Age-associated modulations of cerebral oscillatory patterns related to attention control.

Visual attention depends on bottom-up sensory activation and top-down attentional guidance. Although aging is known to affect sensory processing, its impact on the top-down control of attention remains a matter of debate. We investigated age-related modulations of brain oscillatory activity during visual attention using a variant of the attention network test (ANT) in 20 young and 28 elderly adults. We examined the EEG oscillatory responses to warning and target signals, and explored the correlates of temporal and spatial orienting as well as conflict resolution at target presentation. Time-frequency analysis was performed between 4 and 30Hz, and the relationship between behavioral and brain oscillatory responses was analyzed. Whereas temporal cueing and conflict had similar reaction time effects in both age groups, spatial cueing was more beneficial to older than younger subjects. In the absence of cue, posterior alpha activation was drastically reduced in older adults, pointing to an age-related decline in anticipatory attention. Following both cues and targets, older adults displayed pronounced motor-related activation in the low beta frequency range at the expense of attention-related posterior alpha activation prominent in younger adults. These findings support the recruitment of alternative motor-related circuits in the elderly, in line with the dedifferentiation hypothesis. Furthermore, older adults showed reduced midparietal alpha inhibition induced by temporal orienting as well as decreased posterior alpha activation associated with both spatial orienting and conflict resolution. Altogether, the results are consistent with an overall reduction of task-related alpha activity in the elderly, and provide functional evidence that younger and older adults engage distinct brain circuits at different oscillatory frequencies during attentional functions.

Perineuronal nets protect fast-spiking interneurons against oxidative stress.

A hallmark of schizophrenia pathophysiology is the dysfunction of cortical inhibitory GABA neurons expressing parvalbumin, which are essential for coordinating neuronal synchrony during various sensory and cognitive tasks. The high metabolic requirements of these fast-spiking cells may render them susceptible to redox dysregulation and oxidative stress. Using mice carrying a genetic redox imbalance, we demonstrate that extracellular perineuronal nets, which constitute a specialized polyanionic matrix enwrapping most of these interneurons as they mature, play a critical role in the protection against oxidative stress. These nets limit the effect of genetically impaired antioxidant systems and/or excessive reactive oxygen species produced by severe environmental insults. We observe an inverse relationship between the robustness of the perineuronal nets around parvalbumin cells and the degree of intracellular oxidative stress they display. Enzymatic degradation of the perineuronal nets renders mature parvalbumin cells and fast rhythmic neuronal synchrony more susceptible to oxidative stress. In parallel, parvalbumin cells enwrapped with mature perineuronal nets are better protected than immature parvalbumin cells surrounded by less-condensed perineuronal nets. Although the perineuronal nets act as a protective shield, they are also themselves sensitive to excess oxidative stress. The protection might therefore reflect a balance between the oxidative burden on perineuronal net degradation and the capacity of the system to maintain the nets. Abnormal perineuronal nets, as observed in the postmortem patient brain, may thus underlie the vulnerability and functional impairment of pivotal inhibitory circuits in schizophrenia.

Bridging the Gap: establishing the necessary infrastructure and knowledge for teaching and research in neuroscience in Africa.

Advances in neuroscience research over the last few decades have increased our understanding of how individual neurons acquire their specific properties and assemble into complex circuits, and how these circuits are affected in disease. One of the important motives driving neuroscience research is the development of new scientific techniques and interdisciplinary cooperation. Compared to developed countries, many countries on the African continent are confronted with poor facilities, lack of funding or career development programs for neuroscientists, all of which deter young scientists from taking up neuroscience as a career choice. This article highlights some steps that are being taken to promote neuroscience education and research in Africa.

Tunable reporter signal production in feedback-uncoupled arsenic bioreporters.

Escherichia coli-based bioreporters for arsenic detection are typically based on the natural feedback loop that controls ars operon transcription. Feedback loops are known to show a wide range linear response to the detriment of the overall amplification of the incoming signal. While being a favourable feature in controlling arsenic detoxification for the cell, a feedback loop is not necessarily the most optimal for obtaining highest sensitivity and response in a designed cellular reporter for arsenic detection. Here we systematically explore the effects of uncoupling the topology of arsenic sensing circuitry on the developed reporter signal as a function of arsenite concentration input. A model was developed to describe relative ArsR and GFP levels in feedback and uncoupled circuitry, which was used to explore new ArsR-based synthetic circuits. The expression of arsR was then placed under the control of a series of constitutive promoters, which differed in promoter strength, and which could be further modulated by TetR repression. Expression of the reporter gene was maintained under the ArsR-controlled Pars promoter. ArsR expression in the systems was measured by using ArsR-mCherry fusion proteins. We find that stronger constitutive ArsR production decreases arsenite-dependent EGFP output from Pars and vice versa. This leads to a tunable series of arsenite-dependent EGFP outputs in a variety of systematically characterized circuitries. The higher expression levels and sensitivities of the response curves in the uncoupled circuits may be useful for improving field-test assays using arsenic bioreporters.

