192 research outputs found

    Can a Week Make a Difference? Changing Perceptions about Teaching and Living in Rural Alaska

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    Many Alaskan schools are located in extremely remote or \u27fly-in\u27 places. These geographical extremes affect the recruitment and retention of teachers to remote rural schools. Through a partnership between the Southwest Region School District of Alaska and the Department of Education at Alaska Pacific University (APU), 14 pre-service teachers participated in a one-week remote rural practice teaching experience. These APU students lived and taught in village schools where indigenous Alaska Natives were the majority and whose language is Yup’ik. Through the use of pre and post experience questionnaires, the pre-service teachers’ views about rural teaching and seeking rural appointments were sought

    A multi-compartment model for interneurons in the dorsal lateral geniculate nucleus

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    GABAergic interneurons (INs) in the dorsal lateral geniculate nucleus (dLGN) shape the information flow from retina to cortex, presumably by controlling the number of visually evoked spikes in geniculate thalamocortical (TC) neurons, and refining their receptive field. The INs exhibit a rich variety of firing patterns: Depolarizing current injections to the soma may induce tonic firing, periodic bursting or an initial burst followed by tonic spiking, sometimes with prominent spike-time adaptation. When released from hyperpolarization, some INs elicit rebound bursts, while others return more passively to the resting potential. A full mechanistic understanding that explains the function of the dLGN on the basis of neuronal morphology, physiology and circuitry is currently lacking. One way to approach such an understanding is by developing a detailed mathematical model of the involved cells and their interactions. Limitations of the previous models for the INs of the dLGN region prevent an accurate representation of the conceptual framework needed to understand the computational properties of this region. We here present a detailed compartmental model of INs using, for the first time, a morphological reconstruction and a set of active dendritic conductances constrained by experimental somatic recordings from INs under several different current-clamp conditions. The model makes a number of experimentally testable predictions about the role of specific mechanisms for the firing properties observed in these neurons. In addition to accounting for the significant features of all experimental traces, it quantitatively reproduces the experimental recordings of the action-potential- firing frequency as a function of injected current. We show how and why relative differences in conductance values, rather than differences in ion channel composition, could account for the distinct differences between the responses observed in two different neurons, suggesting that INs may be individually tuned to optimize network operation under different input conditions

    Regional sociocultural differences as important correlate of physical activity and sedentary behaviour in Swiss preschool children.

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    Regional differences in physical activity in school-aged children and adults even within one country with the same political and health care system have been observed and could not be explained by sociodemographic or individual variables. We analysed whether such differences were already present in preschool children. Swiss children from 84 childcare centres in five cantons (Aargau, Bern, Fribourg, Vaud, Zurich) comprising about 50% of the population of the country participated. Physical activity was quantified with accelerometers (ActiGraph, wGT3X-BT) and potential correlates were assessed with measurements at the childcare centre or questionnaires. Mixed regression models were used to test associations between potential correlates of total physical activity (TPA), moderate-to-vigorous physical activity (MVPA), light physical activity (LPA) or sedentary behaviour with a special focus on regional differences. 394 of 476 children (83%) provided valid physical activity data (at least 2 weekdays and 1 weekend day with 10 h recording; mean age 3.9 ± 0.7 years, 54% boys) with 26% and 74% living in the French- and German-speaking parts of Switzerland, respectively. Days consisted of (mean ± standard deviation) 1.5 ± 0.5 h MVPA, 5.0 ± 0.6 h LPA, and 6.3 ± 0.8 h sedentary behaviour with an average of 624 ± 150 counts/min TPA. TPA and MVPA (but not sedentary behaviour or LPA) increased with age, were higher in boys and children with better motor skills. Despite controlling for individual characteristics, familial factors and childcare exposure, children from the French-speaking part of Switzerland showed 13% less TPA, 14% less MVPA, 6% less LPA and 8% more sedentary behaviour than German-speaking children. Beside motor skills and non-modifiable individual factors, the regional sociocultural difference was the most important correlate of phyical activity and sedentary behaviour. Therefore, regionally adapted public health strategies may be needed

    Correlates of preschool children's objectively measured physical activity and sedentary behavior: a cross-sectional analysis of the SPLASHY study.

