Investigating the encoding of visual stimuli by forming neural circuits in the cat primary visual cortex

Contexte La connectomique, ou la cartographie des connexions neuronales, est un champ de recherche des neurosciences évoluant rapidement, promettant des avancées majeures en ce qui concerne la compréhension du fonctionnement cérébral. La formation de circuits neuronaux en réponse à des stimuli environnementaux est une propriété émergente du cerveau. Cependant, la connaissance que nous avons de la nature précise de ces réseaux est encore limitée. Au niveau du cortex visuel, qui est l’aire cérébrale la plus étudiée, la manière dont les informations se transmettent de neurone en neurone est une question qui reste encore inexplorée. Cela nous invite à étudier l’émergence des microcircuits en réponse aux stimuli visuels. Autrement dit, comment l’interaction entre un stimulus et une assemblée cellulaire est-elle mise en place et modulée? Méthodes En réponse à la présentation de grilles sinusoïdales en mouvement, des ensembles neuronaux ont été enregistrés dans la couche II/III (aire 17) du cortex visuel primaire de chats anesthésiés, à l’aide de multi-électrodes en tungstène. Des corrélations croisées ont été effectuées entre l’activité de chacun des neurones enregistrés simultanément pour mettre en évidence les liens fonctionnels de quasi-synchronie (fenêtre de ± 5 ms sur les corrélogrammes croisés corrigés). Ces liens fonctionnels dévoilés indiquent des connexions synaptiques putatives entre les neurones. Par la suite, les histogrammes peri-stimulus (PSTH) des neurones ont été comparés afin de mettre en évidence la collaboration synergique temporelle dans les réseaux fonctionnels révélés. Enfin, des spectrogrammes dépendants du taux de décharges entre neurones ou stimulus-dépendants ont été calculés pour observer les oscillations gamma dans les microcircuits émergents. Un indice de corrélation (Rsc) a également été calculé pour les neurones connectés et non connectés. Résultats Les neurones liés fonctionnellement ont une activité accrue durant une période de 50 ms contrairement aux neurones fonctionnellement non connectés. Cela suggère que les connexions entre neurones mènent à une synergie de leur inter-excitabilité. En outre, l’analyse du spectrogramme dépendant du taux de décharge entre neurones révèle que les neurones connectés ont une plus forte activité gamma que les neurones non connectés durant une fenêtre d’opportunité de 50ms. L’activité gamma de basse-fréquence (20-40 Hz) a été associée aux neurones à décharge régulière (RS) et l’activité de haute fréquence (60-80 Hz) aux neurones à décharge rapide (FS). Aussi, les neurones fonctionnellement connectés ont systématiquement un Rsc plus élevé que les neurones non connectés. Finalement, l’analyse des corrélogrammes croisés révèle que dans une assemblée neuronale, le réseau fonctionnel change selon l’orientation de la grille. Nous démontrons ainsi que l’intensité des relations fonctionnelles dépend de l’orientation de la grille sinusoïdale. Cette relation nous a amené à proposer l’hypothèse suivante : outre la sélectivité des neurones aux caractères spécifiques du stimulus, il y a aussi une sélectivité du connectome. En bref, les réseaux fonctionnels «signature » sont activés dans une assemblée qui est strictement associée à l’orientation présentée et plus généralement aux propriétés des stimuli. Conclusion Cette étude souligne le fait que l’assemblée cellulaire, plutôt que le neurone, est l'unité fonctionnelle fondamentale du cerveau. Cela dilue l'importance du travail isolé de chaque neurone, c’est à dire le paradigme classique du taux de décharge qui a été traditionnellement utilisé pour étudier l'encodage des stimuli. Cette étude contribue aussi à faire avancer le débat sur les oscillations gamma, en ce qu'elles surviennent systématiquement entre neurones connectés dans les assemblées, en conséquence d’un ajout de cohérence. Bien que la taille des assemblées enregistrées soit relativement faible, cette étude suggère néanmoins une intrigante spécificité fonctionnelle entre neurones interagissant dans une assemblée en réponse à une stimulation visuelle. Cette étude peut être considérée comme une prémisse à la modélisation informatique à grande échelle de connectomes fonctionnels.

Following instructions from working memory: Why does action at encoding and recall help?

