Neuronal gap junctions play a role in the secondary neuronal death following controlled cortical impact.

PubMed

Belousov, Andrei B; Wang, Yongfu; Song, Ji-Hoon; Denisova, Janna V; Berman, Nancy E; Fontes, Joseph D

2012-08-22

In the mammalian CNS, excessive release of glutamate and overactivation of glutamate receptors are responsible for the secondary (delayed) neuronal death following neuronal injury, including ischemia, traumatic brain injury (TBI) and epilepsy. Recent studies in mice showed a critical role for neuronal gap junctions in NMDA receptor-mediated excitotoxicity and ischemia-mediated neuronal death. Here, using controlled cortical impact (CCI) in adult mice, as a model of TBI, and Fluoro-Jade B staining for analysis of neuronal death, we set to determine whether neuronal gap junctions play a role in the CCI-mediated secondary neuronal death. We report that 24h post-CCI, substantial neuronal death is detected in a number of brain regions outside the injury core, including the striatum. The striatal neuronal death is reduced both in wild-type mice by systemic administration of mefloquine (a relatively selective blocker of neuronal gap junctions) and in knockout mice lacking connexin 36 (neuronal gap junction protein). It is also reduced by inactivation of group II metabotropic glutamate receptors (with LY341495) which, as reported previously, control the rapid increase in neuronal gap junction coupling following different types of neuronal injury. The results suggest that neuronal gap junctions play a critical role in the CCI-induced secondary neuronal death. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Paradoxical response preceding control of Scedosporium apiospermum mycetoma with posaconazole treatment.

PubMed

Béraud, Guillaume; Desbois, Nicole; Coyo, Caroline; Quist, Danièle; Rozé, Benoit; Savorit, Luc; Cabié, André

2015-01-01

Mycetoma is a chronic granulomatous infection that is difficult to treat, notably when due to fungi such as Scedosporium apiospermum. Recent antifungal agents could be an option, but cases are rarely reported, and none with posaconazole. Paradoxical responses, defined as initial clinical worsening despite appropriate treatment, are common in tuberculosis but rare in deep mycoses in non-immunocompromised hosts. Hence, paradoxical responses in context other than mycobacterial infection in an immunocompromised host could provide insights into the pathophysiology and the optimal strategy for treatment. We report the first case of a mycetoma caused by S. apiospermum with bone involvement treated with posaconazole, and the paradoxical response observed at the beginning of the treatment. As with mycobacterial infections, a paradoxical response in deep mycosis could represent the earliest marker of therapeutic efficacy.

Melanin-concentrating hormone neurons discharge in a reciprocal manner to orexin neurons across the sleep–wake cycle

PubMed Central

Hassani, Oum Kaltoum; Lee, Maan Gee; Jones, Barbara E.

2009-01-01

Neurons containing melanin-concentrating hormone (MCH) are codistributed with neurons containing orexin (Orx or hypocretin) in the lateral hypothalamus, a peptide and region known to be critical for maintaining wakefulness. Evidence from knockout and c-Fos studies suggests, however, that the MCH neurons might play a different role than Orx neurons in regulating activity and sleep–wake states. To examine this possibility, neurons were recorded across natural sleep–wake states in head-fixed rats and labeled by using the juxtacellular technique for subsequent immunohistochemical identification. Neurons identified as MCH+ did not fire during wake (W); they fired selectively during sleep, occasionally during slow wave sleep (SWS) and maximally during paradoxical sleep (PS). As W-Off/Sleep-On, the MCH neurons discharged in a reciprocal manner to the W-On/Sleep-Off Orx neurons and could accordingly play a complementary role to Orx neurons in sleep–wake state regulation and contribute to the pathophysiology of certain sleep disorders, such as narcolepsy with cataplexy. PMID:19188611

Beyond Parrondo's Paradox

PubMed Central

SHU, Jian-Jun; WANG, Qi-Wen

2014-01-01

The Parrondo's paradox is a counterintuitive phenomenon where individually-losing strategies can be combined in producing a winning expectation. In this paper, the issues surrounding the Parrondo's paradox are investigated. The focus is lying on testifying whether the same paradoxical effect can be reproduced by using a simple capital dependent game. The paradoxical effect generated by the Parrondo's paradox can be explained by placing all the parameters in one probability space. Based on this framework, it is able to generate other possible paradoxical effects by manipulating the parameters in the probability space. PMID:24577586

Temperature influences neuronal activity and CO2/pH sensitivity of locus coeruleus neurons in the bullfrog, Lithobates catesbeianus.

PubMed

Santin, Joseph M; Watters, Kayla C; Putnam, Robert W; Hartzler, Lynn K

2013-12-15

The locus coeruleus (LC) is a chemoreceptive brain stem region in anuran amphibians and contains neurons sensitive to physiological changes in CO2/pH. The ventilatory and central sensitivity to CO2/pH is proportional to the temperature in amphibians, i.e., sensitivity increases with increasing temperature. We hypothesized that LC neurons from bullfrogs, Lithobates catesbeianus, would increase CO2/pH sensitivity with increasing temperature and decrease CO2/pH sensitivity with decreasing temperature. Further, we hypothesized that cooling would decrease, while warming would increase, normocapnic firing rates of LC neurons. To test these hypotheses, we used whole cell patch-clamp electrophysiology to measure firing rate, membrane potential (V(m)), and input resistance (R(in)) in LC neurons in brain stem slices from adult bullfrogs over a physiological range of temperatures during normocapnia and hypercapnia. We found that cooling reduced chemosensitive responses of LC neurons as temperature decreased until elimination of CO2/pH sensitivity at 10°C. Chemosensitive responses increased at elevated temperatures. Surprisingly, chemosensitive LC neurons increased normocapnic firing rate and underwent membrane depolarization when cooled and decreased normocapnic firing rate and underwent membrane hyperpolarization when warmed. These responses to temperature were not observed in nonchemosensitive LC neurons or neurons in a brain stem slice 500 μm rostral to the LC. Our results indicate that modulation of cellular chemosensitivity within the LC during temperature changes may influence temperature-dependent respiratory drive during acid-base disturbances in amphibians. Additionally, cold-activated/warm-inhibited LC neurons introduce paradoxical temperature sensitivity in respiratory control neurons of amphibians.

YADCLAN: yet another digitally-controlled linear artificial neuron.

PubMed

Frenger, Paul

2003-01-01

This paper updates the author's 1999 RMBS presentation on digitally controlled linear artificial neuron design. Each neuron is based on a standard operational amplifier having excitatory and inhibitory inputs, variable gain, an amplified linear analog output and an adjustable threshold comparator for digital output. This design employs a 1-wire serial network of digitally controlled potentiometers and resistors whose resistance values are set and read back under microprocessor supervision. This system embodies several unique and useful features, including: enhanced neuronal stability, dynamic reconfigurability and network extensibility. This artificial neuronal is being employed for feature extraction and pattern recognition in an advanced robotic application.

Native intra- and inter-specific reactions may cause the paradox of pest control with harvesting.

PubMed

Seno, Hiromi

2010-05-01

We analyse a general time-discrete mathematical model of host-parasite population dynamics with harvesting, in which the host can be regarded as a pest. We harvest a portion of the host population at a moment in each year. Our model involves the density effect on the host population. We investigate the condition in which the harvesting of the host results in a paradoxical increase of its equilibrium population size. Our results imply that for a family of pest-enemy systems, the paradox of pest control could be caused essentially by the interspecific relationship and the intraspecific density effect.

Regulatory Mechanisms Controlling Maturation of Serotonin Neuron Identity and Function

PubMed Central

Spencer, William C.; Deneris, Evan S.

2017-01-01

The brain serotonin (5-hydroxytryptamine; 5-HT) system has been extensively studied for its role in normal physiology and behavior, as well as, neuropsychiatric disorders. The broad influence of 5-HT on brain function, is in part due to the vast connectivity pattern of 5-HT-producing neurons throughout the CNS. 5-HT neurons are born and terminally specified midway through embryogenesis, then enter a protracted period of maturation, where they functionally integrate into CNS circuitry and then are maintained throughout life. The transcriptional regulatory networks controlling progenitor cell generation and terminal specification of 5-HT neurons are relatively well-understood, yet the factors controlling 5-HT neuron maturation are only recently coming to light. In this review, we first provide an update on the regulatory network controlling 5-HT neuron development, then delve deeper into the properties and regulatory strategies governing 5-HT neuron maturation. In particular, we discuss the role of the 5-HT neuron terminal selector transcription factor (TF) Pet-1 as a key regulator of 5-HT neuron maturation. Pet-1 was originally shown to positively regulate genes needed for 5-HT synthesis, reuptake and vesicular transport, hence 5-HT neuron-type transmitter identity. It has now been shown to regulate, both positively and negatively, many other categories of genes in 5-HT neurons including ion channels, GPCRs, transporters, neuropeptides, and other transcription factors. Its function as a terminal selector results in the maturation of 5-HT neuron excitability, firing characteristics, and synaptic modulation by several neurotransmitters. Furthermore, there is a temporal requirement for Pet-1 in the control of postmitotic gene expression trajectories thus indicating a direct role in 5-HT neuron maturation. Proper regulation of the maturation of cellular identity is critical for normal neuronal functioning and perturbations in the gene regulatory networks controlling

Regulatory Mechanisms Controlling Maturation of Serotonin Neuron Identity and Function.

PubMed

Spencer, William C; Deneris, Evan S

2017-01-01

The brain serotonin (5-hydroxytryptamine; 5-HT) system has been extensively studied for its role in normal physiology and behavior, as well as, neuropsychiatric disorders. The broad influence of 5-HT on brain function, is in part due to the vast connectivity pattern of 5-HT-producing neurons throughout the CNS. 5-HT neurons are born and terminally specified midway through embryogenesis, then enter a protracted period of maturation, where they functionally integrate into CNS circuitry and then are maintained throughout life. The transcriptional regulatory networks controlling progenitor cell generation and terminal specification of 5-HT neurons are relatively well-understood, yet the factors controlling 5-HT neuron maturation are only recently coming to light. In this review, we first provide an update on the regulatory network controlling 5-HT neuron development, then delve deeper into the properties and regulatory strategies governing 5-HT neuron maturation. In particular, we discuss the role of the 5-HT neuron terminal selector transcription factor (TF) Pet-1 as a key regulator of 5-HT neuron maturation. Pet-1 was originally shown to positively regulate genes needed for 5-HT synthesis, reuptake and vesicular transport, hence 5-HT neuron-type transmitter identity. It has now been shown to regulate, both positively and negatively, many other categories of genes in 5-HT neurons including ion channels, GPCRs, transporters, neuropeptides, and other transcription factors. Its function as a terminal selector results in the maturation of 5-HT neuron excitability, firing characteristics, and synaptic modulation by several neurotransmitters. Furthermore, there is a temporal requirement for Pet-1 in the control of postmitotic gene expression trajectories thus indicating a direct role in 5-HT neuron maturation. Proper regulation of the maturation of cellular identity is critical for normal neuronal functioning and perturbations in the gene regulatory networks controlling

Prefrontal Parvalbumin Neurons in Control of Attention

PubMed Central

Kim, Hoseok; Ährlund-Richter, Sofie; Wang, Xinming; Deisseroth, Karl; Carlén, Marie

2016-01-01

Summary While signatures of attention have been extensively studied in sensory systems, the neural sources and computations responsible for top-down control of attention are largely unknown. Using chronic recordings in mice, we found that fast-spiking parvalbumin (FS-PV) interneurons in medial prefrontal cortex (mPFC) uniformly show increased and sustained firing during goal-driven attentional processing, correlating to the level of attention. Elevated activity of FS-PV neurons on the timescale of seconds predicted successful execution of behavior. Successful allocation of attention was characterized by strong synchronization of FS-PV neurons, increased gamma oscillations, and phase locking of pyramidal firing. Phase-locked pyramidal neurons showed gamma-phase-dependent rate modulation during successful attentional processing. Optogenetic silencing of FS-PV neurons deteriorated attentional processing, while optogenetic synchronization of FS-PV neurons at gamma frequencies had pro-cognitive effects and improved goal-directed behavior. FS-PV neurons thus act as a functional unit coordinating the activity in the local mPFC circuit during goal-driven attentional processing. PMID:26771492

Coordinated temporal and spatial control of motor neuron and serotonergic neuron generation from a common pool of CNS progenitors.

PubMed

Pattyn, Alexandre; Vallstedt, Anna; Dias, José M; Samad, Omar Abdel; Krumlauf, Robb; Rijli, Filippo M; Brunet, Jean-Francois; Ericson, Johan

2003-03-15

Neural progenitor cells often produce distinct types of neurons in a specific order, but the determinants that control the sequential generation of distinct neuronal subclasses in the vertebrate CNS remain poorly defined. We examined the sequential generation of visceral motor neurons and serotonergic neurons from a common pool of neural progenitors located in the ventral hindbrain. We found that the temporal specification of these neurons varies along the anterior-posterior axis of the hindbrain, and that the timing of their generation critically depends on the integrated activities of Nkx- and Hox-class homeodomain proteins. A primary function of these proteins is to coordinate the spatial and temporal activation of the homeodomain protein Phox2b, which in turn acts as a binary switch in the selection of motor neuron or serotonergic neuronal fate. These findings assign new roles for Nkx, Hox, and Phox2 proteins in the control of temporal neuronal fate determination, and link spatial and temporal patterning of CNS neuronal fates.

Coordinated temporal and spatial control of motor neuron and serotonergic neuron generation from a common pool of CNS progenitors

PubMed Central

Pattyn, Alexandre; Vallstedt, Anna; Dias, José M.; Samad, Omar Abdel; Krumlauf, Robb; Rijli, Filippo M.; Brunet, Jean-Francois; Ericson, Johan

2003-01-01

Neural progenitor cells often produce distinct types of neurons in a specific order, but the determinants that control the sequential generation of distinct neuronal subclasses in the vertebrate CNS remain poorly defined. We examined the sequential generation of visceral motor neurons and serotonergic neurons from a common pool of neural progenitors located in the ventral hindbrain. We found that the temporal specification of these neurons varies along the anterior-posterior axis of the hindbrain, and that the timing of their generation critically depends on the integrated activities of Nkx- and Hox-class homeodomain proteins. A primary function of these proteins is to coordinate the spatial and temporal activation of the homeodomain protein Phox2b, which in turn acts as a binary switch in the selection of motor neuron or serotonergic neuronal fate. These findings assign new roles for Nkx, Hox, and Phox2 proteins in the control of temporal neuronal fate determination, and link spatial and temporal patterning of CNS neuronal fates. PMID:12651891

Selection and parameterization of cortical neurons for neuroprosthetic control.

PubMed

Wahnoun, Remy; He, Jiping; Helms Tillery, Stephen I

2006-06-01

When designing neuroprosthetic interfaces for motor function, it is crucial to have a system that can extract reliable information from available neural signals and produce an output suitable for real life applications. Systems designed to date have relied on establishing a relationship between neural discharge patterns in motor cortical areas and limb movement, an approach not suitable for patients who require such implants but who are unable to provide proper motor behavior to initially tune the system. We describe here a method that allows rapid tuning of a population vector-based system for neural control without arm movements. We trained highly motivated primates to observe a 3D center-out task as the computer played it very slowly. Based on only 10-12 s of neuronal activity observed in M1 and PMd, we generated an initial mapping between neural activity and device motion that the animal could successfully use for neuroprosthetic control. Subsequent tunings of the parameters led to improvements in control, but the initial selection of neurons and estimated preferred direction for those cells remained stable throughout the remainder of the day. Using this system, we have observed that the contribution of individual neurons to the overall control of the system is very heterogeneous. We thus derived a novel measure of unit quality and an indexing scheme that allowed us to rate each neuron's contribution to the overall control. In offline tests, we found that fewer than half of the units made positive contributions to the performance. We tested this experimentally by having the animals control the neuroprosthetic system using only the 20 best neurons. We found that performance in this case was better than when the entire set of available neurons was used. Based on these results, we believe that, with careful task design, it is feasible to parameterize control systems without any overt behaviors and that subsequent control system design will be enhanced with

Stanislas Dehaene's Les Neurones de la Lecture

ERIC Educational Resources Information Center

Battro, Antonio M.