Temporo-Parietal Junction encodes the Embodied Self: Neuro-Robotics, fMRI, and Lesion mapping.

Introduction: Neuroimaging of the self focused on high-level mechanisms such as language, memory or imagery of the self. Recent evidence suggests that low-level mechanisms of multisensory and sensorimotor integration may play a fundamental role in encoding self-location and the first-person perspective (Blanke and Metzinger, 2009). Neurological patients with out-of body experiences (OBE) suffer from abnormal self-location and the first-person perspective due to a damage in the temporo-parietal junction (Blanke et al., 2004). Although self-location and the first-person perspective can be studied experimentally (Lenggenhager et al., 2009), the neural underpinnings of self-location have yet to be investigated. To investigate the brain network involved in self-location and first-person perspective we used visuo-tactile multisensory conflict, magnetic resonance (MR)-compatible robotics, and fMRI in study 1, and lesion analysis in a sample of 9 patients with OBE due to focal brain damage in study 2. Methods: Twenty-two participants saw a video showing either a person's back or an empty room being stroked (visual stimuli) while the MR-compatible robotic device stroked their back (tactile stimulation). Direction and speed of the seen stroking could either correspond (synchronous) or not (asynchronous) to those of the seen stroking. Each run comprised the four conditions according to a 2x2 factorial design with Object (Body, No-Body) and Synchrony (Synchronous, Asynchronous) as main factors. Self-location was estimated using the mental ball dropping (MBD; Lenggenhager et al., 2009). After the fMRI session participants completed a 6-item adapted from the original questionnaire created by Botvinick and Cohen (1998) and based on questions and data obtained by Lenggenhager et al. (2007, 2009). They were also asked to complete a questionnaire to disclose the perspective they adopted during the illusion. Response times (RTs) for the MBD and fMRI data were analyzed with a 3-way mixed model ANOVA with the in-between factor Perspective (up, down) and the two with-in factors Object (body, no-body) and Stroking (synchronous, asynchronous). Quantitative lesion analysis was performed using MRIcron (Rorden et al., 2007). We compared the distributions of brain lesions confirmed by multimodality imaging (Knowlton, 2004) in patients with OBE with those showing complex visual hallucinations involving people or faces, but without any disturbance of self-location and first person perspective. Nine patients with OBE were investigated. The control group comprised 8 patients. Structural imaging data were available for normalization and co-registration in all the patients. Normalization of each patient's lesion into the common MNI (Montreal Neurological Institute) reference space permitted simple, voxel-wise, algebraic comparisons to be made. Results: Even if in the scanner all participants were lying on their back and were facing upwards, analysis of perspective showed that half of the participants had the impression to be looking down at the virtual human body below them, despite any cues about their body position (Down-group). The other participants had the impression to be looking up at the virtual body above them (Up-group). Analysis of Q3 ("How strong was the feeling that the body you saw was you?") indicated stronger self-identification with the virtual body during the synchronous stroking. RTs in the MBD task confirmed these subjective data (significant 3-way interaction between perspective, object and stroking). fMRI results showed eight cortical regions where the BOLD signal was significantly different during at least one of the conditions resulting from the combination of Object and Stroking, relative to baseline: right and left temporo-parietal junction, right EBA, left middle occipito-temporal gyrus, left postcentral gyrus, right medial parietal lobe, bilateral medial occipital lobe (Fig 1). The activation patterns in right and left temporo-parietal junction and right EBA reflected changes in self-location and perspective as revealed by statistical analysis that was performed on the percentage of BOLD change with respect to the baseline. Statistical lesion overlap comparison (using nonparametric voxel based lesion symptom mapping) with respect to the control group revealed the right temporo-parietal junction, centered at the angular gyrus (Talairach coordinates x = 54, y =-52, z = 26; p>0.05, FDR corrected). Conclusions: The present questionnaire and behavioural results show that - despite the noisy and constraining MR environment) our participants had predictable changes in self-location, self-identification, and first-person perspective when robotic tactile stroking was applied synchronously with the robotic visual stroking. fMRI data in healthy participants and lesion data in patients with abnormal self-location and first-person perspective jointly revealed that the temporo-parietal cortex especially in the right hemisphere encodes these conscious experiences. We argue that temporo-parietal activity reflects the experience of the conscious "I" as embodied and localized within bodily space.