Two experiments investigated the consequences of action at encoding and recall on the ability to follow sequences of instructions. Children aged 7–9 years recalled sequences of spoken action commands under presentation and recall conditions that either did or did not involve their physical performance. In both experiments, recall was enhanced by carrying out the instructions as they were being initially presented and also by performing them at recall. In contrast, the accuracy of instruction-following did not improve above spoken presentation alone, either when the instructions were silently read or heard by the child (Experiment 1), or when the child repeated the spoken instructions as they were presented (Experiment 2). These findings suggest that the enactment advantage at presentation does not simply reflect a general benefit of a dual exposure to instructions, and that it is not a result of their self-production at presentation. The benefits of action-based recall were reduced following enactment during presentation, suggesting that the positive effects of action at encoding and recall may have a common origin. It is proposed that the benefits of physical movement arise from the existence of a short-term motor store that maintains the temporal, spatial, and motoric features of either planned or already executed actions.

Mutations in CTC1, Encoding Conserved Telomere Maintenance Component 1, Cause Coats Plus

Coats plus is a highly pleiotropic disorder particularly affecting the eye, brain, bone and gastrointestinal tract. Here, we show that Coats plus results from mutations in CTC1, encoding conserved telomere maintenance component 1, a member of the mammalian homolog of the yeast heterotrimeric CST telomeric capping complex. Consistent with the observation of shortened telomeres in an Arabidopsis CTC1 mutant and the phenotypic overlap of Coats plus with the telomeric maintenance disorders comprising dyskeratosis congenita, we observed shortened telomeres in three individuals with Coats plus and an increase in spontaneous γH2AX-positive cells in cell lines derived from two affected individuals. CTC1 is also a subunit of the α-accessory factor (AAF) complex, stimulating the activity of DNA polymerase-α primase, the only enzyme known to initiate DNA replication in eukaryotic cells. Thus, CTC1 may have a function in DNA metabolism that is necessary for but not specific to telomeric integrity.

Applied web traffic analysis for numerical encoding of SQL Injection attack features.

SQL Injection Attack (SQLIA) remains a technique used by a computer network intruder to pilfer an organisation’s confidential data. This is done by an intruder re-crafting web form’s input and query strings used in web requests with malicious intent to compromise the security of an organisation’s confidential data stored at the back-end database. The database is the most valuable data source, and thus, intruders are unrelenting in constantly evolving new techniques to bypass the signature’s solutions currently provided in Web Application Firewalls (WAF) to mitigate SQLIA. There is therefore a need for an automated scalable methodology in the pre-processing of SQLIA features fit for a supervised learning model. However, obtaining a ready-made scalable dataset that is feature engineered with numerical attributes dataset items to train Artificial Neural Network (ANN) and Machine Leaning (ML) models is a known issue in applying artificial intelligence to effectively address ever evolving novel SQLIA signatures. This proposed approach applies numerical attributes encoding ontology to encode features (both legitimate web requests and SQLIA) to numerical data items as to extract scalable dataset for input to a supervised learning model in moving towards a ML SQLIA detection and prevention model. In numerical attributes encoding of features, the proposed model explores a hybrid of static and dynamic pattern matching by implementing a Non-Deterministic Finite Automaton (NFA). This combined with proxy and SQL parser Application Programming Interface (API) to intercept and parse web requests in transition to the back-end database. In developing a solution to address SQLIA, this model allows processed web requests at the proxy deemed to contain injected query string to be excluded from reaching the target back-end database. This paper is intended for evaluating the performance metrics of a dataset obtained by numerical encoding of features ontology in Microsoft Azure Machine Learning (MAML) studio using Two-Class Support Vector Machines (TCSVM) binary classifier. This methodology then forms the subject of the empirical evaluation.

Numerical encoding to tame SQL injection attacks.

Recent years have seen an astronomical rise in SQL Injection Attacks (SQLIAs) used to compromise the confidentiality, authentication and integrity of organisations’ databases. Intruders becoming smarter in obfuscating web requests to evade detection combined with increasing volumes of web traffic from the Internet of Things (IoT), cloud-hosted and on-premise business applications have made it evident that the existing approaches of mostly static signature lack the ability to cope with novel signatures. A SQLIA detection and prevention solution can be achieved through exploring an alternative bio-inspired supervised learning approach that uses input of labelled dataset of numerical attributes in classifying true positives and negatives. We present in this paper a Numerical Encoding to Tame SQLIA (NETSQLIA) that implements a proof of concept for scalable numerical encoding of features to a dataset attributes with labelled class obtained from deep web traffic analysis. In the numerical attributes encoding: the model leverages proxy in the interception and decryption of web traffic. The intercepted web requests are then assembled for front-end SQL parsing and pattern matching by applying traditional Non-Deterministic Finite Automaton (NFA). This paper is intended for a technique of numerical attributes extraction of any size primed as an input dataset to an Artificial Neural Network (ANN) and statistical Machine Learning (ML) algorithms implemented using Two-Class Averaged Perceptron (TCAP) and Two-Class Logistic Regression (TCLR) respectively. This methodology then forms the subject of the empirical evaluation of the suitability of this model in the accurate classification of both legitimate web requests and SQLIA payloads.