2008-01-01

Stanislas Dehaene has published a remarkable book on the neurons of reading. It is a comprehensive description of the main issues related to the "paradox of reading": how humans process linguistic information using the visual brain path while the brain has not evolved in the short period of time since the invention of writing. The article presents…

Network control principles predict neuron function in the Caenorhabditis elegans connectome

PubMed Central

Chew, Yee Lian; Walker, Denise S.; Schafer, William R.; Barabási, Albert-László

2017-01-01

Recent studies on the controllability of complex systems offer a powerful mathematical framework to systematically explore the structure-function relationship in biological, social and technological networks1–3. Despite theoretical advances, we lack direct experimental proof of the validity of these widely used control principles. Here we fill this gap by applying a control framework to the connectome of the nematode C. elegans4–6, allowing us to predict the involvement of each C. elegans neuron in locomotor behaviours. We predict that control of the muscles or motor neurons requires twelve neuronal classes, which include neuronal groups previously implicated in locomotion by laser ablation7–13, as well as one previously uncharacterised neuron, PDB. We validate this prediction experimentally, finding that the ablation of PDB leads to a significant loss of dorsoventral polarity in large body bends. Importantly, control principles also allow us to investigate the involvement of individual neurons within each neuronal class. For example, we predict that, within the class of DD motor neurons, only three (DD04, DD05, or DD06) should affect locomotion when ablated individually. This prediction is also confirmed, with single-cell ablations of DD04 or DD05, but not DD02 or DD03, specifically affecting posterior body movements. Our predictions are robust to deletions of weak connections, missing connections, and rewired connections in the current connectome, indicating the potential applicability of this analytical framework to larger and less well-characterised connectomes. PMID:29045391

Network control principles predict neuron function in the Caenorhabditis elegans connectome

NASA Astrophysics Data System (ADS)

Yan, Gang; Vértes, Petra E.; Towlson, Emma K.; Chew, Yee Lian; Walker, Denise S.; Schafer, William R.; Barabási, Albert-László

2017-10-01

Recent studies on the controllability of complex systems offer a powerful mathematical framework to systematically explore the structure-function relationship in biological, social, and technological networks. Despite theoretical advances, we lack direct experimental proof of the validity of these widely used control principles. Here we fill this gap by applying a control framework to the connectome of the nematode Caenorhabditis elegans, allowing us to predict the involvement of each C. elegans neuron in locomotor behaviours. We predict that control of the muscles or motor neurons requires 12 neuronal classes, which include neuronal groups previously implicated in locomotion by laser ablation, as well as one previously uncharacterized neuron, PDB. We validate this prediction experimentally, finding that the ablation of PDB leads to a significant loss of dorsoventral polarity in large body bends. Importantly, control principles also allow us to investigate the involvement of individual neurons within each neuronal class. For example, we predict that, within the class of DD motor neurons, only three (DD04, DD05, or DD06) should affect locomotion when ablated individually. This prediction is also confirmed; single cell ablations of DD04 or DD05 specifically affect posterior body movements, whereas ablations of DD02 or DD03 do not. Our predictions are robust to deletions of weak connections, missing connections, and rewired connections in the current connectome, indicating the potential applicability of this analytical framework to larger and less well-characterized connectomes.

Network control principles predict neuron function in the Caenorhabditis elegans connectome.

PubMed

Yan, Gang; Vértes, Petra E; Towlson, Emma K; Chew, Yee Lian; Walker, Denise S; Schafer, William R; Barabási, Albert-László

2017-10-26

Recent studies on the controllability of complex systems offer a powerful mathematical framework to systematically explore the structure-function relationship in biological, social, and technological networks. Despite theoretical advances, we lack direct experimental proof of the validity of these widely used control principles. Here we fill this gap by applying a control framework to the connectome of the nematode Caenorhabditis elegans, allowing us to predict the involvement of each C. elegans neuron in locomotor behaviours. We predict that control of the muscles or motor neurons requires 12 neuronal classes, which include neuronal groups previously implicated in locomotion by laser ablation, as well as one previously uncharacterized neuron, PDB. We validate this prediction experimentally, finding that the ablation of PDB leads to a significant loss of dorsoventral polarity in large body bends. Importantly, control principles also allow us to investigate the involvement of individual neurons within each neuronal class. For example, we predict that, within the class of DD motor neurons, only three (DD04, DD05, or DD06) should affect locomotion when ablated individually. This prediction is also confirmed; single cell ablations of DD04 or DD05 specifically affect posterior body movements, whereas ablations of DD02 or DD03 do not. Our predictions are robust to deletions of weak connections, missing connections, and rewired connections in the current connectome, indicating the potential applicability of this analytical framework to larger and less well-characterized connectomes.

Control of cortical neuronal migration by glutamate and GABA

PubMed Central

Luhmann, Heiko J.; Fukuda, A.; Kilb, W.

2015-01-01

Neuronal migration in the cortex is controlled by the paracrine action of the classical neurotransmitters glutamate and GABA. Glutamate controls radial migration of pyramidal neurons by acting primarily on NMDA receptors and regulates tangential migration of inhibitory interneurons by activating non-NMDA and NMDA receptors. GABA, acting on ionotropic GABAA-rho and GABAA receptors, has a dichotomic action on radially migrating neurons by acting as a GO signal in lower layers and as a STOP signal in upper cortical plate (CP), respectively. Metabotropic GABAB receptors promote radial migration into the CP and tangential migration of interneurons. Besides GABA, the endogenous GABAergic agonist taurine is a relevant agonist controlling radial migration. To a smaller extent glycine receptor activation can also influence radial and tangential migration. Activation of glutamate and GABA receptors causes increases in intracellular Ca2+ transients, which promote neuronal migration by acting on the cytoskeleton. Pharmacological or genetic manipulation of glutamate or GABA receptors during early corticogenesis induce heterotopic cell clusters in upper layers and loss of cortical lamination, i.e., neuronal migration disorders which can be associated with neurological or neuropsychiatric diseases. The pivotal role of NMDA and ionotropic GABA receptors in cortical neuronal migration is of major clinical relevance, since a number of drugs acting on these receptors (e.g., anti-epileptics, anesthetics, alcohol) may disturb the normal migration pattern when present during early corticogenesis. PMID:25688185

Generalized Hardy's Paradox

NASA Astrophysics Data System (ADS)

Jiang, Shu-Han; Xu, Zhen-Peng; Su, Hong-Yi; Pati, Arun Kumar; Chen, Jing-Ling

2018-01-01

Here, we present the most general framework for n -particle Hardy's paradoxes, which include Hardy's original one and Cereceda's extension as special cases. Remarkably, for any n ≥3 , we demonstrate that there always exist generalized paradoxes (with the success probability as high as 1 /2n -1) that are stronger than the previous ones in showing the conflict of quantum mechanics with local realism. An experimental proposal to observe the stronger paradox is also presented for the case of three qubits. Furthermore, from these paradoxes we can construct the most general Hardy's inequalities, which enable us to detect Bell's nonlocality for more quantum states.

Paradoxical sphincter contraction is rarely indicative of anismus

PubMed Central

Voderholzer, W; Neuhaus, D; Klauser, A; Tzavella, K; Muller-Lissner, S; Schindlbeck, N

1997-01-01

Background—Anismus is thought to be a cause of chronic constipation by producing outlet obstruction. The underlying mechanism is paradoxical contraction of the anal sphincter or puborectalis muscle. However, paradoxical sphincter contraction (PSC) also occurs in healthy controls, so anismus may be diagnosed too often because it may be based on a non-specific finding related to untoward conditions during the anorectal examination. 
Aims—To investigate the pathophysiological importance of PSC found at anorectal manometry in constipated patients and in patients with stool incontinence. 
Methods—Digital rectal examination and anorectal manometry were performed in 102 chronically constipated patients, 102 patients with stool incontinence, and in 18 controls without anorectal disease. In 120 of the 222 subjects defaecography was also performed. Paradoxical sphincter contraction was defined as a sustained increase in sphincter pressure during straining. Anismus was assumed when PSC was present on anorectal manometry and digital rectal examination and the anorectal angle did not widen on defaecography. 
Results—Manometric PSC occurred about twice as often in constipated patients as in incontinent patients (41.2% versus 25.5%, p<0.017) and its prevalence was similar in incontinent patients and controls (25.5% versus 22.2%). Oroanal or rectosigmoid transit times in constipated patients with and without PSC did not differ significantly (total 64.6 (8.9) hours versus 54.2 (8.1) hours; rectosigmoid 14.9 (2.4) hours versus 13.8 (2.5) hours). 
Conclusions—Paradoxical sphincter contraction is a common finding in healthy controls as well as in patients with chronic constipation and stool incontinence. Hence, PSC is primarily a laboratory artefact and true anismus is rare. 

 Keywords: anismus; paradoxical sphincter contraction; constipation; stool incontinence; anorectal manometry PMID:9301508

Training a Network of Electronic Neurons for Control of a Mobile Robot

NASA Astrophysics Data System (ADS)

Vromen, T. G. M.; Steur, E.; Nijmeijer, H.

An adaptive training procedure is developed for a network of electronic neurons, which controls a mobile robot driving around in an unknown environment while avoiding obstacles. The neuronal network controls the angular velocity of the wheels of the robot based on the sensor readings. The nodes in the neuronal network controller are clusters of neurons rather than single neurons. The adaptive training procedure ensures that the input-output behavior of the clusters is identical, even though the constituting neurons are nonidentical and have, in isolation, nonidentical responses to the same input. In particular, we let the neurons interact via a diffusive coupling, and the proposed training procedure modifies the diffusion interaction weights such that the neurons behave synchronously with a predefined response. The working principle of the training procedure is experimentally validated and results of an experiment with a mobile robot that is completely autonomously driving in an unknown environment with obstacles are presented.

Low excitatory innervation balances high intrinsic excitability of immature dentate neurons

PubMed Central

Dieni, Cristina V.; Panichi, Roberto; Aimone, James B.; Kuo, Chay T.; Wadiche, Jacques I.; Overstreet-Wadiche, Linda

2016-01-01

Persistent neurogenesis in the dentate gyrus produces immature neurons with high intrinsic excitability and low levels of inhibition that are predicted to be more broadly responsive to afferent activity than mature neurons. Mounting evidence suggests that these immature neurons are necessary for generating distinct neural representations of similar contexts, but it is unclear how broadly responsive neurons help distinguish between similar patterns of afferent activity. Here we show that stimulation of the entorhinal cortex in mouse brain slices paradoxically generates spiking of mature neurons in the absence of immature neuron spiking. Immature neurons with high intrinsic excitability fail to spike due to insufficient excitatory drive that results from low innervation rather than silent synapses or low release probability. Our results suggest that low synaptic connectivity prevents immature neurons from responding broadly to cortical activity, potentially enabling excitable immature neurons to contribute to sparse and orthogonal dentate representations. PMID:27095423

Predictive models of glucose control: roles for glucose-sensing neurones.

PubMed

Kosse, C; Gonzalez, A; Burdakov, D

2015-01-01

The brain can be viewed as a sophisticated control module for stabilizing blood glucose. A review of classical behavioural evidence indicates that central circuits add predictive (feedforward/anticipatory) control to the reactive (feedback/compensatory) control by peripheral organs. The brain/cephalic control is constructed and engaged, via associative learning, by sensory cues predicting energy intake or expenditure (e.g. sight, smell, taste, sound). This allows rapidly measurable sensory information (rather than slowly generated internal feedback signals, e.g. digested nutrients) to control food selection, glucose supply for fight-or-flight responses or preparedness for digestion/absorption. Predictive control is therefore useful for preventing large glucose fluctuations. We review emerging roles in predictive control of two classes of widely projecting hypothalamic neurones, orexin/hypocretin (ORX) and melanin-concentrating hormone (MCH) cells. Evidence is cited that ORX neurones (i) are activated by sensory cues (e.g. taste, sound), (ii) drive hepatic production, and muscle uptake, of glucose, via sympathetic nerves, (iii) stimulate wakefulness and exploration via global brain projections and (iv) are glucose-inhibited. MCH neurones are (i) glucose-excited, (ii) innervate learning and reward centres to promote synaptic plasticity, learning and memory and (iii) are critical for learning associations useful for predictive control (e.g. using taste to predict nutrient value of food). This evidence is unified into a model for predictive glucose control. During associative learning, inputs from some glucose-excited neurones may promote connections between the 'fast' senses and reward circuits, constructing neural shortcuts for efficient action selection. In turn, glucose-inhibited neurones may engage locomotion/exploration and coordinate the required fuel supply. Feedback inhibition of the latter neurones by glucose would ensure that glucose fluxes they stimulate

The fermi paradox is neither Fermi's nor a paradox.

PubMed

Gray, Robert H

2015-03-01

The so-called Fermi paradox claims that if technological life existed anywhere else, we would see evidence of its visits to Earth--and since we do not, such life does not exist, or some special explanation is needed. Enrico Fermi, however, never published anything on this topic. On the one occasion he is known to have mentioned it, he asked "Where is everybody?"--apparently suggesting that we do not see extraterrestrials on Earth because interstellar travel may not be feasible, but not suggesting that intelligent extraterrestrial life does not exist or suggesting its absence is paradoxical. The claim "they are not here; therefore they do not exist" was first published by Michael Hart, claiming that interstellar travel and colonization of the Galaxy would be inevitable if intelligent extraterrestrial life existed, and taking its absence here as proof that it does not exist anywhere. The Fermi paradox appears to originate in Hart's argument, not Fermi's question. Clarifying the origin of these ideas is important, because the Fermi paradox is seen by some as an authoritative objection to searching for evidence of extraterrestrial intelligence--cited in the U.S. Congress as a reason for killing NASA's SETI program on one occasion. But evidence indicates that it misrepresents Fermi's views, misappropriates his authority, deprives the actual authors of credit, and is not a valid paradox.

Low excitatory innervation balances high intrinsic excitability of immature dentate neurons

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dieni, Cristina V.; Panichi, Roberto; Aimone, James B.

Persistent neurogenesis in the dentate gyrus produces immature neurons with high intrinsic excitability and low levels of inhibition that are predicted to be more broadly responsive to afferent activity than mature neurons. Mounting evidence suggests that these immature neurons are necessary for generating distinct neural representations of similar contexts, but it is unclear how broadly responsive neurons help distinguish between similar patterns of afferent activity. Here we show that stimulation of the entorhinal cortex in mouse brain slices paradoxically generates spiking of mature neurons in the absence of immature neuron spiking. Immature neurons with high intrinsic excitability fail to spikemore » due to insufficient excitatory drive that results from low innervation rather than silent synapses or low release probability. Here, our results suggest that low synaptic connectivity prevents immature neurons from responding broadly to cortical activity, potentially enabling excitable immature neurons to contribute to sparse and orthogonal dentate representations.« less

Low excitatory innervation balances high intrinsic excitability of immature dentate neurons

DOE PAGES

Dieni, Cristina V.; Panichi, Roberto; Aimone, James B.; ...