Temporo-parietal cortex encodes location of the self: joining fMRI with neuroscience robotics to study bodily self-consciousness

Neuroimaging of the self has focused on high-level mechanisms such as language, memory or imagery of the self and implicated widely distributed brain networks. Yet recent evidence suggests that low-level mechanisms such as multisensory and sensorimotor integration may play a fundamental role in self-related processing. In the present study we used visuotactile multisensory conflict, robotics, virtual reality, and fMRI to study such low-level mechanisms by experimentally inducing changes in self-location. Participants saw a video of a person's back (body) or an empty room (no-body) being stroked while a MR-compatible robotic device stroked their back. The latter tactile input was synchronous or asynchronous with respect to the seen stroking. Self-location was estimated behaviorally confirming previous data that self-location only differed between the two body conditions. fMRI results showed a bilateral activation of the temporo-parietal cortex with a significantly higher BOLD signal increase in the synchronous/body condition with respect to the other conditions. Sensorimotor cortex and extrastriate-body-area were also activated. We argue that temporo-parietal activity reflects the experience of the conscious 'I' as embodied and localized within bodily space, compatible with clinical data in neurological patients with out-of-body experiences.

Desarrollo de tecnología Bulk Acoustic Wave

El creciente uso de dispositivos móviles y el gran avance en la mejora de las aplicaciones y sistemas inalámbricos ha impulsado la demanda de filtros paso banda miniaturizados, que trabajen a altas frecuencias y tengan unas prestaciones elevadas. Los filtros basados en resonadores Bulk Acoustic Wave (BAW) están siendo la mejor alternativa a los filtros Surface Acoustic Wave (SAW), ya que funcionan a frecuencias superiores, pueden trabajar a mayores niveles de potencia y son compatibles con la tecnología CMOS. El filtro en escalera, que utiliza resonadores BAW, es de momento la mejor opción, debido a su facilidad de diseño y su bajo coste de fabricación. Aunque el filtro con resonadores acoplados (CRF) presenta mejores prestaciones como mayor ancho de banda, menor tamaño y conversión de modos. El problema de este tipo de filtros reside en su complejidad de diseño y su elevado coste. Este trabajo lleva a cabo el diseño de un CRF a partir de unas especificaciones bastante estrictas, demostrando sus altas prestaciones a pesar de su mayor inconveniente: el coste de fabricación.

Avoiding transcription factor competition at promoter level increases the chances of obtaining oscillations

Background: The ultimate goal of synthetic biology is the conception and construction of genetic circuits that are reliable with respect to their designed function (e.g. oscillators, switches). This task remains still to be attained due to the inherent synergy of the biological building blocks and to an insufficient feedback between experiments and mathematical models. Nevertheless, the progress in these directions has been substantial. Results: It has been emphasized in the literature that the architecture of a genetic oscillator must include positive (activating) and negative (inhibiting) genetic interactions in order to yield robust oscillations. Our results point out that the oscillatory capacity is not only affected by the interaction polarity but by how it is implemented at promoter level. For a chosen oscillator architecture, we show by means of numerical simulations that the existence or lack of competition between activator and inhibitor at promoter level affects the probability of producing oscillations and also leaves characteristic fingerprints on the associated period/amplitude features. Conclusions: In comparison with non-competitive binding at promoters, competition drastically reduces the region of the parameters space characterized by oscillatory solutions. Moreover, while competition leads to pulse-like oscillations with long-tail distribution in period and amplitude for various parameters or noisy conditions, the non-competitive scenario shows a characteristic frequency and confined amplitude values. Our study also situates the competition mechanism in the context of existing genetic oscillators, with emphasis on the Atkinson oscillator.

Hypothalamus transcriptome profile suggests an anorexia-cachexia syndrome in the anx/anx mouse model

The anx/anx mouse displays poor appetite and lean appearance and is considered a good model for the study of anorexia nervosa. To identify new genes involved in feeding behavior and body weight regulation we performed an expression profiling in the hypothalamus of the anx/anx mice. Using commercial microarrays we detected 156 differentially expressed genes and validated 92 of those using TaqMan low-density arrays. The expression of a set of 87 candidate genes selected based on literature evidences was also quantified by TaqMan low-density arrays. Our results showed enrichment in deregulated genes involved in cell death, cell morphology and cancer as well as an alteration of several signaling circuits involved in energy balance including neuropeptide Y and melanocortin signaling. The expression profile along with the phenotype led us to conclude that anx/anx mice resemble the anorexia-cachexia syndrome typically observed in cancer, infection with human immunodeficiency virus or chronic diseases, rather than starvation, and that anx/anx mice could be considered a good model for the treatment and investigation of this condition.