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    Identifying ways to promote physical activity and decrease sedentary time during childhood is a key public health issue. Research on the putative influences on preschool children's physical activity (PA) and sedentary behavior (SB) is limited and has yielded inconsistent results. Our aim was to identify correlates of PA and SB in preschool children. Cross-sectional data were drawn from the Swiss Preschoolers' Health Study (SPLASHY), a Swiss population-based cohort study. Of 476 two to six year old children, 394 (54% boys) had valid PA data assessed by accelerometry. Information on exposure data was directly measured or extracted from parental questionnaires. Multilevel linear regression modeling was used to separately assess associations between 35 potential correlates and total PA (TPA), moderate-to-vigorous PA (MVPA) and SB. In total, 12 correlates from different domains were identified. TPA and MVPA were greater in boys than girls, increased with age and were positively associated with gross motor skills. Children from single parent families had a higher level of TPA and spent less time sedentary than those living with two parents. Time spent outdoors was positively associated with TPA and negatively with SB. The child's activity temperament was related all three outcomes, whereas parental sports club membership, living area per person and neighborhood safety were associated with SB only. Fixed and random factors in the final models accounted for 28%, 32% and 22% of the total variance in TPA, MVPA and SB, respectively. Variance decomposition revealed that age, sex and activity temperament were the most influential correlates of both, TPA and MVPA, whereas the child's activity temperament, time outdoors and neighborhood safety were identified as the most important correlates of SB. A multidimensional set of correlates of young children's activity behavior has been identified. Personal factors had the greatest influence on PA, whereas environmental-level factors had the greatest influence on SB. Moreover, we identified a number of previously unreported, potentially modifiable correlates of young children's PA and SB. These factors could serve to define target groups or become valuable targets for change in future interventions. Current Controlled Trials ISRCTN41045021 (date of registration: 21.03.14)

    Cytotoxic CD8+ T cell-neuron interactions: perforin-dependent electrical silencing precedes but is not causally linked to neuronal cell death

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    Cytotoxic CD8(+) T cells are considered important effector cells contributing to neuronal damage in inflammatory and degenerative CNS disorders. Using time-lapse video microscopy and two-photon imaging in combination with whole-cell patch-clamp recordings, we here show that major histocompatibility class I (MHC I)-restricted neuronal antigen presentation and T cell receptor specificity determine CD8(+) T-cell locomotion and neuronal damage in culture and hippocampal brain slices. Two separate functional consequences result from a direct cell-cell contact between antigen-presenting neurons and antigen-specific CD8(+) T cells. (1) An immediate impairment of electrical signaling in single neurons and neuronal networks occurs as a result of massive shunting of the membrane capacitance after insertion of channel-forming perforin (and probably activation of other transmembrane conductances), which is paralleled by an increase of intracellular Ca(2+) levels (within <10 min). (2) Antigen-dependent neuronal apoptosis may occur independently of perforin and members of the granzyme B cluster (within approximately 1 h), suggesting that extracellular effects can substitute for intracellular delivery of granzymes by perforin. Thus, electrical silencing is an immediate consequence of MHC I-restricted interaction of CD8(+) T cells with neurons. This mechanism is clearly perforin-dependent and precedes, but is not causally linked, to neuronal cell death

    p21Waf1 expression is regulated by nuclear intermediate filament vimentin in neuroblastoma

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    <p>Abstract</p> <p>Background</p> <p>Human neuroblastoma (NB) cell lines may present with either one of the so-called S-and N-subtypes. We have previously reported a strong correlation between protein expression levels of vimentin, an S-subtype marker, and the p21<sup>Waf1 </sup>cyclin-dependent kinase inhibitor. We here investigated whether this correlation extend to the mRNA level in NB cell lines as well as in patients' tumors. We also further explored the relationship between expression of vimentin and p21, by asking whether vimentin could regulate p21 expression.</p> <p>Methods</p> <p>Vimentin and p21 mRNA levels in NB cell lines as well as in patients' tumors (<it>n </it>= 77) were quantified using Q-PCR. Q-PCR data obtained from tumors of high risk NB patients (<it>n </it>= 40) were analyzed in relation with the overall survival using the Log-rank Kaplan-Meier estimation. siRNA-mediated depletion or overexpression of vimentin in highly or low expressing vimentin cell lines, respectively, followed by protein expression and promoter activation assays were used to assess the role of vimentin in modulating p21 expression.</p> <p>Results</p> <p>We extend the significant correlation between vimentin and p21 expression to the mRNA level in NB cell lines as well as in patients' tumors. Overall survival analysis from Q-PCR data obtained from tumors of high risk patients suggests that lower levels of p21 expression could be associated with a poorer outcome. Our data additionally indicate that the correlation observed between p21 and vimentin expression levels results from p21 transcriptional activity being regulated by vimentin. Indeed, downregulating vimentin resulted in a significant decrease in p21 mRNA and protein expression as well as in p21 promoter activity. Conversely, overexpressing vimentin triggered an increase in p21 promoter activity in cells with a nuclear expression of vimentin.</p> <p>Conclusion</p> <p>Our results suggest that p21 mRNA tumor expression level could represent a refined prognostic factor for high risk NB patients. Our data also show that vimentin regulates p21 transcription; this is the first demonstration of a gene regulating function for this type III-intermediate filament.</p

