department: an interrupted time-series study.

Primary prevention, comprising patient-oriented and environmental interventions, is considered to be one of the best ways to reduce violence in the emergency department (ED). We assessed the impact of a comprehensive prevention programme aimed at preventing incivility and verbal violence against healthcare professionals working in the ophthalmology ED (OED) of a university hospital. The programme was designed to address long waiting times and lack of information. It combined a computerised triage algorithm linked to a waiting room patient call system, signage to assist patients to navigate in the OED, educational messages broadcast in the waiting room, presence of a mediator and video surveillance. All patients admitted to the OED and those accompanying them. Single-centre prospective interrupted time-series study conducted over 18 months. Violent acts self-reported by healthcare workers committed by patients or those accompanying them against healthcare workers. Waiting time and length of stay. There were a total of 22 107 admissions, including 272 (1.4%) with at least one act of violence reported by the healthcare workers. Almost all acts of violence were incivility or verbal harassment. The rate of violence significantly decreased from the pre-intervention to the intervention period (24.8, 95% CI 20.0 to 29.5, to 9.5, 95% CI 8.0 to 10.9, acts per 1000 admissions, p&lt;0.001). An immediate 53% decrease in the violence rate (incidence rate ratio=0.47, 95% CI 0.27 to 0.82, p=0.0121) was observed in the first month of the intervention period, after implementation of the triage algorithm. A comprehensive prevention programme targeting patients and environment can reduce self-reported incivility and verbal violence against healthcare workers in an OED. NCT02015884

Multifaceted intervention to decrease the rate of severe postpartum haemorrhage: the PITHAGORE6 cluster-randomised controlled trial.: Intervention to decrease severe postpartum haemorrhage

International audienceOBJECTIVE: Decreasing the prevalence of severe postpartum haemorrhages (PPH) is a major obstetrical challenge. These are often considered to be associated with substandard initial care. Strategies to increase the appropriateness of early management of PPH must be assessed. We tested the hypothesis that a multifaceted intervention aimed at increasing the translation into practice of a protocol for early management of PPH, would reduce the incidence of severe PPH. DESIGN: Cluster-randomised trial. POPULATION: 106 maternity units in six French regions. METHODS: Maternity units were randomly assigned to receive the intervention, or to have the protocol passively disseminated. The intervention combined outreach visits to discuss the protocol in each local context, reminders, and peer reviews of severe incidents, and was implemented in each maternity hospital by a team pairing an obstetrician and a midwife. MAIN OUTCOME MEASURES: The primary outcome was the incidence of severe PPH, defined as a composite of one or more of: transfusion, embolisation, surgical procedure, transfer to intensive care, peripartum haemoglobin decrease of 4 g/dl or more, death. The main secondary outcomes were PPH management practices. RESULTS: The mean rate of severe PPH was 1.64% (SD 0.80) in the intervention units and 1.65% (SD 0.96) in control units; difference not significant. Some elements of PPH management were applied more frequently in intervention units-help from senior staff (P = 0.005), or tended to - second-line pharmacological treatment (P = 0.06), timely blood test (P = 0.09). CONCLUSION: This educational intervention did not affect the rate of severe PPH as compared with control units, although it improved some practices

Efficient and accurate P-value computation for Position Weight Matrices

<p>Abstract</p> <p>Background</p> <p>Position Weight Matrices (PWMs) are probabilistic representations of signals in sequences. They are widely used to model approximate patterns in DNA or in protein sequences. The usage of PWMs needs as a prerequisite to knowing the statistical significance of a word according to its score. This is done by defining the P-value of a score, which is the probability that the background model can achieve a score larger than or equal to the observed value. This gives rise to the following problem: Given a P-value, find the corresponding score threshold. Existing methods rely on dynamic programming or probability generating functions. For many examples of PWMs, they fail to give accurate results in a reasonable amount of time.</p> <p>Results</p> <p>The contribution of this paper is two fold. First, we study the theoretical complexity of the problem, and we prove that it is NP-hard. Then, we describe a novel algorithm that solves the P-value problem efficiently. The main idea is to use a series of discretized score distributions that improves the final result step by step until some convergence criterion is met. Moreover, the algorithm is capable of calculating the exact P-value without any error, even for matrices with non-integer coefficient values. The same approach is also used to devise an accurate algorithm for the reverse problem: finding the P-value for a given score. Both methods are implemented in a software called TFM-PVALUE, that is freely available.</p> <p>Conclusion</p> <p>We have tested TFM-PVALUE on a large set of PWMs representing transcription factor binding sites. Experimental results show that it achieves better performance in terms of computational time and precision than existing tools.</p

Structural and Content Diversity of Mitochondrial Genome in Beet: A Comparative Genomic Analysis

Despite their monophyletic origin, mitochondrial (mt) genomes of plants and animals have developed contrasted evolutionary paths over time. Animal mt genomes are generally small, compact, and exhibit high mutation rates, whereas plant mt genomes exhibit low mutation rates, little compactness, larger sizes, and highly rearranged structures. We present the (nearly) whole sequences of five new mt genomes in the Beta genus: four from Beta vulgaris and one from B. macrocarpa, a sister species belonging to the same Beta section. We pooled our results with two previously sequenced genomes of B. vulgaris and studied genome diversity at the species level with an emphasis on cytoplasmic male-sterilizing (CMS) genomes. We showed that, contrary to what was previously assumed, all three CMS genomes belong to a single sterile lineage. In addition, the CMSs seem to have undergone an acceleration of the rates of substitution and rearrangement. This study suggests that male sterility emergence might have been favored by faster rates of evolution, unless CMS itself caused faster evolution

Management and outcomes of myelomeningocele-associated hydrocephalus in low-income and middle-income countries: a systematic review and meta-analysis protocol

Introduction: Hydrocephalus and myelomeningocele (MMC) place disproportionate burdens of disease on low-income and middle-income countries (LMICs). MMC-associated hydrocephalus and its sequelae result in a spectrum of severely devastating clinical manifestations, for which LMICs are disproportionately unprepared in terms of human, capital and technological resources. This study aims to review and compare the management and outcomes of infant MMC-associated hydrocephalus in LMICs and high-income countries. Methods and analysis: This systematic review and meta-analysis will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. The following databases will be searched without restrictions on language, publication date or country of origin: EMBASE, MEDLINE, The Cochrane Library, Global Index Medicus, African Journals Online and SciELO. All peer-reviewed studies of primary data reporting management and outcomes of infant MMC-associated hydrocephalus will be included. Where high-quality homogeneous studies exist, meta-analyses will be conducted to compare the management and outcomes of MMC-associated hydrocephalus across socioeconomic and geographical regions of the world. The primary outcome will be treatment failure of the first-line hydrocephalus treatment, which we defined operationally as the performance of a second intervention for the same reason as the first. Secondary outcomes include time to failure, rates of mortality and postoperative complications. Ethics and dissemination: Ethical approval was not applicable because this study does not involve human participants. Dissemination strategies will include publication in a peer-reviewed journal, oral and poster presentations at conferences and an interactive web application to facilitate interaction with the findings and promote the discussion and sharing of findings on social media. PROSPERO registration number: CRD42021285850