Cannabinoid addiction: behavioral models and neural correlates

The use of cannabis sativa preparations as recreational drugs can be traced back to the earliest civilizations. However, animal models of cannabinoid addiction allowing the exploration of neural correlates of cannabinoid abuse have been developed only recently. We review these models and the role of the CB1 cannabinoid receptor, the main target of natural cannabinoids, and its interaction with opioid and dopamine transmission in reward circuits. Extensive reviews on the molecular basis of cannabinoid action are available elsewhere (Piomelli et al., 2000;Schlicker and Kathmann, 2001).

An Investigation of User Costs and Benefits of Winter Road Closures, June 2005

This project explores the user costs and benefits of winter road closures. Severe winter weather makes travel unsafe and dramatically increases crash rates. When conditions become unsafe due to winter weather, road closures should allow users to avoid crash costs and eliminate costs associated with rescuing stranded motorists. Therefore, the benefits of road closures are the avoided safety costs. The costs of road closures are the delays that are imposed on motorists and motor carriers who would have made the trip had the road not been closed. This project investigated the costs and benefits of road closures and found that evaluating the benefits and costs is not as simple as it appears. To better understand the costs and benefits of road closures, the project investigates the literature, conducts interviews with shippers and motor carriers, and conducts case studies of road closures to determine what actually occurred on roadways during closures. The project also estimates a statistical model that relates weather severity to crash rates. Although, the statistical model is intended to illustrate the possibility to quantitatively relate measurable and predictable weather conditions to the safety performance of a roadway. In the future, weather conditions such as snow fall intensity, visibility, etc., can be used to make objective measures of the safety performance of a roadway rather than relying on subjective evaluations of field staff. The review of the literature and the interviews clearly illustrate that not all delays (increased travel time) are valued the same. Expected delays (routine delays) are valued at the generalized costs (value of the driver’s time, fuel, insurance, wear and tear on the vehicle, etc.), but unexpected delays are valued much higher because they result in interruption of synchronous activities at the trip’s destination. To reduce the costs of delays resulting from road closures, public agencies should communicate as early as possible the likelihood of a road closure.

Oxytocin selectively gates fear responses through distinct outputs from the central amygdala.

Central amygdala (CeA) projections to hypothalamic and brain stem nuclei regulate the behavioral and physiological expression of fear, but it is unknown whether these different aspects of the fear response can be separately regulated by the CeA. We combined fluorescent retrograde tracing of CeA projections to nuclei that modulate fear-related freezing or cardiovascular responses with in vitro electrophysiological recordings and with in vivo monitoring of related behavioral and physiological parameters. CeA projections emerged from separate neuronal populations with different electrophysiological characteristics and different response properties to oxytocin. In vivo, oxytocin decreased freezing responses in fear-conditioned rats without affecting the cardiovascular response. Thus, neuropeptidergic signaling can modulate the CeA outputs through separate neuronal circuits and thereby individually steer the various aspects of the fear response.

Early Cretaceous radiolarians of the Northeast Indian Ocean (leg 123 - site 765, site 766 and dsdp site 261) - The Antarctic-Tethys connection