    Room temperature, continuous wave lasing in microcylinder and microring quantum dot laser diodes

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    This content may be downloaded for personal use only. Any other use requires prior permission of the author and AIP Publishing. This material originally appeared in Appl. Phys. Lett. 100, 031111 (2012) and may be found at https://doi.org/10.1063/1.3678031.We demonstrate room temperature, continuous wave lasing of laser diodes based on AlGaAs whispering gallery mode (WGM) resonators (microcylinder and microring) embedding a quantum dot (QD) active layer. Using InGaAlAs QDs, high-Q (>60 000) lasing modes are observed around 910 nm, up to 50 °C. Lasing with similar performance is obtained around 1230 nm, using InAs QDs. Furthermore, we show that the current injection in the active part of the device is improved in ring resonators, leading to threshold currents of approximately 4 mA for a device with 80 μm diameter. This geometry also suppresses WGMs with a high radial order, thus simplifying the lasing spectra. In these conditions, stable single-mode and two-color lasing can be obtained.EC/FP7/250056/EU/Terahertz room-temperature integrated parametric source/TREASUR

    Anapole nanolasers for mode-locking and ultrafast pulse generation

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    Nanophotonics is a rapidly developing field of research with many suggestions for a design of nanoantennas, sensors and miniature metadevices. Despite many proposals for passive nanophotonic devices, the efficient coupling of light to nanoscale optical structures remains a major challenge. In this article, we propose a nanoscale laser based on a tightly confined anapole mode. By harnessing the non-radiating nature of the anapole state, we show how to engineer nanolasers based on InGaAs nanodisks as on-chip sources with unique optical properties. Leveraging on the near-field character of anapole modes, we demonstrate a spontaneously polarized nanolaser able to couple light into waveguide channels with four orders of magnitude intensity than classical nanolasers, as well as the generation of ultrafast (of 100 fs) pulses via spontaneous mode locking of several anapoles. Anapole nanolasers offer an attractive platform for monolithically integrated, silicon photonics sources for advanced and efficient nanoscale circuitry

    Neuropeptide S-Mediated Facilitation of Synaptic Transmission Enforces Subthreshold Theta Oscillations within the Lateral Amygdala

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    The neuropeptide S (NPS) receptor system modulates neuronal circuit activity in the amygdala in conjunction with fear, anxiety and the expression and extinction of previously acquired fear memories. Using in vitro brain slice preparations of transgenic GAD67-GFP (Δneo) mice, we investigated the effects of NPS on neural activity in the lateral amygdala as a key region for the formation and extinction of fear memories. We are able to demonstrate that NPS augments excitatory glutamatergic synaptic input onto both projection neurons and interneurons of the lateral amygdala, resulting in enhanced spike activity of both types of cells. These effects were at least in part mediated by presynaptic mechanisms. In turn, inhibition of projection neurons by local interneurons was augmented by NPS, and subthreshold oscillations were strengthened, leading to their shift into the theta frequency range. These data suggest that the multifaceted effects of NPS on amygdaloid circuitry may shape behavior-related network activity patterns in the amygdala and reflect the peptide's potent activity in various forms of affective behavior and emotional memory

    Mitochondrial Fragmentation Is Involved in Methamphetamine-Induced Cell Death in Rat Hippocampal Neural Progenitor Cells

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    Methamphetamine (METH) induces neurodegeneration through damage and apoptosis of dopaminergic nerve terminals and striatal cells, presumably via cross-talk between the endoplasmic reticulum and mitochondria-dependent death cascades. However, the effects of METH on neural progenitor cells (NPC), an important reservoir for replacing neurons and glia during development and injury, remain elusive. Using a rat hippocampal NPC (rhNPC) culture, we characterized the METH-induced mitochondrial fragmentation, apoptosis, and its related signaling mechanism through immunocytochemistry, flow cytometry, and Western blotting. We observed that METH induced rhNPC mitochondrial fragmentation, apoptosis, and inhibited cell proliferation. The mitochondrial fission protein dynamin-related protein 1 (Drp1) and reactive oxygen species (ROS), but not calcium (Ca2+) influx, were involved in the regulation of METH-induced mitochondrial fragmentation. Furthermore, our results indicated that dysregulation of ROS contributed to the oligomerization and translocation of Drp1, resulting in mitochondrial fragmentation in rhNPC. Taken together, our data demonstrate that METH-mediated ROS generation results in the dysregulation of Drp1, which leads to mitochondrial fragmentation and subsequent apoptosis in rhNPC. This provides a potential mechanism for METH-related neurodegenerative disorders, and also provides insight into therapeutic strategies for the neurodegenerative effects of METH
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