An Exploration of Auditory Brainstem Encoding of Stop Consonants in Infants and Implications for Language Outcomes

Current trends in speech-language pathology focus on early intervention as the preferred tool for promoting the best possible outcomes in children with language disorders. Neuroimaging techniques are being studied as promising tools for flagging at-risk infants. In this study, the auditory brainstem response (ABR) to the syllables /ba/ and /ga/ was examined in 41 infants between 3 and 12 months of age as a possible tool to predict language development in toddlerhood. The MacArthur-Bates Communicative Development Inventory (MCDI) was used to assess language development at 18 months of age. The current study compared the periodicity of the responses to the stop consonants and phase differences between /ba/ and /ga/ in both at-risk and low-risk groups. The study also examined whether there are correlations among ABR measures (periodicity and phase differentiation) and language development. The study found that these measures predict language development at 18 months.

Novel Mutation in the ATP-Binding Cassette Transporter A3 (ABCA3) Encoding Gene Causes Respiratory Distress Syndrome in A Term Newborn in Southwest Iran

Introduction: ABCA3 glycoprotein belongs to the ATP-binding cassette (ABC) superfamily of transporters, which utilize the energy derived from hydrolysis of ATP for the translocation of a wide variety of substrates across the plasma membrane. Mutations in the ABCA3 gene are knowingly causative for fatal surfactant deficiency, particularly respiratory distress syndrome (RDS) in term babies. Case Presentation: In this study, Sanger sequencing of the whole ABCA3 gene (NCBI NM_001089) was performed in a neonatal boy with severe RDS. A homozygous mutation has been identified in the patient. Parents were heterozygous for the same missense mutation GGA > AGA at position 202 in exon 6 of the ABCA3 gene (c.604G > A; p.G202R). Furthermore, 70 normal individuals have been analyzed for the mentioned change with negative results. Conclusions: Regarding Human Genome Mutation Database (HGMD) and other literature recherche, the detected change is a novel mutation and has not been reported before. Bioinformatics mutation predicting tools prefer it as pathogenic.

Characterization of the poxAB operon encoding a class D carbapenemase in Pseudomonas aeruginosa

Pseudomonas aeruginosa is a dreaded opportunistic pathogen that causes severe and often intractable infections in immunocompromised and critically ill patients. This bacterium is also the primary cause of fatal lung infections in patients with cystic fibrosis and a leading nosocomial pathogen responsible for nearly 10% of all hospital-acquired infections. P. aeruginosa is intrinsically recalcitrant to most classes of antibiotics and has the ability to acquire additional resistance during treatment. In particular, resistance to the widely used β-lactam antibiotics is frequently mediated by the expression of AmpC, a chromosomally encoded β-lactamase that is ubiquitously found in P. aeruginosa strains. This dissertation delved into the role of a recently reported chromosomal β-lactamase in P. aeruginosa called PoxB. To date, no detailed studies have addressed the regulation of poxB expression and its contribution to β-lactam resistance in P. aeruginosa. In an effort to better understand the role of this β-lactamase, poxB was deleted from the chromosome and expressed in trans from an IPTG-inducible promoter. The loss of poxB did not affect susceptibility. However, expression in trans in the absence of ampC rendered strains more resistant to the carbapenem β-lactams. The carbapenem-hydrolyzing phenotype was enhanced, reaching intermediate and resistant clinical breakpoints, in the absence of the carbapenem-specific outer membrane porin OprD. As observed for most class D β-lactamases, PoxB was only weakly inhibited by the currently available β-lactamase inhibitors. Moreover, poxB was shown to form an operon with the upstream located poxA, whose expression in trans decreased pox promoter (Ppox) activity suggesting autoregulation. The transcriptional regulator AmpR negatively controlled Ppox activity, however no direct interaction could be demonstrated. A mariner transposon library identified genes involved in the transport of polyamines as potential regulators of pox expression. Unexpectedly, polyamines themselves were able induce resistance to carbapenems. In summary, P. aeruginosa carries a chromosomal-encoded β-lactamase PoxB that can provide resistance against the clinically relevant carbapenems despite its narrow spectrum of hydrolysis and whose activity in vivo may be regulated by polyamines.^

Effects of alcohol intoxication and encoding conditions on eyewitness memory

Several researchers have investigated the effects of alcohol on memory. Few researchers have studied the effects of alcohol on an eyewitness's recall and recognition of crime events. This study proposed to examine the effects of alcohol and viewing conditions on subjects' ability to recall information regarding a videotaped bank robbery. Thirty male and 22 female subjects participated in a 2 (consumption: alcohol v. no alcohol) x 2 (lighting: good v. poor) factorial experiment with Average Accuracy and Total Amount of Information recalled as the primary dependent measures. There was no significant difference between the Intoxicated and Sober subjects regarding the amount of information recalled or their average accuracy. The main effect for lighting conditions and gender differences were also not significant.