During ODP Leg 123, abundant and well-preserved Neocomian radiolarians were recovered at Site 765 (Argo Abyssal Plain) and Site 766 (lower Exmouth Plateau). Assemblages are characterized by the numerical dominance of a small number of non-tethyan forms and by the scarcity of tethyan taxa. Remarkable contrasts exist between radiolarian assemblages extracted from claystones of Site 765 and reexamined DSDP Site 26 1, and faunas recovered from radiolarian sand layers, only found at Site 765. Clay faunas are unusual in their low diversity of apparently ecologically tolerant (or solution resistant?), ubiquist species, whereas sand faunas are dominated by non-tethyan taxa. Comparisons with Sites 766 and 26 1, as well as sedimentological observations, lead to the conclusion that this faunal contrast resulted from a difference in provenance, rather than from hydraulic sorting or selective dissolution. The ranges of 27 tethyan taxa from Site 765 were compared to the tethyan radiolarian zonation by Jud (1992) by means of the Unitary Associations Method. This calculation allows to directly date the Site 765 assemblages and to estimate the amount of truncation of ranges for tethyan taxa. Over 70% of the already few tethyan species of Site 765, have truncated ranges during the Valanginian-Hauterivian. Radiolarian assemblages recovered from claystones at Sites 765 and 261 in the Argo Basin apparently reflect restricted oceanic conditions during the latest Jurassic-Barremian. Neither sedimentary facies nor faunal associations bear any resemblance to what we know from typical tethyan sequences. We conclude that the Argo Basin was paleoceanographically separated from the Tethys during the Late Jurassic and part of the Early Cretaceous by its position at higher paleolatitudes and/or by enclosing land masses. Assemblages recovered from radiolarian sand layers are dominated by non-tethyan species that are interpreted as circumantarctic. Their first appearance in the late Berriasian-early Valanginian predates the oceanization of the Indo-Australian breakup (M11, late Valanginian), but coincides with a sharp increase in margin-derived pelagic turbidites. The Indo-Australian rift zone and the adjacent margins must have been submerged deeply enough to allow an intermittent influx of circumantarctic cold water into the Argo Basin, creating increased bottom current activity. Cold-water radiolarians carried into the Argo Basin upwelled along the margin, died, and accumulated in radiolarite layers due to winnowing by bottom currents. High rates of faunal change and the sharp increase of bottom current activity are thought to be synchronous with possible pronounced late Berriasian-early Valanginian lowstands in sea level. Hypothetically, both phenomena might have been.caused by a tendency to glaciation on the Antarctic-Australian continent, which was for the first time isolated from the rest of Gondwana by oceanic seaways as a result of Jurassic-Early Cretaceous sea-floor spreading. The absence of most typical tethyan radiolarian species during the Valanginian-Hauterivian is interpreted as reflecting a time of strong influx of circumantarctic cold water following oceanization (M11) and rapid spreading between Southeast India and West Australia. The reappearance and gradual abundance/diversity increase of tethyan taxa, along with the still dominant circumantarctic species are thought to result from overall more equitable climatic conditions during the Barremian-early Aptian and from the establishment of an oceanic connection with the Tethys Ocean during the early Aptian.

Sähkökoneen staattorikäämityksen kehittäminen

Tämä insinöörityö tehtiin ABB:n Pitäjänmäen konetehtaalle Tahtikoneet-tulosyksikölle. Työssä tutkittiin mahdollisuuksia valmistaa murtovakovyyhtejä kestomagneettituuligeneraattoreihin, joissa vakoluku on alle yhden. Työ tehtiin tutustumalla aluksi Pitäjänmäen konetehtaan käytössä oleviin vyyhden valmistus- ja käämintämenetelmiin. Lisäksi tutkittiin erilaisia mahdollisia murtovakovyyhden valmistusmenetelmiä, joista lupaavimpia myös kokeiltiin. Saatujen kokemusten pohjalta valittiin vyyhden valmistusmenetelmä, jonka mukaan valmistettiin koe-erä. Koe-erälle suoritettiin mittauksia, joilla varmistettiin niiden sähköinen kestävyys Työn tuloksena valitulla valmistusmenetelmällä valmistettiin vyyhdet prototyyppi tuuligeneraattorin.

Symmetristen komponenttien mallinnus

Tässä insinöörityössä suunniteltiin Helsingin ammattikorkeakoululle jakeluverkoissa tapahtuvien oikosulkujen symmetristen komponenttien laskutavan havainnollistamiseen sopiva sijaiskytkentä. Sijaiskytkennässä tärkeitä huomioitavia asioita olivat mm. jännitetaso, havainnollistavien muuntajien oikosulkukestoisuus, jatkokäyttö laboratoriotyönä ja yleinen havainnollistavuus. Työssä on aluksi perehdytty symmetristen komponenttien ja jakeluverkoissa tapahtuvien oikosulkujen teoriaan. Tämän jälkeen mitoitettiin tarvittavan kytkennän komponenttien jännite- ja virtakestoisuudet mahdolliset lisäkäytöt huomioiden. Näiden rajoitusten mukaan perusteella työtä ruvettiin toteuttamaan. Työssä tilattiin sähkön 40 V:n pääjännitetasolle alentava muuntaja syöttämään oikosulun kestävää muuntajaa, jolla simuloitiin jakeluverkon yleisimpiä vikatyyppejä. Jälkimmäiselle muuntajalle mitoitettiin ja hankittiin sisäistä impedanssia vastaava induktanssi. Tämän avulla rakennettiin kokonaisuus, jonka avulla voidaan simuloida kaikkia tapahtuvia oikosulkuja vastaavat sijaiskytkennät. Työhön jätettiin kehittämisvaraa ja muita laboratoriotyön rakentamismahdollisuuksia tulevien insinööritöiden tekijöille.