2016-04-20

Persistent neurogenesis in the dentate gyrus produces immature neurons with high intrinsic excitability and low levels of inhibition that are predicted to be more broadly responsive to afferent activity than mature neurons. Mounting evidence suggests that these immature neurons are necessary for generating distinct neural representations of similar contexts, but it is unclear how broadly responsive neurons help distinguish between similar patterns of afferent activity. Here we show that stimulation of the entorhinal cortex in mouse brain slices paradoxically generates spiking of mature neurons in the absence of immature neuron spiking. Immature neurons with high intrinsic excitability fail to spikemore » due to insufficient excitatory drive that results from low innervation rather than silent synapses or low release probability. Here, our results suggest that low synaptic connectivity prevents immature neurons from responding broadly to cortical activity, potentially enabling excitable immature neurons to contribute to sparse and orthogonal dentate representations.« less

Paradoxical sleep as a tool for understanding the hippocampal mechanisms of contextual memory.

PubMed

Sil'kis, I G

2010-01-01

Existing data on the involvement of the hippocampus in contextual memory and the fact that contextual memory is impaired in dreams occurring during paradoxical sleep allowed us to suggest that one of the causes of this impairment consists of changes in the efficiency of synaptic transmission in the hippocampus due to increases (as compared with waking) in the concentrations of acetylcholine, dopamine, and cortisol, as well as the absence of serotonin and noradrenaline. Our previous analysis showed that in paradoxical sleep, long-term depression can be induced all components of the polysynaptic pathway through the hippocampal formation, while potentiation can occur at the inputs from the entorhinal cortex to hippocampal fields CA1 and CA3 and in the associative connections in field CA3. It is hypothesized that the correct functioning of episodic memory requires efficient transmission of signals in each component of the polysynaptic pathway through the hippocampus, allowing a neuronal representation of the context to be created within it. In the state of waking, reproduction of the context of an episode simultaneously activates the neuronal representation of the context remembered in the hippocampus and neuronal representations of the details of the episode remembered in those areas of the cortex in which they were processed. It follows from the proposed mechanism that any neurotransmitter or neuropeptide able to promote longterm potentiation in all components of the polysynaptic pathway through the hippocampus can improve episodic memory. As the consequences of the mechanism are consistent with experimental data, it can be used to seek agents improving episodic memory.

Investigating neuronal function with optically controllable proteins

PubMed Central

Zhou, Xin X.; Pan, Michael; Lin, Michael Z.

2015-01-01

In the nervous system, protein activities are highly regulated in space and time. This regulation allows for fine modulation of neuronal structure and function during development and adaptive responses. For example, neurite extension and synaptogenesis both involve localized and transient activation of cytoskeletal and signaling proteins, allowing changes in microarchitecture to occur rapidly and in a localized manner. To investigate the role of specific protein regulation events in these processes, methods to optically control the activity of specific proteins have been developed. In this review, we focus on how photosensory domains enable optical control over protein activity and have been used in neuroscience applications. These tools have demonstrated versatility in controlling various proteins and thereby cellular functions, and possess enormous potential for future applications in nervous systems. Just as optogenetic control of neuronal firing using opsins has changed how we investigate the function of cellular circuits in vivo, optical control may yet yield another revolution in how we study the circuitry of intracellular signaling in the brain. PMID:26257603

Minimal time spiking in various ChR2-controlled neuron models.

PubMed

Renault, Vincent; Thieullen, Michèle; Trélat, Emmanuel

2018-02-01

We use conductance based neuron models, and the mathematical modeling of optogenetics to define controlled neuron models and we address the minimal time control of these affine systems for the first spike from equilibrium. We apply tools of geometric optimal control theory to study singular extremals, and we implement a direct method to compute optimal controls. When the system is too large to theoretically investigate the existence of singular optimal controls, we observe numerically the optimal bang-bang controls.

Simpson's Paradox: Examples.

PubMed

Wang, Bokai; Wu, Pan; Kwan, Brian; Tu, Xin M; Feng, Changyong

2018-04-25

Simpson's paradox is very prevalent in many areas. It characterizes the inconsistency between the conditional and marginal interpretations of the data. In this paper, we illustrate through some examples how the Simpson's paradox can happen in continuous, categorical, and time-to-event data.

Paradoxical sphincter contraction is rarely indicative of anismus.

PubMed

Voderholzer, W A; Neuhaus, D A; Klauser, A G; Tzavella, K; Müller-Lissner, S A; Schindlbeck, N E

1997-08-01

Anismus is thought to be a cause of chronic constipation by producing outlet obstruction. The underlying mechanism is paradoxical contraction of the anal sphincter or puborectalis muscle. However, paradoxical sphincter contraction (PSC) also occurs in healthy controls, so anismus may be diagnosed too often because it may be based on a non-specific finding related to untoward conditions during the anorectal examination. To investigate the pathophysiological importance of PSC found at anorectal manometry in constipated patients and in patients with stool incontinence. Digital rectal examination and anorectal manometry were performed in 102 chronically constipated patients, 102 patients with stool incontinence, and in 18 controls without anorectal disease. In 120 of the 222 subjects defaecography was also performed. Paradoxical sphincter contraction was defined as a sustained increase in sphincter pressure during straining. Anismus was assumed when PSC was present on anorectal manometry and digital rectal examination and the anorectal angle did not widen on defaecography. Manometric PSC occurred about twice as often in constipated patients as in incontinent patients (41.2% versus 25.5%, p < 0.017) and its prevalence was similar in incontinent patients and controls (25.5% versus 22.2%). Oroanal or rectosigmoid transit times in constipated patients with and without PSC did not differ significantly (total 64.6 (8.9) hours versus 54.2 (8.1) hours; rectosigmoid 14.9 (2.4) hours versus 13.8 (2.5) hours). Paradoxical sphincter contraction is a common finding in healthy controls as well as in patients with chronic constipation and stool incontinence. Hence, PSC is primarily a laboratory artefact and true anismus is rare.

Multisetting Greenberger-Horne-Zeilinger paradoxes

NASA Astrophysics Data System (ADS)

Tang, Weidong; Yu, Sixia; Oh, C. H.

2017-01-01

The Greenberger-Horne-Zeilinger (GHZ) paradox provides an all-versus-nothing test for the quantum nonlocality. In most of the GHZ paradoxes known so far each observer is allowed to measure only two alternative observables. Here we present a general construction for GHZ paradoxes in which each observer measures more than two observables given that the system is prepared in the n -qudit GHZ state. By doing so we are able to construct a multisetting GHZ paradox for the n -qubit GHZ state, with n being arbitrary, which is genuine n -partite; i.e., no GHZ paradox exists when restricted to a subset of a number of observers for a given set of Mermin observables. Our result fills up the gap of the absence of a genuine GHZ paradox for the GHZ state of an even number of qubits, especially the four-qubit GHZ state as used in GHZ's original proposal.

Hunger neurons drive feeding through a sustained, positive reinforcement signal.

PubMed

Chen, Yiming; Lin, Yen-Chu; Zimmerman, Christopher A; Essner, Rachel A; Knight, Zachary A

2016-08-24

The neural mechanisms underlying hunger are poorly understood. AgRP neurons are activated by energy deficit and promote voracious food consumption, suggesting these cells may supply the fundamental hunger drive that motivates feeding. However recent in vivo recording experiments revealed that AgRP neurons are inhibited within seconds by the sensory detection of food, raising the question of how these cells can promote feeding at all. Here we resolve this paradox by showing that brief optogenetic stimulation of AgRP neurons before food availability promotes intense appetitive and consummatory behaviors that persist for tens of minutes in the absence of continued AgRP neuron activation. We show that these sustained behavioral responses are mediated by a long-lasting potentiation of the rewarding properties of food and that AgRP neuron activity is positively reinforcing. These findings reveal that hunger neurons drive feeding by transmitting a positive valence signal that triggers a stable transition between behavioral states.

Homeostatic Changes in GABA and Acetylcholine Muscarinic Receptors on GABAergic Neurons in the Mesencephalic Reticular Formation following Sleep Deprivation

PubMed Central

2017-01-01

Abstract We have examined whether GABAergic neurons in the mesencephalic reticular formation (RFMes), which are believed to inhibit the neurons in the pons that generate paradoxical sleep (PS or REMS), are submitted to homeostatic regulation under conditions of sleep deprivation (SD) by enforced waking during the day in mice. Using immunofluorescence, we investigated first, by staining for c-Fos, whether GABAergic RFMes neurons are active during SD and then, by staining for receptors, whether their activity is associated with homeostatic changes in GABAA or acetylcholine muscarinic type 2 (AChM2) receptors (Rs), which evoke inhibition. We found that a significantly greater proportion of the GABAergic neurons were positively stained for c-Fos after SD (∼27%) as compared to sleep control (SC; ∼1%) and sleep recovery (SR; ∼6%), suggesting that they were more active during waking with SD and less active or inactive during sleep with SC and SR. The density of GABAARs and AChM2Rs on the plasma membrane of the GABAergic neurons was significantly increased after SD and restored to control levels after SR. We conclude that the density of these receptors is increased on RFMes GABAergic neurons during presumed enhanced activity with SD and is restored to control levels during presumed lesser or inactivity with SR. Such increases in GABAAR and AChM2R with sleep deficits would be associated with increased susceptibility of the wake-active GABAergic neurons to inhibition from GABAergic and cholinergic sleep-active neurons and to thus permitting the onset of sleep and PS with muscle atonia. PMID:29302615

Dopaminergic Neurons Controlling Anterior Pituitary Functions: Anatomy and Ontogenesis in Zebrafish.

PubMed

Fontaine, Romain; Affaticati, Pierre; Bureau, Charlotte; Colin, Ingrid; Demarque, Michaël; Dufour, Sylvie; Vernier, Philippe; Yamamoto, Kei; Pasqualini, Catherine

2015-08-01

Dopaminergic (DA) neurons located in the preoptico-hypothalamic region of the brain exert a major neuroendocrine control on reproduction, growth, and homeostasis by regulating the secretion of anterior pituitary (or adenohypophysis) hormones. Here, using a retrograde tract tracing experiment, we identified the neurons playing this role in the zebrafish. The DA cells projecting directly to the anterior pituitary are localized in the most anteroventral part of the preoptic area, and we named them preoptico-hypophyseal DA (POHDA) neurons. During development, these neurons do not appear before 72 hours postfertilization (hpf) and are the last dopaminergic cell group to differentiate. We found that the number of neurons in this cell population continues to increase throughout life proportionally to the growth of the fish. 5-Bromo-2'-deoxyuridine incorporation analysis suggested that this increase is due to continuous neurogenesis and not due to a phenotypic change in already-existing neurons. Finally, expression profiles of several genes (foxg1a, dlx2a, and nr4a2a/b) were different in the POHDA compared with the adjacent suprachiasmatic DA neurons, suggesting that POHDA neurons develop as a distinct DA cell population in the preoptic area. This study offers some insights into the regional identity of the preoptic area and provides the first bases for future functional genetic studies on the development of DA neurons controlling anterior pituitary functions.

Fuzzy decoupling controller based on multimode control algorithm of PI-single neuron and its application

NASA Astrophysics Data System (ADS)

Zhang, Xianxia; Wang, Jian; Qin, Tinggao

2003-09-01

Intelligent control algorithms are introduced into the control system of temperature and humidity. A multi-mode control algorithm of PI-Single Neuron is proposed for single loop control of temperature and humidity. In order to remove the coupling between temperature and humidity, a new decoupling method is presented, which is called fuzzy decoupling. The decoupling is achieved by using a fuzzy controller that dynamically modifies the static decoupling coefficient. Taking the control algorithm of PI-Single Neuron as the single loop control of temperature and humidity, the paper provides the simulated output response curves with no decoupling control, static decoupling control and fuzzy decoupling control. Those control algorithms are easily implemented in singlechip-based hardware systems.

The Paradoxical Role of the Research Administrator.

ERIC Educational Resources Information Center

White, Virginia P.

1991-01-01

This reprinted 1970 article examines the role of the university research administrator and finds that the role involves paradoxes between controller and entrepreneur, master and slave, censor and publicist, and traditionalist and innovator. (DB)

The paradoxical nature of surrender.

PubMed

Holley, Dorothy E Adamson

2007-01-01

Surrender is one of the most fundamental, important aspects of spirituality and of integration. It is crucial to our relationship to God, to self, and to others. While surrender is essential for any real attempt at authenticity and integration, it is also one of the most challenging aspects of any spiritual pursuit or endeavor. The inability or unwillingness to surrender is a serious impediment to our relationship with God, with others, and even with ourselves. Paradoxically, there is great freedom and an increased sense of control that is experienced when one is able to surrender. This article explores two themes that the author believes are involved in surrender: fear and trust. Clinical as well as personal examples of the paradoxical nature and transformational power of surrender are offered.

Obesity Paradox in End-Stage Kidney Disease Patients

PubMed Central

Park, Jongha; Ahmadi, Seyed-Foad; Streja, Elani; Molnar, Miklos Z; Flegal, Katherine M.; Gillen, Daniel; Kovesdy, Csaba P.; Kalantar-Zadeh, Kamyar

2016-01-01

In the general population, obesity is associated with increased cardiovascular risk and decreased survival. In patients with end-stage renal disease (ESRD), however, an “obesity paradox” or “reverse epidemiology” (to include lipid and hypertension paradoxes) has been consistently reported, i.e. a higher body mass index (BMI) is paradoxically associated with better survival. This survival advantage of large body size is relatively consistent for hemodialysis patients across racial and regional differences, although published results are mixed for peritoneal dialysis patients.. Recent data indicate that both higher skeletal muscle mass and increased total body fat are protective, although there are mixed data on visceral (intra-abdominal) fat. The obesity paradox in ESRD is unlikely to be due to residual confounding alone and has biologic plausibility. Possible causes of the obesity paradox include protein-energy wasting and inflammation, time discrepancy among competitive risk factors (undernutrition versus overnutrition), hemodynamic stability, alteration of circulatory cytokines, sequestration of uremic toxin in adipose tissue, and endotoxin-lipoprotein interaction. The obesity paradox may have significant clinical implications in the management of ESRD patients especially if obese dialysis patients are forced to lose weight upon transplant wait-listing. Well-designed studies exploring the causes and consequences of the reverse epidemiology of cardiovascular risk factors, including the obesity paradox, among ESRD patients could provide more information on mechanisms. These could include controlled trials of nutritional and pharmacologic interventions to examine whether gain in lean body mass or even body fat can improve survival and quality of life in these patients. PMID:24438733

Planar cell polarity genes control the connectivity of enteric neurons

PubMed Central

Sasselli, Valentina; Boesmans, Werend; Vanden Berghe, Pieter; Tissir, Fadel; Goffinet, André M.; Pachnis, Vassilis

2013-01-01

A highly complex network of intrinsic enteric neurons is required for the digestive and homeostatic functions of the gut. Nevertheless, the genetic and molecular mechanisms that regulate their assembly into functional neuronal circuits are currently unknown. Here we report that the planar cell polarity (PCP) genes Celsr3 and Fzd3 are required during murine embryogenesis to specifically control the guidance and growth of enteric neuronal projections relative to the longitudinal and radial gut axes. Ablation of these genes disrupts the normal organization of nascent neuronal projections, leading to subtle changes of axonal tract configuration in the mature enteric nervous system (ENS), but profound abnormalities in gastrointestinal motility. Our data argue that PCP-dependent modules of connectivity established at early stages of enteric neurogenesis control gastrointestinal function in adult animals and provide the first evidence that developmental deficits in ENS wiring may contribute to the pathogenesis of idiopathic bowel disorders. PMID:23478408

The Simpson's paradox unraveled

PubMed Central

Hernán, Miguel A; Clayton, David; Keiding, Niels

2011-01-01

Background In a famous article, Simpson described a hypothetical data example that led to apparently paradoxical results. Methods We make the causal structure of Simpson's example explicit. Results We show how the paradox disappears when the statistical analysis is appropriately guided by subject-matter knowledge. We also review previous explanations of Simpson's paradox that attributed it to two distinct phenomena: confounding and non-collapsibility. Conclusion Analytical errors may occur when the problem is stripped of its causal context and analyzed merely in statistical terms. PMID:21454324

Pleiotrophin antagonizes Brd2 during neuronal differentiation

PubMed Central

Garcia-Gutierrez, Pablo; Juarez-Vicente, Francisco; Wolgemuth, Debra J.; Garcia-Dominguez, Mario

2014-01-01

ABSTRACT Bromodomain-containing protein 2 (Brd2) is a BET family chromatin adaptor required for expression of cell-cycle-associated genes and therefore involved in cell cycle progression. Brd2 is expressed in proliferating neuronal progenitors, displays cell-cycle-stimulating activity and, when overexpressed, impairs neuronal differentiation. Paradoxically, Brd2 is also detected in differentiating neurons. To shed light on the role of Brd2 in the transition from cell proliferation to differentiation, we had previously looked for proteins that interacted with Brd2 upon induction of neuronal differentiation. Surprisingly, we identified the growth factor pleiotrophin (Ptn). Here, we show that Ptn antagonized the cell-cycle-stimulating activity associated with Brd2, thus enhancing induced neuronal differentiation. Moreover, Ptn knockdown reduced neuronal differentiation. We analyzed Ptn-mediated antagonism of Brd2 in a cell differentiation model and in two embryonic processes associated with the neural tube: spinal cord neurogenesis and neural crest migration. Finally, we investigated the mechanisms of Ptn-mediated antagonism and determined that Ptn destabilizes the association of Brd2 with chromatin. Thus, Ptn-mediated Brd2 antagonism emerges as a modulation system accounting for the balance between cell proliferation and differentiation in the vertebrate nervous system. PMID:24695857

Differential control over postganglionic neurons in rat cardiac ganglia by NA and DmnX neurons: anatomical evidence.

