The Correlation between Sleep and Creativity

Fredrich August von Kekule, a famous German chemist, was attempting to determine the shape of the benzene molecule, which was known to have six carbon atoms. In 1865, reflecting upon his discovery of the hexagonal-ring like structure, he asserted that the solution came to him in a dream1; however, it is not clear if he was in rapid eye movement (REM) sleep dreaming or if he was in non-REM (NREM) sleep imagery. It is possible to think of this type of discoveries as an expression of creativity, i.e. the ability to use existing pieces of information and combine them in novel patterns leading to greater understanding and new solutions. Preliminary support of the role of sleep in creative thinking comes from a recent study by Wagner et al.2; these authors asked normal participants to perform a cognitive task, the Number Reduction Task. In this task, participants are required to understand a set of stimulus-response sequences and supply a single representative numerical answer. Improvement in task performance may be gradual (i.e., by slowly increasing response speed), or abrupt (after insight into an abstract rule underlying all sequences). They found that 59% of the participants that were allowed to sleep were able to perform the task in a time that was 70% shorter than the other group that did not sleep and suggested that sleep may facilitate insight-related problem solving. Here we report the results of the first study showing a direct complex correlation between sleep architecture or microstructure and creativity in normal controls

Gap filling of the CALYPSO HF radar sea surface current data through past measurements and satellite wind observations

High frequency (HF) radar installations are becoming essential components of operational real-time marine monitoring systems. The underlying technology is being further enhanced to fully exploit the potential of mapping sea surface currents and wave fields over wide areas with high spatial and temporal resolution, even in adverse meteo-marine conditions. Data applications are opening to many different sectors, reaching out beyond research and monitoring, targeting downstream services in support to key national and regional stakeholders. In the CALYPSO project, the HF radar system composed of CODAR SeaSonde stations installed in the Malta Channel is specifically serving to assist in the response against marine oil spills and to support search and rescue at sea. One key drawback concerns the sporadic inconsistency in the spatial coverage of radar data which is dictated by the sea state as well as by interference from unknown sources that may be competing with transmissions in the same frequency band. This work investigates the use of Machine Learning techniques to fill in missing data in a high resolution grid. Past radar data and wind vectors obtained from satellites are used to predict missing information and provide a more consistent dataset.peer-reviewe

Phenotyping dividing cells in mouse models of neurodegenerative basal ganglia diseases

BACKGROUND: Mice generated by a Cre/LoxP transgenic paradigm were used to model neurodegenerative basal ganglia disease of which Huntington disease (HD) is the prototypical example. In HD, death occurs in striatal projection neurons as well as cortical neurons. Cortical and striatal neurons that express the D1 dopamine receptor (Drd1a) degenerate in HD. The contribution that death of specific neuronal cell populations makes to the HD disease phenotype and the response of the brain to loss of defined cell subtypes is largely unknown. METHODS: Drd1a-expressing cells were targeted for cell death and three independent lines generated; a striatal-restricted line, a cortical-restricted line and a global line in which Drd1a cells were deleted from both the striatum and cortex. Two independent experimental approaches were used. In the first, the proliferative marker Ki-67 was used to identify proliferating cells in eighty-week-old mice belonging to a generic global line, a global in which Drd1a cells express green fluorescent protein (GFP-global) and in eighty-week-old mice of a cortical line. In the second experiment, the proliferative response of four-week-old mice belonging to GFP-global and striatal lines was assessed using the thymidine analogue BrdU. The phenotype of proliferating cells was ascertained by double staining for BrdU and Olig2 (an oligodendrocyte marker), Iba1 (a microglial cell marker), S100β (an astroglial cell marker), or NeuN (a neuronal cell marker). RESULTS: In the first study, we found that Ki-67-expressing cells were restricted to the striatal side of the lateral ventricles. Control mice had a greater number of Ki-67+ cells than mutant mice. There was no overlap between Ki-67 and GFP staining in control or mutant mice, suggesting that cells did not undergo cell division once they acquired a Drd1a phenotype. In contrast, in the second study we found that BrdU+ cells were identified throughout the cortex, striatum and periventricular region of control and mutant mice. Mutant mice from the GFP-global line showed increased BrdU+ cells in the cortex, striatum and periventricular region relative to control. Striatal line mutant mice had an increased number of BrdU+ cells in the striatum and periventricular region, but not the cortex. The number of microglia, astrocytes, oligodendrocytes and neurons generated from dividing progenitors was increased relative to control mice in most brain regions in mutant mice from the GFP-global line. In contrast, striatal line mutant mice displayed an increase only in the number of dividing microglia in striatal and periventricular regions. CONCLUSIONS: Genetically programmed post-natal ablation of Drd1a-expressing neurons is associated with an extensive proliferative response involving multiple cell lineages. The nature of the tissue response has the potential not only to remove cellular debris but also to forge physiologically meaningful brain repair. Age related deficits in proliferation are seen in mutant lines. A blunted endogenous reparative response may underlie the cumulative deficits characteristic of age related neurodegeneration

Design and development of novel screen-printed microelectrode and microbiosensor arrays fabricated using ultrafast pulsed laser ablation

© 2016 Elsevier B.V. All rights reserved. A new generic platform for the development of microbiosensors combining screen-printing and ultrafast pulsed laser technologies has been developed, characterised and evaluated. This new platform consists of a layer of screen-printed carbon ink containing the enzyme and mediator, covered with an insulating layer formed from a dielectric screen printed ink. Microholes were drilled through the insulated layer by ultrafast pulsed laser ablation to generate the microbiosensor array. The geometry of the microelectrode array was evaluated by optical microscopy, white light surface profiling and scanning electron microscopy. The electrochemical behaviour of the microelectrode array was characterised by cyclic voltammetry and compared with macroelectrodes. The analytical performance of the microbiosensor array was evaluated with external counter and reference electrodes for hydrogen peroxide and glucose determination showing linearity up to 4 mmol L-1 and 20 mmol L-1 (360 mg dL-1) respectively. The full screen printed three-electrode configuration shows linearity for glucose determination up to 20 mmol L-1 (360 mg dL-1). This study provides a new fabrication method for microelectrode and microbiosensor arrays capable for the first time to retain the activity of the enzymatic system after processing by pulse laser ablation

Dopamine D1 vs D5 receptor-dependent induction of seizures in relation to DARPP-32, ERK1/2 and GluR1-AMPA signalling.