Convergent bioenergetic defects in Coenzyme Q10 depleted cells by pharmacological inhibition of coq2 enzyme (p-hydroxybenzoate polyprenyl transferase) and by genome editing technology targeting the encoding gene (COQ2)

Primary CoQ10 deficiency diseases encompass a heterogeneous spectrum of clinical phenotypes. Among these, defect or mutation on COQ2 gene, encoding a para-hydroxybenzoate polyprenyl transferase, have been associated with different diseases. Understanding the functional and metabolic impact of COQ2 mutation and the consequent CoQ10 deficiency is still a matter of debate. To date the aetiology of the neurological phenotypes correlated to CoQ10 deficiency does not present a clear genotype-phenotype association. In addition to the metabolic alterations due to Coenzyme Q depletion, the impairment of mitochondrial function, associated with the reduced CoQ level, could play a significant role in the metabolic flexibility of cancer. This study aimed to characterize the effect of varying degrees of CoQ10 deficiency and investigate the multifaceted aspect of CoQ10 depletion and its impact on cell metabolism. To induced CoQ10 depletion, different cell models were used, employing a chemical and genome editing approach. In T67 and MCF-7 CoQ10 depletion was achieved by a competitive inhibitor of the enzyme, 4-nitrobenzoate (4-NB), whereas in SH-SY5Y the COQ2 gene was edited via CRISPR-Cas9 cutting edge technology.

Uncovering the encoding and transmission of behaviourally relevant information in neural activity

Most cognitive functions require the encoding and routing of information across distributed networks of brain regions. Information propagation is typically attributed to physical connections existing between brain regions, and contributes to the formation of spatially correlated activity patterns, known as functional connectivity. While structural connectivity provides the anatomical foundation for neural interactions, the exact manner in which it shapes functional connectivity is complex and not yet fully understood. Additionally, traditional measures of directed functional connectivity only capture the overall correlation between neural activity, and provide no insight on the content of transmitted information, limiting their ability in understanding neural computations underlying the distributed processing of behaviorally-relevant variables. In this work, we first study the relationship between structural and functional connectivity in simulated recurrent spiking neural networks with spike timing dependent plasticity. We use established measures of time-lagged correlation and overall information propagation to infer the temporal evolution of synaptic weights, showing that measures of dynamic functional connectivity can be used to reliably reconstruct the evolution of structural properties of the network. Then, we extend current methods of directed causal communication between brain areas, by deriving an information-theoretic measure of Feature-specific Information Transfer (FIT) quantifying the amount, content and direction of information flow. We test FIT on simulated data, showing its key properties and advantages over traditional measures of overall propagated information. We show applications of FIT to several neural datasets obtained with different recording methods (magneto and electro-encephalography, spiking activity, local field potentials) during various cognitive functions, ranging from sensory perception to decision making and motor learning. Overall, these analyses demonstrate the ability of FIT to advance the investigation of communication between brain regions, uncovering the previously unaddressed content of directed information flow.

Two-component System Vicrk Regulates Functions Associated With Establishment Of Streptococcus Sanguinis In Biofilms.

Streptococcus sanguinis is a commensal pioneer colonizer of teeth and an opportunistic pathogen of infectious endocarditis. The establishment of S. sanguinis in host sites likely requires dynamic fitting of the cell wall in response to local stimuli. In this study, we investigated the two-component system (TCS) VicRK in S. sanguinis (VicRKSs), which regulates genes of cell wall biogenesis, biofilm formation, and virulence in opportunistic pathogens. A vicK knockout mutant obtained from strain SK36 (SKvic) showed slight reductions in aerobic growth and resistance to oxidative stress but an impaired ability to form biofilms, a phenotype restored in the complemented mutant. The biofilm-defective phenotype was associated with reduced amounts of extracellular DNA during aerobic growth, with reduced production of H2O2, a metabolic product associated with DNA release, and with inhibitory capacity of S. sanguinis competitor species. No changes in autolysis or cell surface hydrophobicity were detected in SKvic. Reverse transcription-quantitative PCR (RT-qPCR), electrophoretic mobility shift assays (EMSA), and promoter sequence analyses revealed that VicR directly regulates genes encoding murein hydrolases (SSA_0094, cwdP, and gbpB) and spxB, which encodes pyruvate oxidase for H2O2 production. Genes previously associated with spxB expression (spxR, ccpA, ackA, and tpK) were not transcriptionally affected in SKvic. RT-qPCR analyses of S. sanguinis biofilm cells further showed upregulation of VicRK targets (spxB, gbpB, and SSA_0094) and other genes for biofilm formation (gtfP and comE) compared to expression in planktonic cells. This study provides evidence that VicRKSs regulates functions crucial for S. sanguinis establishment in biofilms and identifies novel VicRK targets potentially involved in hydrolytic activities of the cell wall required for these functions.