PubMed

Cheng, Zixi; Zhang, Hong; Guo, Shang Z; Wurster, Robert; Gozal, David

2004-04-01

In previous single-labeling experiments, we showed that neurons in the nucleus ambiguous (NA) and the dorsal moto nucleus of the vagus (DmnX) project to intrinsic cardiac ganglia. Neurons in these two motor nuclei differ significantly in the size of their projection fields, axon caliber, and endings in cardiac ganglia. These differences in NA and DmnX axon cardiac projections raise the question as to whether they target the same, distinct, or overlapping populations of cardiac principal neurons. To address this issue, we examined vagal terminals in cardiac ganglia and trace injection sites in the brain stem using two different anterograde t ace s 1,1-dioleyl-3,3,3,3-tetramethylindocarbocyanine methanesulfonate and 4-[4-(dihexadecylamino)-styryl]-N-methylpyridinium iodide] and confocal microscopy in male Sprague-Dawley rats. We found that 1) NA and DmnX neurons innervate the same cardiac ganglia, but these axons target separate subpopulations of principal neurons and 2) axons arising from neurons in the NA and DmnX in the contralateral sides of the brain stem enter the cardiac ganglionic plexus through separate bundles and preferentially innervate principal neurons near their entry regions, providing topographic mapping of vagal motor neurons in left and right brain stem vagal nuclei. Because the NA and DmnX project to distinct populations of cardiac principal neurons, we propose that they may play different roles in controlling cardiac function.

The Paradox of Regulations: A Commentary.

ERIC Educational Resources Information Center

Taylor, Steven J.

1992-01-01

This response to previous symposium papers (EC 604 155-161) concerning regulations and quality assurance in Intermediate Care Facilities for the Mentally Retarded (ICF/MR) sees regulations as the bureaucratization of values, identifies paradoxes implicit in regulatory controls, and urges reform of the current developmental disability service…

Homeostatic Changes in GABA and Acetylcholine Muscarinic Receptors on GABAergic Neurons in the Mesencephalic Reticular Formation following Sleep Deprivation.

PubMed

Toossi, Hanieh; Del Cid-Pellitero, Esther; Jones, Barbara E

2017-01-01

We have examined whether GABAergic neurons in the mesencephalic reticular formation (RFMes), which are believed to inhibit the neurons in the pons that generate paradoxical sleep (PS or REMS), are submitted to homeostatic regulation under conditions of sleep deprivation (SD) by enforced waking during the day in mice. Using immunofluorescence, we investigated first, by staining for c-Fos, whether GABAergic RFMes neurons are active during SD and then, by staining for receptors, whether their activity is associated with homeostatic changes in GABA A or acetylcholine muscarinic type 2 (AChM2) receptors (Rs), which evoke inhibition. We found that a significantly greater proportion of the GABAergic neurons were positively stained for c-Fos after SD (∼27%) as compared to sleep control (SC; ∼1%) and sleep recovery (SR; ∼6%), suggesting that they were more active during waking with SD and less active or inactive during sleep with SC and SR. The density of GABA A Rs and AChM2Rs on the plasma membrane of the GABAergic neurons was significantly increased after SD and restored to control levels after SR. We conclude that the density of these receptors is increased on RFMes GABAergic neurons during presumed enhanced activity with SD and is restored to control levels during presumed lesser or inactivity with SR. Such increases in GABA A R and AChM2R with sleep deficits would be associated with increased susceptibility of the wake-active GABAergic neurons to inhibition from GABAergic and cholinergic sleep-active neurons and to thus permitting the onset of sleep and PS with muscle atonia.

Neural control of heart rate: the role of neuronal networking.

PubMed

Kember, G; Armour, J A; Zamir, M

2011-05-21

Neural control of heart rate, particularly its sympathetic component, is generally thought to reside primarily in the central nervous system, though accumulating evidence suggests that intrathoracic extracardiac and intrinsic cardiac ganglia are also involved. We propose an integrated model in which the control of heart rate is achieved via three neuronal "levels" representing three control centers instead of the conventional one. Most importantly, in this model control is effected through networking between neuronal populations within and among these layers. The results obtained indicate that networking serves to process demands for systemic blood flow before transducing them to cardiac motor neurons. This provides the heart with a measure of protection against the possibility of "overdrive" implied by the currently held centrally driven system. The results also show that localized networking instabilities can lead to sporadic low frequency oscillations that have the characteristics of the well-known Mayer waves. The sporadic nature of Mayer waves has been unexplained so far and is of particular interest in clinical diagnosis. Copyright © 2011 Elsevier Ltd. All rights reserved.

Hunger neurons drive feeding through a sustained, positive reinforcement signal

PubMed Central

Chen, Yiming; Lin, Yen-Chu; Zimmerman, Christopher A; Essner, Rachel A; Knight, Zachary A

2016-01-01

The neural mechanisms underlying hunger are poorly understood. AgRP neurons are activated by energy deficit and promote voracious food consumption, suggesting these cells may supply the fundamental hunger drive that motivates feeding. However recent in vivo recording experiments revealed that AgRP neurons are inhibited within seconds by the sensory detection of food, raising the question of how these cells can promote feeding at all. Here we resolve this paradox by showing that brief optogenetic stimulation of AgRP neurons before food availability promotes intense appetitive and consummatory behaviors that persist for tens of minutes in the absence of continued AgRP neuron activation. We show that these sustained behavioral responses are mediated by a long-lasting potentiation of the rewarding properties of food and that AgRP neuron activity is positively reinforcing. These findings reveal that hunger neurons drive feeding by transmitting a positive valence signal that triggers a stable transition between behavioral states. DOI: http://dx.doi.org/10.7554/eLife.18640.001 PMID:27554486

Galileo's Paradox

NASA Astrophysics Data System (ADS)

Greenslade, Thomas B.

2008-05-01

The paradox is a wonderful teaching tool. The sleepy student in the back row is surprised and wakes up, and the student with the instantly memorized answer is forced into the analytical mode. The diagram in Fig. 1 has the following paradox: A body sliding freely down a chord from the edge of the circle reaches the lowest point on the circle at the same time as a body released simultaneously from the top. This result was first mentioned in a 1602 letter from Galileo Galilei to Guidobaldo dal Monte.

Monosodium glutamate-sensitive hypothalamic neurons contribute to the control of bone mass

NASA Technical Reports Server (NTRS)

Elefteriou, Florent; Takeda, Shu; Liu, Xiuyun; Armstrong, Dawna; Karsenty, Gerard

2003-01-01

Using chemical lesioning we previously identified hypothalamic neurons that are required for leptin antiosteogenic function. In the course of these studies we observed that destruction of neurons sensitive to monosodium glutamate (MSG) in arcuate nuclei did not affect bone mass. However MSG treatment leads to hypogonadism, a condition inducing bone loss. Therefore the normal bone mass of MSG-treated mice suggested that MSG-sensitive neurons may be implicated in the control of bone mass. To test this hypothesis we assessed bone resorption and bone formation parameters in MSG-treated mice. We show here that MSG-treated mice display the expected increase in bone resorption and that their normal bone mass is due to a concomitant increase in bone formation. Correction of MSG-induced hypogonadism by physiological doses of estradiol corrected the abnormal bone resorptive activity in MSG-treated mice and uncovered their high bone mass phenotype. Because neuropeptide Y (NPY) is highly expressed in MSG-sensitive neurons we tested whether NPY regulates bone formation. Surprisingly, NPY-deficient mice had a normal bone mass. This study reveals that distinct populations of hypothalamic neurons are involved in the control of bone mass and demonstrates that MSG-sensitive neurons control bone formation in a leptin-independent manner. It also indicates that NPY deficiency does not affect bone mass.

The Paradoxical Role of Perceived Control in Late Life Health Behavior

PubMed Central

Chipperfield, Judith G.; Perry, Raymond P.; Pekrun, Reinhard; Barchfeld, Petra; Lang, Frieder R.; Hamm, Jeremy M.

2016-01-01

Research has established the health benefits of psychological factors, including the way individuals appraise outcomes. Although many studies confirm that appraising outcomes as controllable is adaptive for health, a paradoxical possibility is largely ignored: Perceived control may be detrimental under some conditions. Our premise was that appraising health as controllable but at the same time ascribing little value to it might signal a dysfunctional psychological mindset that fosters a mistaken sense of invincibility. During face-to-face interviews with a representative sample of older adults (age range = 72–99), we identified individuals with such a potentially maladaptive “invincible” mindset (high perceived control and low health value) and compared them to their counterparts on several outcomes. The findings were consistent with our hypotheses. The invincibles denied future risks, they lacked the activating emotion of fear, and they visited their physicians less often over a subsequent five-year period. Moreover, in contrast to their counterparts, the invincibles did not appear strategic in their approach to seeking care: Even poor health did not prompt them to seek the counsel of a physician. The recognition that psychological appraisals are modifiable highlights the promise of remedial methods to alter maladaptive mindsets, potentially improving quality of life. PMID:26974153

Diode probes for spatiotemporal optical control of multiple neurons in freely moving animals

PubMed Central

Koos, Tibor; Buzsáki, György

2012-01-01

Neuronal control with high temporal precision is possible with optogenetics, yet currently available methods do not enable to control independently multiple locations in the brains of freely moving animals. Here, we describe a diode-probe system that allows real-time and location-specific control of neuronal activity at multiple sites. Manipulation of neuronal activity in arbitrary spatiotemporal patterns is achieved by means of an optoelectronic array, manufactured by attaching multiple diode-fiber assemblies to high-density silicon probes or wire tetrodes and implanted into the brains of animals that are expressing light-responsive opsins. Each diode can be controlled separately, allowing localized light stimulation of neuronal activators and silencers in any temporal configuration and concurrent recording of the stimulated neurons. Because the only connections to the animals are via a highly flexible wire cable, unimpeded behavior is allowed for circuit monitoring and multisite perturbations in the intact brain. The capacity of the system to generate unique neural activity patterns facilitates multisite manipulation of neural circuits in a closed-loop manner and opens the door to addressing novel questions. PMID:22496529

Leptin action through hypothalamic nitric oxide synthase-1-expressing neurons controls energy balance.

PubMed

Leshan, Rebecca L; Greenwald-Yarnell, Megan; Patterson, Christa M; Gonzalez, Ian E; Myers, Martin G

2012-05-01

Few effective measures exist to combat the worldwide obesity epidemic(1), and the identification of potential therapeutic targets requires a deeper understanding of the mechanisms that control energy balance. Leptin, an adipocyte-derived hormone that signals the long-term status of bodily energy stores, acts through multiple types of leptin receptor long isoform (LepRb)-expressing neurons (called here LepRb neurons) in the brain to control feeding, energy expenditure and endocrine function(2-4). The modest contributions to energy balance that are attributable to leptin action in many LepRb populations(5-9) suggest that other previously unidentified hypothalamic LepRb neurons have key roles in energy balance. Here we examine the role of LepRb in neuronal nitric oxide synthase (NOS1)-expressing LebRb (LepRb(NOS1)) neurons that comprise approximately 20% of the total hypothalamic LepRb neurons. Nos1(cre)-mediated genetic ablation of LepRb (Lepr(Nos1KO)) in mice produces hyperphagic obesity, decreased energy expenditure and hyperglycemia approaching that seen in whole-body LepRb-null mice. In contrast, the endocrine functions in Lepr(Nos1KO) mice are only modestly affected by the genetic ablation of LepRb in these neurons. Thus, hypothalamic LepRb(NOS1) neurons are a key site of action of the leptin-mediated control of systemic energy balance.

Hormesis and Paradoxical Effects of Drooping Birch (Betula pendula Roth) Parameters Under Motor Traffic Pollution

PubMed Central

2015-01-01

Various plant indexes are used or recommended for bioindication. However, the nonmonotonic dose–response dependences (hormesis and paradoxical effects) of these indexes are insufficiently explored upon exposure to pollution. We studied the dependences of these Betula pendula indexes on the intensity of motor traffic pollution. Regression analysis did not reveal any dependence of chlorophyll and carotenoid content on traffic intensity (in 2008 and 2010-2013). Lipid peroxidation rate had different versions of paradoxical effects in 2008 and 2010 to 2012 and increased in comparison with control under an increase in pollution level in 2013. In 2010 to 2012, all dose–response dependences for total protein and thiol group content were biphasic and multiphasic paradoxical effects. In 2013, an increase in traffic intensity induced a linear reduction in protein content and an increase in thiol group level in comparison with the control. In most cases, the studied phenological indexes and seed production decreased monotonically in comparison with the control following an increase in traffic intensity. Only in 2010 and 2013, share of fallen leaves had hormesis and paradoxical effect accordingly. Fluctuating asymmetry had a paradoxical effect and hormesis in 2008 and 2012, accordingly, and increased in comparison with the control under an increase in the level of pollution in 2010 to 2011. PMID:26676071

Black Hole Paradoxes

NASA Astrophysics Data System (ADS)

Joshi, Pankaj S.; Narayan, Ramesh

2016-10-01

We propose here that the well-known black hole paradoxes such as the information loss and teleological nature of the event horizon are restricted to a particular idealized case, which is the homogeneous dust collapse model. In this case, the event horizon, which defines the boundary of the black hole, forms initially, and the singularity in the interior of the black hole at a later time. We show that, in contrast, gravitational collapse from physically more realistic initial conditions typically leads to the scenario in which the event horizon and space-time singularity form simultaneously. We point out that this apparently simple modification can mitigate the causality and teleological paradoxes, and also lends support to two recently suggested solutions to the information paradox, namely, the ‘firewall’ and ‘classical chaos’ proposals.