Recent reports have shown that the selective dopamine D(1)-like agonist SKF 83822 [which stimulates adenylate cyclase, but not phospholipase C] induces prominent behavioral seizures in mice, whereas its benzazepine congener SKF 83959 [which stimulates phospholipase C, but not adenylate cyclase] does not. To investigate the relative involvement of D(1) vs D(5) receptors in mediating seizures, ethological behavioral topography and cortical EEGs were recorded in D(1), D(5) and DARPP-32 knockout mice in response to a convulsant dose of SKF 83822. SKF 83822-induced behavioral and EEG seizures were gene dose-dependently abolished in D(1) knockouts. In both heterozygous and homozygous D(5) knockouts, the latency to first seizure was significantly increased and total EEG seizures were reduced relative to wild-types. The majority (60%) of homozygous DARPP-32 knockouts did not have seizures; of those having seizures (40%), the latency to first seizure was significantly increased and the number of high amplitude, high frequency polyspike EEG events was reduced. In addition, immunoblotting was performed to investigate downstream intracellular signalling mechanisms at D(1)-like receptors following challenge with SKF 83822 and SKF 83959. In wild-types administered SKF 83822, levels of ERK1/2 and GluR1 AMPA receptor phosphorylation increased two-fold in both the striatum and hippocampus; in striatal slices DARPP-32 phosphorylation at Thr34 increased five-fold relative to vehicle-treated controls. These findings indicate that D(1), and to a lesser extent D(5), receptor coupling to DARPP-32, ERK1/2 and glutamatergic signalling is involved in mediating the convulsant effects of SKF 83822

On the Possibility of Superluminal Neutrino Propagation

We analyze the possibility of superluminal neutrino propagation delta v = (v - c)/c > 0 as indicated by OPERA data, in view of previous phenomenological constraints from supernova SN1987a and gravitational Cerenkov radiation. We argue that the SN1987a data rule out delta v ~ (E_\nu/M_N)^N for N \le 2 and exclude, in particular, a Lorentz-invariant interpretation in terms of a 'conventional' tachyonic neutrino. We present two toy Lorentz-violating theoretical models, one a Lifshitz-type fermion model with superluminality depending quadratically on energy, and the other a Lorentz-violating modification of a massless Abelian gauge theory with axial-vector couplings to fermions. In the presence of an appropriate background field, fermions may propagate superluminally or subluminally, depending inversely on energy, and on direction. Reconciling OPERA with SN1987a would require this background field to depend on location.Comment: 15 pages, replacement has an expanded and revised version of the second model; Notes added on how this model evades the Cohen-Glashow constraint

Fabrication and evaluation of a micro(bio)sensor array chip for multiple parallel measurements of important cell biomarkers

© 2014 by the authors; licensee MDPI, Basel, Switzerland. This report describes the design and development of an integrated electrochemical cell culture monitoring system, based on enzyme-biosensors and chemical sensors, for monitoring indicators of mammalian cell metabolic status. MEMS technology was used to fabricate a microwell-format silicon platform including a thermometer, onto which chemical sensors (pH, O2) and screen-printed biosensors (glucose, lactate), were grafted/deposited. Microwells were formed over the fabricated sensors to give 5-well sensor strips which were interfaced with a multipotentiostat via a bespoke connector box interface. The operation of each sensor/biosensor type was examined individually, and examples of operating devices in five microwells in parallel, in either potentiometric (pH sensing) or amperometric (glucose biosensing) mode are shown. The performance characteristics of the sensors/biosensors indicate that the system could readily be applied to cell culture/toxicity studies

Simultaneous absence of dopamine D1 and D2 receptor-mediated signaling is lethal in mice

Dopamine (DA) controls a wide variety of physiological functions in the central nervous system as well as in the neuroendocrine and gastrointestinal systems. DA signaling is mediated by five cloned receptors named D1-D5. Knockout mouse models for the five receptors have been generated, and, albeit impaired for some important DA-mediated functions, they are viable and can reproduce. D1 and D2 receptors are the most abundant and widely expressed DA receptors. Cooperative/synergistic effects mediated by these receptors have been suggested, in particular, in the control of motor behaviors. To analyze the extent of such interrelationship, we have generated double D1/D2 receptor mutants. Interestingly, in contrast to single knockouts, we found that concurrent ablation of the D1 and D2 receptors is lethal during the second or third week after birth. This dramatic phenotype is likely to be related to altered feeding behavior and dysfunction of the gastrointestinal system, especially because major anatomical changes were not identified in the brain. Similarly, in the absence of functional D1, heterozygous D2 mutants (D1r -/-;D2r +/-) showed severe growth retardation and did not survive their postweaning period. The analysis of motor behavior in D1r/D2r compound mutants showed that loss of D2-mediated functions reduces motor abilities, whereas the effect of D1r ablation on locomotion strongly depends on the experimental paradigms used. These studies highlight the interrelationship between D1 and D2 receptor-mediated control of motor activity, food intake, and gastrointestinal functions, which has been elusive in the single-gene ablation studies