Reduced Plasma Angiotensin Ii Levels Are Reversed By Hydroxyurea Treatment In Mice With Sickle Cell Disease.

Sickle cell disease (SCD) pathogenesis leads to recurrent vaso-occlusive and hemolytic processes, causing numerous clinical complications including renal damage. As vasoconstrictive mechanisms may be enhanced in SCD, due to endothelial dysfunction and vasoactive protein production, we aimed to determine whether the expression of proteins of the renin-angiotensin system (RAS) may be altered in an animal model of SCD. Plasma angiotensin II (Ang II) was measured in C57BL/6 (WT) mice and mice with SCD by ELISA, while quantitative PCR was used to compare the expressions of the genes encoding the angiotensin-II-receptors 1 and 2 (AT1R and AT2R) and the angiotensin-converting enzymes (ACE1 and ACE2) in the kidneys, hearts, livers and brains of mice. The effects of hydroxyurea (HU; 50-75mg/kg/day, 4weeks) treatment on these parameters were also determined. Plasma Ang II was significantly diminished in SCD mice, compared with WT mice, in association with decreased AT1R and ACE1 expressions in SCD mice kidneys. Treatment of SCD mice with HU reduced leukocyte and platelet counts and increased plasma Ang II to levels similar to those of WT mice. HU also increased AT1R and ACE2 gene expression in the kidney and heart. Results indicate an imbalanced RAS in an SCD mouse model; HU therapy may be able to restore some RAS parameters in these mice. Further investigations regarding Ang II production and the RAS in human SCD may be warranted, as such changes may reflect or contribute to renal damage and alterations in blood pressure.

New Fefe-hydrogenase Genes Identified In A Metagenomic Fosmid Library From A Municipal Wastewater Treatment Plant As Revealed By High-throughput Sequencing.

A fosmid metagenomic library was constructed with total community DNA obtained from a municipal wastewater treatment plant (MWWTP), with the aim of identifying new FeFe-hydrogenase genes encoding the enzymes most important for hydrogen metabolism. The dataset generated by pyrosequencing of a fosmid library was mined to identify environmental gene tags (EGTs) assigned to FeFe-hydrogenase. The majority of EGTs representing FeFe-hydrogenase genes were affiliated with the class Clostridia, suggesting that this group is the main hydrogen producer in the MWWTP analyzed. Based on assembled sequences, three FeFe-hydrogenase genes were predicted based on detection of the L2 motif (MPCxxKxxE) in the encoded gene product, confirming true FeFe-hydrogenase sequences. These sequences were used to design specific primers to detect fosmids encoding FeFe-hydrogenase genes predicted from the dataset. Three identified fosmids were completely sequenced. The cloned genomic fragments within these fosmids are closely related to members of the Spirochaetaceae, Bacteroidales and Firmicutes, and their FeFe-hydrogenase sequences are characterized by the structure type M3, which is common to clostridial enzymes. FeFe-hydrogenase sequences found in this study represent hitherto undetected sequences, indicating the high genetic diversity regarding these enzymes in MWWTP. Results suggest that MWWTP have to be considered as reservoirs for new FeFe-hydrogenase genes.

Isolation of extraintestinal pathogenic Escherichia coli from diarrheic dogs and their antimicrobial resistance profile

From January to December 2006, 92 Escherichia coli isolates from 25 diarrheic dogs were analyzed by screening for the presence of adhesin-encoding genes (pap, sfa, afa), hemolysin and aerobactin genes. Virulence gene frequencies detected in those isolates were: 12% pap, 1% sfa, 10% hemolysin and 6.5% aerobactin. Ten isolates were characterized as extraintestinal pathogenic E. coli (ExPEC) strains; all showed a multidrug resistance phenotype that may represent a reason for concern due the risk of dissemination of antimicrobial resistant genes to the microbiota of human beings.