Control of abdominal muscles by brain stem respiratory neurons in the cat

NASA Technical Reports Server (NTRS)

Miller, Alan D.; Ezure, Kazuhisa; Suzuki, Ichiro

1985-01-01

The nature of the control of abdominal muscles by the brain stem respiratory neurons was investigated in decerebrate unanesthetized cats. First, it was determined which of the brain stem respiratory neurons project to the lumbar cord (from which the abdominal muscles receive part of their innervation), by stimulating the neurons monopolarly. In a second part of the study, it was determined if lumbar-projecting respiratory neurons make monosynaptic connections with abdominal motoneurons; in these experiments, discriminate spontaneous spikes of antidromically acivated expiratory (E) neurons were used to trigger activity from both L1 and L2 nerves. A large projection was observed from E neurons in the caudal ventral respiratory group to the contralateral upper lumber cord. However, cross-correlation experiments found only two (out of 47 neuron pairs tested) strong monosynaptic connections between brain stem neurons and abdominal motoneurons.

Fragile X Mental Retardation Protein (FMRP) controls diacylglycerol kinase activity in neurons.

PubMed

Tabet, Ricardos; Moutin, Enora; Becker, Jérôme A J; Heintz, Dimitri; Fouillen, Laetitia; Flatter, Eric; Krężel, Wojciech; Alunni, Violaine; Koebel, Pascale; Dembélé, Doulaye; Tassone, Flora; Bardoni, Barbara; Mandel, Jean-Louis; Vitale, Nicolas; Muller, Dominique; Le Merrer, Julie; Moine, Hervé

2016-06-28

Fragile X syndrome (FXS) is caused by the absence of the Fragile X Mental Retardation Protein (FMRP) in neurons. In the mouse, the lack of FMRP is associated with an excessive translation of hundreds of neuronal proteins, notably including postsynaptic proteins. This local protein synthesis deregulation is proposed to underlie the observed defects of glutamatergic synapse maturation and function and to affect preferentially the hundreds of mRNA species that were reported to bind to FMRP. How FMRP impacts synaptic protein translation and which mRNAs are most important for the pathology remain unclear. Here we show by cross-linking immunoprecipitation in cortical neurons that FMRP is mostly associated with one unique mRNA: diacylglycerol kinase kappa (Dgkκ), a master regulator that controls the switch between diacylglycerol and phosphatidic acid signaling pathways. The absence of FMRP in neurons abolishes group 1 metabotropic glutamate receptor-dependent DGK activity combined with a loss of Dgkκ expression. The reduction of Dgkκ in neurons is sufficient to cause dendritic spine abnormalities, synaptic plasticity alterations, and behavior disorders similar to those observed in the FXS mouse model. Overexpression of Dgkκ in neurons is able to rescue the dendritic spine defects of the Fragile X Mental Retardation 1 gene KO neurons. Together, these data suggest that Dgkκ deregulation contributes to FXS pathology and support a model where FMRP, by controlling the translation of Dgkκ, indirectly controls synaptic proteins translation and membrane properties by impacting lipid signaling in dendritic spine.

Metabolic sensing neurons and the control of energy homeostasis.

PubMed

Levin, Barry E

2006-11-30

The brain and periphery carry on a constant conversation; the periphery informs the brain about its metabolic needs and the brain provides for these needs through its control of somatomotor, autonomic and neurohumoral pathways involved in energy intake, expenditure and storage. Metabolic sensing neurons are the integrators of a variety of metabolic, humoral and neural inputs from the periphery. Such neurons, originally called "glucosensing", also respond to fatty acids, hormones and metabolites from the periphery. They are integrated within neural pathways involved in the regulation of energy homeostasis. Unlike most neurons, they utilize glucose and other metabolites as signaling molecules to regulate their membrane potential and firing rate. For glucosensing neurons, glucokinase acts as the rate-limiting step in glucosensing while the pathways that mediate responses to metabolites like lactate, ketone bodies and fatty acids are less well characterized. Many metabolic sensing neurons also respond to insulin and leptin and other peripheral hormones and receive neural inputs from peripheral organs. Each set of afferent signals arrives with different temporal profiles and by different routes and these inputs are summated at the level of the membrane potential to produce a given neural firing pattern. In some obese individuals, the relative sensitivity of metabolic sensing neurons to various peripheral inputs is genetically reduced. This may provide one mechanism underlying their propensity to become obese when exposed to diets high in fat and caloric density. Thus, metabolic sensing neurons may provide a potential therapeutic target for the treatment of obesity.

Paradoxical aortic stenosis: A systematic review.

PubMed

Cavaca, Rita; Teixeira, Rogério; Vieira, Maria João; Gonçalves, Lino

2017-04-01

Aortic stenosis (AS) is a complex systemic valvular and vascular disease with a high prevalence in developed countries. The new entity "paradoxical low-flow, low-gradient aortic stenosis" refers to cases in which patients have severe AS based on assessment of aortic valve area (AVA) (≤1 cm 2 ) or indexed AVA (≤0.6 cm 2 /m 2 ), but paradoxically have a low mean transvalvular gradient (<40 mmHg) and a low stroke volume index (≤35 ml/m 2 ), despite preserved left ventricular ejection fraction (≥50%). A search was carried out in the PubMed database on paradoxical AS for the period 2007-2014. A total of 57 articles were included for this review. The prevalence of paradoxical AS ranged from 3% to 35% of the population with severe degenerative AS. It was more frequent in females and in older patients. Paradoxical AS was associated with characteristic left ventricular remodeling as well as an increase in systemic arterial stiffness. It was noted that there may be errors and inaccuracies in the calculation of AVA by the continuity equation, which could erroneously suggest the paradoxical phenotype. There are new diagnostic methods to facilitate the study of AS, such as aortic valve calcium score, valvuloarterial impedance and the longitudinal mechanics of the left ventricle. With regard to its natural history, it is not clear whether paradoxical AS corresponds to an advance stage of the disease or if paradoxical AS patients have a distinct phenotype with specific characteristics. Valve replacement, either surgical or percutaneous, may be indicated in patients with severe and symptomatic paradoxical AS. Copyright © 2016 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

Explaining the harmonic sequence paradox.

PubMed

Schmidt, Ulrich; Zimper, Alexander

2012-05-01

According to the harmonic sequence paradox, an expected utility decision maker's willingness to pay for a gamble whose expected payoffs evolve according to the harmonic series is finite if and only if his marginal utility of additional income becomes zero for rather low payoff levels. Since the assumption of zero marginal utility is implausible for finite payoff levels, expected utility theory - as well as its standard generalizations such as cumulative prospect theory - are apparently unable to explain a finite willingness to pay. This paper presents first an experimental study of the harmonic sequence paradox. Additionally, it demonstrates that the theoretical argument of the harmonic sequence paradox only applies to time-patient decision makers, whereas the paradox is easily avoided if time-impatience is introduced. ©2011 The British Psychological Society.

The core paradox.

NASA Technical Reports Server (NTRS)

Kennedy, G. C.; Higgins, G. H.

1973-01-01

Rebuttal of suggestions from various critics attempting to provide an escape from the seeming paradox originated by Higgins and Kennedy's (1971) proposed possibility that the liquid in the outer core was thermally stably stratified and that this stratification might prove a powerful inhibitor to circulation of the outer core fluid of the kind postulated for the generation of the earth's magnetic field. These suggestions are examined and shown to provide no reasonable escape from the core paradox.

Adaptive Fractional-order Control for Synchronization of Two Coupled Neurons in the External Electrical Stimulation

PubMed Central

Mehdiabadi, M. R. Rahmani; Rouhani, E.; Mashhadi, S. K. Mousavi; Jalali, A. A.

2014-01-01

This paper addresses synchronizing two coupled chaotic FitzHugh–Nagumo (FHN) neurons with weakly gap junction under external electrical stimulation (EES). To transmit information among coupled neurons, by generalization of the integer-order FHN equations of the coupled system into the fractional-order in frequency domain using Crone approach, the behavior of each coupled neuron relies on its past behavior and the memorized system can be a better fit for the neuron response. An adaptive fractional-order controller based on the Lyaponuv stability theory was designed to synchronize two neurons electrically coupled with gap junction in EES. The proposed controller is also robust to the inevitable random noise such as disturbances of ionic channels. The simulation results demonstrate the effectiveness of the control scheme. PMID:25337373

Control of proliferation rate of N27 dopaminergic neurons using Transcranial Magnetic Stimulation orientation

NASA Astrophysics Data System (ADS)

Meng, Yiwen; Hadimani, Ravi; Anantharam, Vellareddy; Kanthasamy, Anumantha; Jiles, David

2015-03-01

Transcranial magnetic stimulation (TMS) has been used to investigate possible treatments for a variety of neurological disorders. However, the effect that magnetic fields have on neurons has not been well documented in the literature. We have investigated the effect of different orientation of magnetic field generated by TMS coils with a monophasic stimulator on the proliferation rate of N27 neuronal cells cultured in flasks and multi-well plates. The proliferation rate of neurons would increase by exposed horizontally adherent N27 cells to a magnetic field pointing upward through the neuronal proliferation layer compared with the control group. On the other hand, proliferation rate would decrease in cells exposed to a magnetic field pointing downward through the neuronal growth layer compared with the control group. We confirmed results obtained from the Trypan-blue and automatic cell counting methods with those from the CyQuant and MTS cell viability assays. Our findings could have important implications for the preclinical development of TMS treatments of neurological disorders and represents a new method to control the proliferation rate of neuronal cells.

From the BMI paradox to the obesity paradox: the obesity-mortality association in coronary heart disease.

PubMed

Antonopoulos, A S; Oikonomou, E K; Antoniades, C; Tousoulis, D

2016-10-01

Despite a strong association between body weight and mortality in the general population, clinical evidence suggests better clinical outcome of overweight or obese individuals with established coronary heart disease. This finding has been termed the 'obesity paradox', but its existence remains a point of debate, because it is mostly observed when body mass index (BMI) is used to define obesity. Inherent limitations of BMI as an index of adiposity, as well as methodological biases and the presence of confounding factors, may account for the observed findings of clinical studies. In this review, our aim is to present the data that support the presence of a BMI paradox in coronary heart disease and then explore whether next to a BMI paradox a true obesity paradox exists as well. We conclude by attempting to link the obesity paradox notion to available translational research data supporting a 'healthy', protective adipose tissue phenotype. © 2016 World Obesity. © 2016 World Obesity.

Tracing neuronal circuits in transgenic animals by transneuronal control of transcription (TRACT)

PubMed Central

Huang, Ting-hao; Niesman, Peter; Arasu, Deepshika; Lee, Donghyung; De La Cruz, Aubrie L; Callejas, Antuca; Hong, Elizabeth J

2017-01-01

Understanding the computations that take place in brain circuits requires identifying how neurons in those circuits are connected to one another. We describe a technique called TRACT (TRAnsneuronal Control of Transcription) based on ligand-induced intramembrane proteolysis to reveal monosynaptic connections arising from genetically labeled neurons of interest. In this strategy, neurons expressing an artificial ligand (‘donor’ neurons) bind to and activate a genetically-engineered artificial receptor on their synaptic partners (‘receiver’ neurons). Upon ligand-receptor binding at synapses the receptor is cleaved in its transmembrane domain and releases a protein fragment that activates transcription in the synaptic partners. Using TRACT in Drosophila we have confirmed the connectivity between olfactory receptor neurons and their postsynaptic targets, and have discovered potential new connections between neurons in the circadian circuit. Our results demonstrate that the TRACT method can be used to investigate the connectivity of neuronal circuits in the brain. PMID:29231171

Frequencies of neuronal autoantibodies in healthy controls

PubMed Central

Lang, Katharina

2017-01-01

Objective: To provide an extensive overview on the prevalence of antibodies against neuronal surfaces (neuronal surface antibody [NSAb]) in healthy participants and disease controls. Methods: We searched the PubMed database (1974 to October 2016) for studies that analyzed frequencies of 22 different NSAbs in serum or CSF and included controls. Antibody prevalence was calculated for patients with NSAb-mediated disease and controls, including healthy participants, and those with neurologic and nonneurologic diseases. Different assays for antibody detection were compared. Results: In 309 articles, 743,299 antibody tests for 22 NSAbs were performed, including 30,485 tests for 19 NSAbs in healthy controls (HCs). Of these, 26,423 (86.7%) were tested with current standard methods, usually cell-based assays. Prevalence was very low in HCs (mean 0.23%, absent for 9/19 antibodies), and test numbers ranged from 21 to 3,065 per antibody. One study reported >1,000 healthy participants, and the others contained 21–274 samples. CSF samples were virtually not available from HCs. NSAb prevalence was considerably higher (1.5%) in 69,850 disease controls, i.e., patients not initially suspected to have NSAb-mediated diseases. Antibody determination in controls using nonstandard assays (such as ELISA) resulted in 6% positivity. Conclusions: NSAbs are rarely found in healthy participants, particularly with standard detection methods, suggesting high disease specificity and supporting their diagnostic usefulness. Conversely, positive titers in atypical patients might point to the still expanding phenotypic spectrum. Future studies should include more CSF samples, data from HCs, and experimental evidence for antibody pathogenicity. PMID:28761905

Obesity-driven synaptic remodeling affects endocannabinoid control of orexinergic neurons

PubMed Central

Cristino, Luigia; Busetto, Giuseppe; Imperatore, Roberta; Ferrandino, Ida; Palomba, Letizia; Silvestri, Cristoforo; Petrosino, Stefania; Orlando, Pierangelo; Bentivoglio, Marina; Mackie, Kenneth; Di Marzo, Vincenzo

2013-01-01

Acute or chronic alterations in energy status alter the balance between excitatory and inhibitory synaptic transmission and associated synaptic plasticity to allow for the adaptation of energy metabolism to new homeostatic requirements. The impact of such changes on endocannabinoid and cannabinoid receptor type 1 (CB1)-mediated modulation of synaptic transmission and strength is not known, despite the fact that this signaling system is an important target for the development of new drugs against obesity. We investigated whether CB1-expressing excitatory vs. inhibitory inputs to orexin-A–containing neurons in the lateral hypothalamus are altered in obesity and how this modifies endocannabinoid control of these neurons. In lean mice, these inputs are mostly excitatory. By confocal and ultrastructural microscopic analyses, we observed that in leptin-knockout (ob/ob) obese mice, and in mice with diet-induced obesity, orexinergic neurons receive predominantly inhibitory CB1-expressing inputs and overexpress the biosynthetic enzyme for the endocannabinoid 2-arachidonoylglycerol, which retrogradely inhibits synaptic transmission at CB1-expressing axon terminals. Patch-clamp recordings also showed increased CB1-sensitive inhibitory innervation of orexinergic neurons in ob/ob mice. These alterations are reversed by leptin administration, partly through activation of the mammalian target of rapamycin pathway in neuropeptide-Y-ergic neurons of the arcuate nucleus, and are accompanied by CB1-mediated enhancement of orexinergic innervation of target brain areas. We propose that enhanced inhibitory control of orexin-A neurons, and their CB1-mediated disinhibition, are a consequence of leptin signaling impairment in the arcuate nucleus. We also provide initial evidence of the participation of this phenomenon in hyperphagia and hormonal dysregulation in obesity. PMID:23630288

Leptin receptor expression in hindbrain Glp-1 neurons regulates food intake and energy balance in mice.

PubMed

Scott, Michael M; Williams, Kevin W; Rossi, Jari; Lee, Charlotte E; Elmquist, Joel K

2011-06-01

Leptin is an adipose-derived hormone that signals to inform the brain of nutrient status; loss of leptin signaling results in marked hyperphagia and obesity. Recent work has identified several groups of neurons that contribute to the effects of leptin to regulate energy balance, but leptin receptors are distributed throughout the brain, and the function of leptin signaling in discrete neuronal populations outside of the hypothalamus has not been defined. In the current study, we produced mice in which the long form of the leptin receptor (Lepr) was selectively ablated using Cre-recombinase selectively expressed in the hindbrain under control of the paired-like homeobox 2b (Phox2b) promoter (Phox2b Cre Lepr(flox/flox) mice). In these mice, Lepr was deleted from glucagon-like 1 peptide-expressing neurons resident in the nucleus of the solitary tract. Phox2b Cre Lepr(flox/flox) mice were hyperphagic, displayed increased food intake after fasting, and gained weight at a faster rate than wild-type controls. Paradoxically, Phox2b Cre Lepr(flox/flox) mice also exhibited an increased metabolic rate independent of a change in locomotor activity that was dependent on food intake, and glucose homeostasis was normal. Together, these data support a physiologically important role of direct leptin action in the hindbrain.

Paradoxical anaerobism in desert pupfish.

PubMed

Heuton, Matt; Ayala, Luis; Burg, Chris; Dayton, Kyle; McKenna, Ken; Morante, Aldo; Puentedura, Georgina; Urbina, Natasha; Hillyard, Stanley; Steinberg, Spencer; van Breukelen, Frank

2015-12-01

In order to estimate metabolic demands of desert pupfish for conservation purposes, we measured oxygen consumption in fish acclimated to the ecologically relevant temperatures of 28 or 33°C. For these experiments, we used fish derived from a refuge population of Devils Hole pupfish (Cyprinodon diabolis). Measurement of routine oxygen consumption (V̇O2,routine) revealed some 33°C-acclimated fish (10% of 295 assayed fish) periodically exhibited periods of no measurable oxygen consumption despite available ambient oxygen tensions that were above the critical PO2. We call this phenomenon paradoxical anaerobism. The longest observed continuous bout with no oxygen consumption was 149 min, although typical bouts were much shorter. Fish maintained normal posture and ventilation rate (>230 ventilations per minute) during paradoxical anaerobism. Fish rarely demonstrated a compensatory increase in oxygen use following a period of paradoxical anaerobism. In contrast, only one out of 262 sampled fish acclimated at 28°C spontaneously demonstrated paradoxical anaerobism. Muscle lactate concentration was not elevated during periods of paradoxical anaerobism. However, the amount of ethanol released by the 33°C-acclimated fish was 7.3 times greater than that released by the 28°C acclimation group, suggesting ethanol may be used as an alternative end product of anaerobic metabolism. Exposure to exogenous ethanol, in concentrations as low as 0.1%, produced periods of paradoxical anaerobism even in 28°C-acclimated fish. © 2015. Published by The Company of Biologists Ltd.

Glucose-responsive neurons of the paraventricular thalamus control sucrose-seeking behavior.

PubMed

Labouèbe, Gwenaël; Boutrel, Benjamin; Tarussio, David; Thorens, Bernard

2016-08-01

Feeding behavior is governed by homeostatic needs and motivational drive to obtain palatable foods. Here, we identify a population of glutamatergic neurons in the paraventricular thalamus of mice that express the glucose transporter Glut2 (encoded by Slc2a2) and project to the nucleus accumbens. These neurons are activated by hypoglycemia and, in freely moving mice, their activation by optogenetics or Slc2a2 inactivation increases motivated sucrose-seeking but not saccharin-seeking behavior. These neurons may control sugar overconsumption in obesity and diabetes.

Weighing the Evidence in Peters' Rule: Does Neuronal Morphology Predict Connectivity?

PubMed

Rees, Christopher L; Moradi, Keivan; Ascoli, Giorgio A

2017-02-01

Although the importance of network connectivity is increasingly recognized, identifying synapses remains challenging relative to the routine characterization of neuronal morphology. Thus, researchers frequently employ axon-dendrite colocations as proxies of potential connections. This putative equivalence, commonly referred to as Peters' rule, has been recently studied at multiple levels and scales, fueling passionate debates regarding its validity. Our critical literature review identifies three conceptually distinct but often confused applications: inferring neuron type circuitry, predicting synaptic contacts among individual cells, and estimating synapse numbers within neuron pairs. Paradoxically, at the originally proposed cell-type level, Peters' rule remains largely untested. Leveraging Hippocampome.org, we validate and refine the relationship between axonal-dendritic colocations and synaptic circuits, clarifying the interpretation of existing and forthcoming data. Copyright © 2016 Elsevier Ltd. All rights reserved.

Independent controls for neocortical neuron production and histogenetic cell death

NASA Technical Reports Server (NTRS)

Verney, C.; Takahashi, T.; Bhide, P. G.; Nowakowski, R. S.; Caviness, V. S. Jr

2000-01-01

We estimated the proportion of cells eliminated by histogenetic cell death during the first 2 postnatal weeks in areas 1, 3 and 40 of the mouse parietal neocortex. For each layer and for the subcortical white matter in each neocortical area, the number of dying cells per mm(2) was calculated and the proportionate cell death for each day of the 2-week interval was estimated. The data show that cell death proceeds essentially uniformly across the neocortical areas and layers and that it does not follow either the spatiotemporal gradient of cell cycle progression in the pseudostratified ventricular epithelium of the cerebral wall, the source of neocortical neurons, or the 'inside-out' neocortical neuronogenetic sequence. Therefore, we infer that the control mechanisms of neocortical histogenetic cell death are independent of mechanisms controlling neuronogenesis or neuronal migration but may be associated with the ingrowth, expansion and a system-wide matching of neuronal connectivity. Copyright 2000 S. Karger AG, Basel.

Middle ground approach to paradox: Within- and between-culture examination of the creative benefits of paradoxical frames.

PubMed

Leung, Angela K-Y; Liou, Shyhnan; Miron-Spektor, Ella; Koh, Brandon; Chan, David; Eisenberg, Roni; Schneider, Iris

2018-03-01

Thriving in increasingly complex and ambiguous environments requires creativity and the capability to reconcile conflicting demands. Recent evidence with Western samples has suggested that paradoxical frames, or mental templates that encourage individuals to recognize and embrace contradictions, could produce creative benefits. We extended the timely, but understudied, topic by studying the nuances of for whom and why creative advantages of paradoxical frames emerge. We suggest that people endorsing a middle ground approach are less likely to scrutinize conflict and reconcile with integrative solutions, thus receiving less creative benefits of paradoxical frames. Five studies that examined individual and cultural differences in middle ground endorsement support our theory. Study 1 found that paradoxical frames increased creativity, but failed to replicate that experienced conflict mediated the relationship in a Taiwanese sample. In both within- and between-culture analysis, we showed that the creative advantages of thinking paradoxically and experiencing conflict emerged among individuals who endorse lower (vs. higher) levels of middle ground (Study 2) and among Israelis whose culture predominantly endorses middle ground strategy less, but not among Singaporeans whose culture predominantly endorses middle ground more (Study 3). Study 4 further demonstrated the causal role of middle ground in the paradox-conflict-creativity link. To answer "why," Study 5 situationally induced integrative complex thinking that sets distinctions and forms syntheses among contradictory elements, and found that low endorsers of middle ground performed more creatively when they engaged integrative complex thinking to cope with paradoxes. This program of studies offers important insights on harnessing paradoxical experiences to catalyze creativity. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Spinal Projection Neurons Control Turning Behaviors in Zebrafish

PubMed Central

Huang, Kuo-Hua; Ahrens, Misha B.; Dunn, Timothy W.; Engert, Florian

2013-01-01

Summary Discrete populations of brainstem spinal projection neurons (SPNs) have been shown to exhibit behavior-specific responses during locomotion [1–9], suggesting that separate descending pathways, each dedicated to a specific behavior, control locomotion. In an alternative model, a large variety of motor outputs could be generated from different combinations of a small number of basic motor pathways. We examined this possibility by studying the precise role of ventromedially located hindbrain SPNs (vSPNs) in generating turning behaviors. We found that unilateral laser ablation of vSPNs reduces the tail deflection and cycle period specifically during the first undulation cycle of a swim bout, whereas later tail movements are unaffected. This holds true during phototaxic [10], optomotor [11], dark-flash-induced [12], and spontaneous turns [13], suggesting a universal role of these neurons in controlling turning behaviors. Importantly, we found that the ablation not only abolishes turns but also results in a dramatic increase in the number of forward swims, suggesting that these neurons transform forward swims into turns by introducing turning kinematics into a basic motor pattern of symmetric tail undulations. Finally, we show that vSPN activity is direction specific and graded by turning angle. Together, these results provide a clear example of how a specific motor pattern can be transformed into different behavioral events by the graded activation of a small set of SPNs. PMID:23910662

Area-specific temporal control of corticospinal motor neuron differentiation by COUP-TFI

PubMed Central

Tomassy, Giulio Srubek; De Leonibus, Elvira; Jabaudon, Denis; Lodato, Simona; Alfano, Christian; Mele, Andrea; Macklis, Jeffrey D.; Studer, Michèle

2010-01-01

Transcription factors with gradients of expression in neocortical progenitors give rise to distinct motor and sensory cortical areas by controlling the area-specific differentiation of distinct neuronal subtypes. However, the molecular mechanisms underlying this area-restricted control are still unclear. Here, we show that COUP-TFI controls the timing of birth and specification of corticospinal motor neurons (CSMN) in somatosensory cortex via repression of a CSMN differentiation program. Loss of COUP-TFI function causes an area-specific premature generation of neurons with cardinal features of CSMN, which project to subcerebral structures, including the spinal cord. Concurrently, genuine CSMN differentiate imprecisely and do not project beyond the pons, together resulting in impaired skilled motor function in adult mice with cortical COUP-TFI loss-of-function. Our findings indicate that COUP-TFI exerts critical areal and temporal control over the precise differentiation of CSMN during corticogenesis, thereby enabling the area-specific functional features of motor and sensory areas to arise. PMID:20133588

Noise effects on robust synchronization of a small pacemaker neuronal ensemble via nonlinear controller: electronic circuit design.

PubMed

Megam Ngouonkadi, Elie Bertrand; Fotsin, Hilaire Bertrand; Kabong Nono, Martial; Louodop Fotso, Patrick Herve

2016-10-01

In this paper, we report on the synchronization of a pacemaker neuronal ensemble constituted of an AB neuron electrically coupled to two PD neurons. By the virtue of this electrical coupling, they can fire synchronous bursts of action potential. An external master neuron is used to induce to the whole system the desired dynamics, via a nonlinear controller. Such controller is obtained by a combination of sliding mode and feedback control. The proposed controller is able to offset uncertainties in the synchronized systems. We show how noise affects the synchronization of the pacemaker neuronal ensemble, and briefly discuss its potential benefits in our synchronization scheme. An extended Hindmarsh-Rose neuronal model is used to represent a single cell dynamic of the network. Numerical simulations and Pspice implementation of the synchronization scheme are presented. We found that, the proposed controller reduces the stochastic resonance of the network when its gain increases.

Rapid acquisition of novel interface control by small ensembles of arbitrarily selected primary motor cortex neurons

PubMed Central

Law, Andrew J.; Rivlis, Gil

2014-01-01

Pioneering studies demonstrated that novel degrees of freedom could be controlled individually by directly encoding the firing rate of single motor cortex neurons, without regard to each neuron's role in controlling movement of the native limb. In contrast, recent brain-computer interface work has emphasized decoding outputs from large ensembles that include substantially more neurons than the number of degrees of freedom being controlled. To bridge the gap between direct encoding by single neurons and decoding output from large ensembles, we studied monkeys controlling one degree of freedom by comodulating up to four arbitrarily selected motor cortex neurons. Performance typically exceeded random quite early in single sessions and then continued to improve to different degrees in different sessions. We therefore examined factors that might affect performance. Performance improved with larger ensembles. In contrast, other factors that might have reflected preexisting synaptic architecture—such as the similarity of preferred directions—had little if any effect on performance. Patterns of comodulation among ensemble neurons became more consistent across trials as performance improved over single sessions. Compared with the ensemble neurons, other simultaneously recorded neurons showed less modulation. Patterns of voluntarily comodulated firing among small numbers of arbitrarily selected primary motor cortex (M1) neurons thus can be found and improved rapidly, with little constraint based on the normal relationships of the individual neurons to native limb movement. This rapid flexibility in relationships among M1 neurons may in part underlie our ability to learn new movements and improve motor skill. PMID:24920030

Predator interference effects on biological control: The "paradox" of the generalist predator revisited

NASA Astrophysics Data System (ADS)

Parshad, Rana D.; Bhowmick, Suman; Quansah, Emmanuel; Basheer, Aladeen; Upadhyay, Ranjit Kumar

2016-10-01

An interesting conundrum in biological control questions the efficiency of generalist predators as biological control agents. Theory suggests, generalist predators are poor agents for biological control, primarily due to mutual interference. However field evidence shows they are actually quite effective in regulating pest densities. In this work we provide a plausible answer to this paradox. We analyze a three species model, where a generalist top predator is introduced into an ecosystem as a biological control, to check the population of a middle predator, that in turn is depredating on a prey species. We show that the inclusion of predator interference alone, can cause the solution of the top predator equation to blow-up in finite time, while there is global existence in the no interference case. This result shows that interference could actually cause a population explosion of the top predator, enabling it to control the target species, thus corroborating recent field evidence. Our results might also partially explain the population explosion of certain species, introduced originally for biological control purposes, such as the cane toad (Bufo marinus) in Australia, which now functions as a generalist top predator. We also show both Turing instability and spatio-temporal chaos in the model. Lastly we investigate time delay effects.

Cocaine sensitization increases subthreshold activity in dopamine neurons from the ventral tegmental area.

PubMed

Arencibia-Albite, Francisco; Vázquez-Torres, Rafael; Jiménez-Rivera, Carlos A

2017-02-01

The progressive escalation of psychomotor responses that results from repeated cocaine administration is termed sensitization. This phenomenon alters the intrinsic properties of dopamine (DA) neurons from the ventral tegmental area (VTA), leading to enhanced dopaminergic transmission in the mesocorticolimbic network. The mechanisms underlying this augmented excitation are nonetheless poorly understood. DA neurons display the hyperpolarization-activated, nonselective cation current, dubbed I h We recently demonstrated that I h and membrane capacitance are substantially reduced in VTA DA cells from cocaine-sensitized rats. The present study shows that 7 days of cocaine withdrawal did not normalize I h and capacitance. In cells from cocaine-sensitized animals, the amplitude of excitatory synaptic potentials, at -70 mV, was ∼39% larger in contrast to controls. Raise and decay phases of the synaptic signal were faster under cocaine, a result associated with a reduced membrane time constant. Synaptic summation was paradoxically elevated by cocaine exposure, as it consisted of a significantly reduced summation indexed but a considerably increased depolarization. These effects are at least a consequence of the reduced capacitance. I h attenuation is unlikely to explain such observations, since at -70 mV, no statistical differences exist in I h or input resistance. The neuronal shrinkage associated with a diminished capacitance may help to understand two fundamental elements of drug addiction: incentive sensitization and negative emotional states. A reduced cell size may lead to substantial enhancement of cue-triggered bursting, which underlies drug craving and reward anticipation, whereas it could also result in DA depletion, as smaller neurons might express low levels of tyrosine hydroxylase. This work uses a new approach that directly extracts important biophysical parameters from alpha function-evoked synaptic potentials. Two of these parameters are the cell membrane

The MedDRA paradox.

PubMed

Merrill, Gary H

2008-11-06

MedDRA (the Medical Dictionary for Regulatory Activities Terminology) is a controlled vocabulary widely used as a medical coding scheme. However, MedDRA's characterization of its structural hierarchy exhibits some confusing and paradoxical features. The goal of this paper is to examine these features, determine whether there is a coherent view of the MedDRA hierarchy that emerges, and explore what lessons are to be learned from this for using MedDRA and similar terminologies in a broad medical informatics context that includes relations among multiple disparate terminologies, thesauri, and ontologies.

Striatopallidal neurons control avoidance behavior in exploratory tasks.

PubMed

LeBlanc, Kimberly H; London, Tanisha D; Szczot, Ilona; Bocarsly, Miriam E; Friend, Danielle M; Nguyen, Katrina P; Mengesha, Marda M; Rubinstein, Marcelo; Alvarez, Veronica A; Kravitz, Alexxai V

2018-04-25

The dorsal striatum has been linked to decision-making under conflict, but the mechanism by which striatal neurons contribute to approach-avoidance conflicts remains unclear. We hypothesized that striatopallidal dopamine D2 receptor (D2R)-expressing neurons promote avoidance, and tested this hypothesis in two exploratory approach-avoidance conflict paradigms in mice: the elevated zero maze and open field. Genetic elimination of D2Rs on striatopallidal neurons (iMSNs), but not other neural populations, increased avoidance of the open areas in both tasks, in a manner that was dissociable from global changes in movement. Population calcium activity of dorsomedial iMSNs was disrupted in mice lacking D2Rs on iMSNs, suggesting that disrupted output of iMSNs contributes to heightened avoidance behavior. Consistently, artificial disruption of iMSN output with optogenetic stimulation heightened avoidance of open areas of these tasks, while inhibition of iMSN output reduced avoidance. We conclude that dorsomedial striatal iMSNs control approach-avoidance conflicts in exploratory tasks, and highlight this neural population as a potential target for reducing avoidance in anxiety disorders.

Heavy metals in locus ceruleus and motor neurons in motor neuron disease.

PubMed

Pamphlett, Roger; Kum Jew, Stephen

2013-12-12

The causes of sporadic amyotrophic lateral sclerosis (SALS) and other types of motor neuron disease (MND) remain largely unknown. Heavy metals have long been implicated in MND, and it has recently been shown that inorganic mercury selectively enters human locus ceruleus (LC) and motor neurons. We therefore used silver nitrate autometallography (AMG) to look for AMG-stainable heavy metals (inorganic mercury and bismuth) in LC and motor neurons of 24 patients with MND (18 with SALS and 6 with familial MND) and in the LC of 24 controls. Heavy metals in neurons were found in significantly more MND patients than in controls when comparing: (1) the presence of any versus no heavy metal-containing LC neurons (MND 88%, controls 42%), (2) the median percentage of heavy metal-containing LC neurons (MND 9.5%, control 0.0%), and (3) numbers of individuals with heavy metal-containing LC neurons in the upper half of the percentage range (MND 75%, controls 25%). In MND patients, 67% of remaining spinal motor neurons contained heavy metals; smaller percentages were found in hypoglossal, nucleus ambiguus and oculomotor neurons, but none in cortical motor neurons. The majority of MND patients had heavy metals in both LC and spinal motor neurons. No glia or other neurons, including neuromelanin-containing neurons of the substantia nigra, contained stainable heavy metals. Uptake of heavy metals by LC and lower motor neurons appears to be fairly common in humans, though heavy metal staining in the LC, most likely due to inorganic mercury, was seen significantly more often in MND patients than in controls. The LC innervates many cell types that are affected in MND, and it is possible that MND is triggered by toxicant-induced interactions between LC and motor neurons.

Heavy metals in locus ceruleus and motor neurons in motor neuron disease

PubMed Central

2013-01-01

Background The causes of sporadic amyotrophic lateral sclerosis (SALS) and other types of motor neuron disease (MND) remain largely unknown. Heavy metals have long been implicated in MND, and it has recently been shown that inorganic mercury selectively enters human locus ceruleus (LC) and motor neurons. We therefore used silver nitrate autometallography (AMG) to look for AMG-stainable heavy metals (inorganic mercury and bismuth) in LC and motor neurons of 24 patients with MND (18 with SALS and 6 with familial MND) and in the LC of 24 controls. Results Heavy metals in neurons were found in significantly more MND patients than in controls when comparing: (1) the presence of any versus no heavy metal-containing LC neurons (MND 88%, controls 42%), (2) the median percentage of heavy metal-containing LC neurons (MND 9.5%, control 0.0%), and (3) numbers of individuals with heavy metal-containing LC neurons in the upper half of the percentage range (MND 75%, controls 25%). In MND patients, 67% of remaining spinal motor neurons contained heavy metals; smaller percentages were found in hypoglossal, nucleus ambiguus and oculomotor neurons, but none in cortical motor neurons. The majority of MND patients had heavy metals in both LC and spinal motor neurons. No glia or other neurons, including neuromelanin-containing neurons of the substantia nigra, contained stainable heavy metals. Conclusions Uptake of heavy metals by LC and lower motor neurons appears to be fairly common in humans, though heavy metal staining in the LC, most likely due to inorganic mercury, was seen significantly more often in MND patients than in controls. The LC innervates many cell types that are affected in MND, and it is possible that MND is triggered by toxicant-induced interactions between LC and motor neurons. PMID:24330485

Barn and Pole Paradox: Revisited

ERIC Educational Resources Information Center

Cacioppo, Robert; Gangopadhyaya, Asim

2012-01-01

Paradoxes have played great instructive roles in many cultures. They provide an excellent paradigm for teaching concepts that require deep reflection. In this article, the authors present two different paradoxes related to the length contraction in special relativity and explain their resolution. They hope that these two Gedanken experiments and…

Amyloid precursor protein controls cholesterol turnover needed for neuronal activity

PubMed Central

Pierrot, Nathalie; Tyteca, Donatienne; D'auria, Ludovic; Dewachter, Ilse; Gailly, Philippe; Hendrickx, Aurélie; Tasiaux, Bernadette; Haylani, Laetitia El; Muls, Nathalie; N'Kuli, Francisca; Laquerrière, Annie; Demoulin, Jean-Baptiste; Campion, Dominique; Brion, Jean-Pierre; Courtoy, Pierre J; Kienlen-Campard, Pascal; Octave, Jean-Noël

2013-01-01

Perturbation of lipid metabolism favours progression of Alzheimer disease, in which processing of Amyloid Precursor Protein (APP) has important implications. APP cleavage is tightly regulated by cholesterol and APP fragments regulate lipid homeostasis. Here, we investigated whether up or down regulation of full-length APP expression affected neuronal lipid metabolism. Expression of APP decreased HMG-CoA reductase (HMGCR)-mediated cholesterol biosynthesis and SREBP mRNA levels, while its down regulation had opposite effects. APP and SREBP1 co-immunoprecipitated and co-localized in the Golgi. This interaction prevented Site-2 protease-mediated processing of SREBP1, leading to inhibition of transcription of its target genes. A GXXXG motif in APP sequence was critical for regulation of HMGCR expression. In astrocytes, APP and SREBP1 did not interact nor did APP affect cholesterol biosynthesis. Neuronal expression of APP decreased both HMGCR and cholesterol 24-hydroxylase mRNA levels and consequently cholesterol turnover, leading to inhibition of neuronal activity, which was rescued by geranylgeraniol, generated in the mevalonate pathway, in both APP expressing and mevastatin treated neurons. We conclude that APP controls cholesterol turnover needed for neuronal activity. PMID:23554170

Spinal projection neurons control turning behaviors in zebrafish.

PubMed

Huang, Kuo-Hua; Ahrens, Misha B; Dunn, Timothy W; Engert, Florian

2013-08-19

Discrete populations of brainstem spinal projection neurons (SPNs) have been shown to exhibit behavior-specific responses during locomotion [1-9], suggesting that separate descending pathways, each dedicated to a specific behavior, control locomotion. In an alternative model, a large variety of motor outputs could be generated from different combinations of a small number of basic motor pathways. We examined this possibility by studying the precise role of ventromedially located hindbrain SPNs (vSPNs) in generating turning behaviors. We found that unilateral laser ablation of vSPNs reduces the tail deflection and cycle period specifically during the first undulation cycle of a swim bout, whereas later tail movements are unaffected. This holds true during phototaxic [10], optomotor [11], dark-flash-induced [12], and spontaneous turns [13], suggesting a universal role of these neurons in controlling turning behaviors. Importantly, we found that the ablation not only abolishes turns but also results in a dramatic increase in the number of forward swims, suggesting that these neurons transform forward swims into turns by introducing turning kinematics into a basic motor pattern of symmetric tail undulations. Finally, we show that vSPN activity is direction specific and graded by turning angle. Together, these results provide a clear example of how a specific motor pattern can be transformed into different behavioral events by the graded activation of a small set of SPNs. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Simpson's paradox in psychological science: a practical guide

PubMed Central

Kievit, Rogier A.; Frankenhuis, Willem E.; Waldorp, Lourens J.; Borsboom, Denny

2013-01-01

The direction of an association at the population-level may be reversed within the subgroups comprising that population—a striking observation called Simpson's paradox. When facing this pattern, psychologists often view it as anomalous. Here, we argue that Simpson's paradox is more common than conventionally thought, and typically results in incorrect interpretations—potentially with harmful consequences. We support this claim by reviewing results from cognitive neuroscience, behavior genetics, clinical psychology, personality psychology, educational psychology, intelligence research, and simulation studies. We show that Simpson's paradox is most likely to occur when inferences are drawn across different levels of explanation (e.g., from populations to subgroups, or subgroups to individuals). We propose a set of statistical markers indicative of the paradox, and offer psychometric solutions for dealing with the paradox when encountered—including a toolbox in R for detecting Simpson's paradox. We show that explicit modeling of situations in which the paradox might occur not only prevents incorrect interpretations of data, but also results in a deeper understanding of what data tell us about the world. PMID:23964259

Client cognitive responses to counselor paradoxical and nonparadoxical directives.

PubMed

Lee, D Y; Rossiter, B; Martin, J; Uhlemann, M R

1990-09-01

Client cognitive responses to counselor paradoxical and nonparadoxical directives were examined. It was predicted (a) that clients who received paradoxical symptom prescriptions would display a greater negativity toward the counselor and counseling than those who received nonparadoxical directives; and (b) that clients who received no rationale for the paradoxical directives would display a greater negativity than those who received a rationale. Thirty clients who had reported performance anxiety received one 45-minute counseling interview. Ten clients received paradoxical directives with a rationale, 10 received paradoxical directives with no rationale, and 10 received nonparadoxical directives. Results showed no significant differences in either client in-session negativity or out-of-session implementation of directives between the paradoxical and nonparadoxical conditions and between the rationale and no rationale paradoxical conditions. Possible implications of the findings are discussed.

The Use of Paradoxes as an Instructional Strategy.

ERIC Educational Resources Information Center

Rastovac, John J.; Slavsky, David B.

1986-01-01

Describes a study in which paradoxes about seasons, hemispheres, and altitude were used to teach concepts in climatology. The misconceptions commonly held about the earth-sun distance relationship were used as an instructional strategy with an experimental group, which outgained the control group on an achievement test. (TW)

Hoxa2 and Hoxb2 control dorsoventral patterns of neuronal development in the rostral hindbrain.

PubMed

Davenne, M; Maconochie, M K; Neun, R; Pattyn, A; Chambon, P; Krumlauf, R; Rijli, F M

1999-04-01

Little is known about how the generation of specific neuronal types at stereotypic positions within the hindbrain is linked to Hox gene-mediated patterning. Here, we show that during neurogenesis, Hox paralog group 2 genes control both anteroposterior (A-P) and dorsoventral (D-V) patterning. Hoxa2 and Hoxb2 differentially regulate, in a rhombomere-specific manner, the expression of several genes in broad D-V-restricted domains or narrower longitudinal columns of neuronal progenitors, immature neurons, and differentiating neuronal subtypes. Moreover, Hoxa2 and Hoxb2 can functionally synergize in controlling the development of ventral neuronal subtypes in rhombomere 3 (r3). Thus, in addition to their roles in A-P patterning, Hoxa2 and Hoxb2 have distinct and restricted functions along the D-V axis during neurogenesis, providing insights into how neuronal fates are assigned at stereotypic positions within the hindbrain.

Yule-Simpson's Paradox in Research

ERIC Educational Resources Information Center

Goltz, Heather Honore; Smith, Matthew Lee

2010-01-01

Yule (1903) and Simpson (1951) described a statistical paradox that occurs when data is aggregated. In such situations, aggregated data may reveal a trend that directly contrasts those of sub-groups trends. In fact, the aggregate data trends may even be opposite in direction of sub-group trends. To reveal Yule-Simpson's paradox (YSP)-type…

Enjoying Sad Music: Paradox or Parallel Processes?

PubMed Central

Schubert, Emery

2016-01-01

Enjoyment of negative emotions in music is seen by many as a paradox. This article argues that the paradox exists because it is difficult to view the process that generates enjoyment as being part of the same system that also generates the subjective negative feeling. Compensation theories explain the paradox as the compensation of a negative emotion by the concomitant presence of one or more positive emotions. But compensation brings us no closer to explaining the paradox because it does not explain how experiencing sadness itself is enjoyed. The solution proposed is that an emotion is determined by three critical processes—labeled motivational action tendency (MAT), subjective feeling (SF) and Appraisal. For many emotions the MAT and SF processes are coupled in valence. For example, happiness has positive MAT and positive SF, annoyance has negative MAT and negative SF. However, it is argued that in an aesthetic context, such as listening to music, emotion processes can become decoupled. The decoupling is controlled by the Appraisal process, which can assess if the context of the sadness is real-life (where coupling occurs) or aesthetic (where decoupling can occur). In an aesthetic context sadness retains its negative SF but the aversive, negative MAT is inhibited, leaving sadness to still be experienced as a negative valanced emotion, while contributing to the overall positive MAT. Individual differences, mood and previous experiences mediate the degree to which the aversive aspects of MAT are inhibited according to this Parallel Processing Hypothesis (PPH). The reason for hesitancy in considering or testing PPH, as well as the preponderance of research on sadness at the exclusion of other negative emotions, are discussed. PMID:27445752

Deconstructing the smoking-preeclampsia paradox through a counterfactual framework.

PubMed

Luque-Fernandez, Miguel Angel; Zoega, Helga; Valdimarsdottir, Unnur; Williams, Michelle A

2016-06-01

Although smoking during pregnancy may lead to many adverse outcomes, numerous studies have reported a paradoxical inverse association between maternal cigarette smoking during pregnancy and preeclampsia. Using a counterfactual framework we aimed to explore the structure of this paradox as being a consequence of selection bias. Using a case-control study nested in the Icelandic Birth Registry (1309 women), we show how this selection bias can be explored and corrected for. Cases were defined as any case of pregnancy induced hypertension or preeclampsia occurring after 20 weeks' gestation and controls as normotensive mothers who gave birth in the same year. First, we used directed acyclic graphs to illustrate the common bias structure. Second, we used classical logistic regression and mediation analytic methods for dichotomous outcomes to explore the structure of the bias. Lastly, we performed both deterministic and probabilistic sensitivity analysis to estimate the amount of bias due to an uncontrolled confounder and corrected for it. The biased effect of smoking was estimated to reduce the odds of preeclampsia by 28 % (OR 0.72, 95 %CI 0.52, 0.99) and after stratification by gestational age at delivery (<37 vs. ≥37 gestation weeks) by 75 % (OR 0.25, 95 %CI 0.10, 0.68). In a mediation analysis, the natural indirect effect showed and OR > 1, revealing the structure of the paradox. The bias-adjusted estimation of the smoking effect on preeclampsia showed an OR of 1.22 (95 %CI 0.41, 6.53). The smoking-preeclampsia paradox appears to be an example of (1) selection bias most likely caused by studying cases prevalent at birth rather than all incident cases from conception in a pregnancy cohort, (2) omitting important confounders associated with both smoking and preeclampsia (preventing the outcome to develop) and (3) controlling for a collider (gestation weeks at delivery). Future studies need to consider these aspects when studying and interpreting the

Organization of Functional Long-Range Circuits Controlling the Activity of Serotonergic Neurons in the Dorsal Raphe Nucleus.

PubMed

Zhou, Li; Liu, Ming-Zhe; Li, Qing; Deng, Juan; Mu, Di; Sun, Yan-Gang

2017-03-21

Serotonergic neurons play key roles in various biological processes. However, circuit mechanisms underlying tight control of serotonergic neurons remain largely unknown. Here, we systematically investigated the organization of long-range synaptic inputs to serotonergic neurons and GABAergic neurons in the dorsal raphe nucleus (DRN) of mice with a combination of viral tracing, slice electrophysiological, and optogenetic techniques. We found that DRN serotonergic neurons and GABAergic neurons receive largely comparable synaptic inputs from six major upstream brain areas. Upon further analysis of the fine functional circuit structures, we found both bilateral and ipsilateral patterns of topographic connectivity in the DRN for the axons from different inputs. Moreover, the upstream brain areas were found to bidirectionally control the activity of DRN serotonergic neurons by recruiting feedforward inhibition or via a push-pull mechanism. Our study provides a framework for further deciphering the functional roles of long-range circuits controlling the activity of serotonergic neurons in the DRN. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

An Acid Hydrocarbon: A Chemical Paradox

ERIC Educational Resources Information Center

Burke, Jeffrey T.

2004-01-01

The chemical paradox of cyclopentadiene, a hydrocarbon, producing bubbles like a Bronsted acid is observed. The explanation that it is the comparative thermodynamic constancy of the fragrant cyclopentadienyl anion, which produces the powerful effect, resolves the paradox.

Molecular changes in brain aging and Alzheimer’s disease are mirrored in experimentally silenced cortical neuron networks

PubMed Central

Gleichmann, Marc; Zhang, Yongqing; Wood, William H.; Becker, Kevin G.; Mughal, Mohamed R.; Pazin, Michael J.; van Praag, Henriette; Kobilo, Tali; Zonderman, Alan B.; Troncoso, Juan C.; Markesbery, William R.; Mattson, Mark P.

2010-01-01

Activity-dependent modulation of neuronal gene expression promotes neuronal survival and plasticity, and neuronal network activity is perturbed in aging and Alzheimer’s disease (AD). Here we show that cerebral cortical neurons respond to chronic suppression of excitability by downregulating the expression of genes and their encoded proteins involved in inhibitory transmission (GABAergic and somatostatin) and Ca2+ signaling; alterations in pathways involved in lipid metabolism and energy management are also features of silenced neuronal networks. A molecular fingerprint strikingly similar to that of diminished network activity occurs in the human brain during aging and in AD, and opposite changes occur in response to activation of N-methyl-D-aspartate (NMDA) and brain-derived neurotrophic factor (BDNF) receptors in cultured cortical neurons and in mice in response to an enriched environment or electroconvulsive shock. Our findings suggest that reduced inhibitory neurotransmission during aging and in AD may be the result of compensatory responses that, paradoxically, render the neurons vulnerable to Ca2+-mediated degeneration. PMID:20947216

Concentration Dependent Actions of Glucocorticoids on Neuronal Viability and Survival

PubMed Central

Ábrahám, István M; Meerlo, Peter; Luiten, Paul GM

2006-01-01

A growing body of evidence based on experimental data demonstrates that glucocorticoids (GCs) can play a potent role in the survival and death of neurons. However, these observations reflect paradoxical features of GCs, since these adrenal stress hormones are heavily involved in both neurodegenerative and neuroprotective processes. The actual level of GCs appears to have an essential impact in this bimodal action. In the present short review we aim to show the importance of concentration dependent action of GCs on neuronal cell viability and cell survival in the brain. Additionally, we will summarize the possible GC-induced cellular mechanisms at different GC concentrations providing a background for their effect on the fate of nerve cells in conditions that are a challenge to their survival. PMID:18648635

[Effect of 2,3-butanedione monoxime on calcium paradox-induced heart injury in rats].

PubMed

Kong, Ling-Heng; Gu, Xiao-Ming; Su, Xing-Li; Sun, Na; Wei, Ming; Zhu, Juan-Xia; Chang, Pan; Zhou, Jing-Jun

2016-05-01

To investigate the Effect of 2,3-butanedione monoxime (BDM) on calcium paradox-induced heart injury and its underlying mechanisms. Thirty-two adult male SD rats were randomized into 4 groups, namely the control group, BDM treatment control group, calcium paradox group, and BDM treatment group. Isolated Sprague Dawley male rat hearts underwent Langendorff perfusion and the left ventricular pressure (LVP) and left ventricular end-diastolic pressure (LVEDP) were monitored. Left ventricular developed pressure (LVDP) was calculated to evaluate the myocardial performance. Lactate dehydrogenase (LDH) content in the coronary flow was determined. Triphenyltetrazolium chloride staining was used to measure the infarct size, and myocardial cell apoptosis was tested with TUNEL method. Western blotting was used to determine the expression of cleaved caspase-3 and cytochrome c. Compared with the control group, BDM at 20 mmol/L had no effect on cardiac performance, cell death, apoptotic index or the content of LDH, cleaved caspase-3 and cytochrome c at the end of perfusion under control conditions (P>0.05). Calcium paradox treatment significantly decreased the cardiac function and the level of LVDP and induced a larger infarct size (P<0.01), an increased myocardial apoptosis index (P<0.01), and up-regulated expressions of cleaved caspase-3 and cytochrome c (P<0.01). BDM (20 mmol/L) significantly attenuated these effects induced by calcium paradox, and markedly down-regulated the levels of LVEDP and LDH (P<0.01), lowered myocardial apoptosis index, decreased the content of cleaved caspase-3 and cytochrome c (P<0.01), increased LVDP, and reduced the infarct size (P<0.01). BDM suppresses cell apoptosis and contracture and improves heart function and cell survival in rat hearts exposed to calcium paradox, suggesting the value of BDM as an potential drug for myocardial ischemia reperfusion injur.

Control of food intake and energy expenditure by Nos1 neurons of the paraventricular hypothalamus.

PubMed

Sutton, Amy K; Pei, Hongjuan; Burnett, Korri H; Myers, Martin G; Rhodes, Christopher J; Olson, David P

2014-11-12

The paraventricular nucleus of the hypothalamus (PVH) contains a heterogeneous cluster of Sim1-expressing cell types that comprise a major autonomic output nucleus and play critical roles in the control of food intake and energy homeostasis. The roles of specific PVH neuronal subtypes in energy balance have yet to be defined, however. The PVH contains nitric oxide synthase-1 (Nos1)-expressing (Nos1(PVH)) neurons of unknown function; these represent a subset of the larger population of Sim1-expressing PVH (Sim1(PVH)) neurons. To determine the role of Nos1(PVH) neurons in energy balance, we used Cre-dependent viral vectors to both map their efferent projections and test their functional output in mice. Here we show that Nos1(PVH) neurons project to hindbrain and spinal cord regions important for food intake and energy expenditure control. Moreover, pharmacogenetic activation of Nos1(PVH) neurons suppresses feeding to a similar extent as Sim1(PVH) neurons, and increases energy expenditure and activity. Furthermore, we found that oxytocin-expressing PVH neurons (OXT(PVH)) are a subset of Nos1(PVH) neurons. OXT(PVH) cells project to preganglionic, sympathetic neurons in the thoracic spinal cord and increase energy expenditure upon activation, though not to the same extent as Nos1(PVH) neurons; their activation fails to alter feeding, however. Thus, Nos1(PVH) neurons promote negative energy balance through changes in feeding and energy expenditure, whereas OXT(PVH) neurons regulate energy expenditure alone, suggesting a crucial role for non-OXT Nos1(PVH) neurons in feeding regulation. Copyright © 2014 the authors 0270-6474/14/3415306-13$15.00/0.

The Wnt receptor Ryk controls specification of GABAergic neurons versus oligodendrocytes during telencephalon development

PubMed Central

Zhong, Jingyang; Kim, Hyoung-Tai; Lyu, Jungmook; Yoshikawa, Kazuaki; Nakafuku, Masato; Lu, Wange

2011-01-01

GABAergic neurons and oligodendrocytes originate from progenitors within the ventral telencephalon. However, the molecular mechanisms that control neuron-glial cell-fate segregation, especially how extrinsic factors regulate cell-fate changes, are poorly understood. We have discovered that the Wnt receptor Ryk promotes GABAergic neuron production while repressing oligodendrocyte formation in the ventral telencephalon. We demonstrate that Ryk controls the cell-fate switch by negatively regulating expression of the intrinsic oligodendrogenic factor Olig2 while inducing expression of the interneuron fate determinant Dlx2. In addition, we demonstrate that Ryk is required for GABAergic neuron induction and oligodendrogenesis inhibition caused by Wnt3a stimulation. Furthermore, we showed that the cleaved intracellular domain of Ryk is sufficient to regulate the cell-fate switch by regulating the expression of intrinsic cell-fate determinants. These results identify Ryk as a multi-functional receptor that is able to transduce extrinsic cues into progenitor cells, promote GABAergic neuron formation, and inhibit oligodendrogenesis during ventral embryonic brain development. PMID:21205786

Barrier Function-Based Neural Adaptive Control With Locally Weighted Learning and Finite Neuron Self-Growing Strategy.

PubMed

Jia, Zi-Jun; Song, Yong-Duan

2017-06-01

This paper presents a new approach to construct neural adaptive control for uncertain nonaffine systems. By integrating locally weighted learning with barrier Lyapunov function (BLF), a novel control design method is presented to systematically address the two critical issues in neural network (NN) control field: one is how to fulfill the compact set precondition for NN approximation, and the other is how to use varying rather than a fixed NN structure to improve the functionality of NN control. A BLF is exploited to ensure the NN inputs to remain bounded during the entire system operation. To account for system nonlinearities, a neuron self-growing strategy is proposed to guide the process for adding new neurons to the system, resulting in a self-adjustable NN structure for better learning capabilities. It is shown that the number of neurons needed to accomplish the control task is finite, and better performance can be obtained with less number of neurons as compared with traditional methods. The salient feature of the proposed method also lies in the continuity of the control action everywhere. Furthermore, the resulting control action is smooth almost everywhere except for a few time instants at which new neurons are added. Numerical example illustrates the effectiveness of the proposed approach.

Modular control of glutamatergic neuronal identity in C.elegans by distinct homeodomain proteins

PubMed Central

Serrano-Saiz, Esther; Poole, Richard J.; Felton, Terry; Zhang, Feifan; De La Cruz, Estanisla Daniel; Hobert, Oliver

2013-01-01

The choice of using one of many possible neurotransmitter systems is a critical step in defining the identity of an individual neuron type. We show here that the key defining feature of glutamatergic neurons, the vesicular glutamate transporter EAT-4/VGLUT is expressed in 38 of the 118 anatomically defined neuron classes of the C.elegans nervous system. We show that eat-4/VGLUT expression is controlled in a modular manner, with distinct cis-regulatory modules driving expression in distinct glutamatergic neuron classes. We identify 13 different transcription factors, 11 of them homeodomain proteins, that act in specific combinations in 25 different glutamatergic neuron classes to initiate and maintain eat-4/VGLUT expression. We show that the adoption of a glutamatergic phenotype is linked to the adoption of other terminal identity features of a neuron, including cotransmitter phenotypes. Examination of mouse orthologs of these homeodomain proteins resulted in the identification of mouse LHX1 as a regulator of glutamatergic neurons in the brainstem. PMID:24243022

AgRP Neurons Control Systemic Insulin Sensitivity via Myostatin Expression in Brown Adipose Tissue.

PubMed

Steculorum, Sophie M; Ruud, Johan; Karakasilioti, Ismene; Backes, Heiko; Engström Ruud, Linda; Timper, Katharina; Hess, Martin E; Tsaousidou, Eva; Mauer, Jan; Vogt, Merly C; Paeger, Lars; Bremser, Stephan; Klein, Andreas C; Morgan, Donald A; Frommolt, Peter; Brinkkötter, Paul T; Hammerschmidt, Philipp; Benzing, Thomas; Rahmouni, Kamal; Wunderlich, F Thomas; Kloppenburg, Peter; Brüning, Jens C

2016-03-24

Activation of Agouti-related peptide (AgRP) neurons potently promotes feeding, and chronically altering their activity also affects peripheral glucose homeostasis. We demonstrate that acute activation of AgRP neurons causes insulin resistance through impairment of insulin-stimulated glucose uptake into brown adipose tissue (BAT). AgRP neuron activation acutely reprograms gene expression in BAT toward a myogenic signature, including increased expression of myostatin. Interference with myostatin activity improves insulin sensitivity that was impaired by AgRP neurons activation. Optogenetic circuitry mapping reveals that feeding and insulin sensitivity are controlled by both distinct and overlapping projections. Stimulation of AgRP → LHA projections impairs insulin sensitivity and promotes feeding while activation of AgRP → anterior bed nucleus of the stria terminalis (aBNST)vl projections, distinct from AgRP → aBNSTdm projections controlling feeding, mediate the effect of AgRP neuron activation on BAT-myostatin expression and insulin sensitivity. Collectively, our results suggest that AgRP neurons in mice induce not only eating, but also insulin resistance by stimulating expression of muscle-related genes in BAT, revealing a mechanism by which these neurons rapidly coordinate hunger states with glucose homeostasis. Copyright © 2016 Elsevier Inc. All rights reserved.

Slack channels expressed in sensory neurons control neuropathic pain in mice.

PubMed

Lu, Ruirui; Bausch, Anne E; Kallenborn-Gerhardt, Wiebke; Stoetzer, Carsten; Debruin, Natasja; Ruth, Peter; Geisslinger, Gerd; Leffler, Andreas; Lukowski, Robert; Schmidtko, Achim

2015-01-21

Slack (Slo2.2) is a sodium-activated potassium channel that regulates neuronal firing activities and patterns. Previous studies identified Slack in sensory neurons, but its contribution to acute and chronic pain in vivo remains elusive. Here we generated global and sensory neuron-specific Slack mutant mice and analyzed their behavior in various animal models of pain. Global ablation of Slack led to increased hypersensitivity in models of neuropathic pain, whereas the behavior in models of inflammatory and acute nociceptive pain was normal. Neuropathic pain behaviors were also exaggerated after ablation of Slack selectively in sensory neurons. Notably, the Slack opener loxapine ameliorated persisting neuropathic pain behaviors. In conclusion, Slack selectively controls the sensory input in neuropathic pain states, suggesting that modulating its activity might represent a novel strategy for management of neuropathic pain. Copyright © 2015 the authors 0270-6474/15/351125-11$15.00/0.

[Five paradoxes in health promotion].

PubMed

López-Dicastillo, Olga; Canga-Armayor, Navidad; Mujika, Agurtzane; Pardavila-Belio, Miren Idoia; Belintxon, Maider; Serrano-Monzó, Inmaculada; Pumar-Méndez, María J

The World Health Organization states that health promotion is a key strategy to improve health, and it is conceived as a global process of enabling people to increase control over, and to improve, their health. Health promotion does not focus solely on empowering individuals dealing with their knowledge, attitudes and skills, but it also takes political, social, economic and environmental aspects influencing health and wellbeing into account. The complexity of applying these concepts is reflected in the five paradoxes in health promotion; these arise in between the rhetoric in health promotion and implementation. The detected paradoxes which are described herein involve the patient versus the person, the individual versus the group, disease professionals versus health professionals, disease indicators versus health indicators, and health as an expense versus health as an investment. Making these contradictions explicit can help determine why it is so complex to put the concepts related to health promotion into practice. It can also help to put forward aspects that need further work if health promotion is to put into practice. Copyright © 2017 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.

Mathematical background of Parrondo's paradox

NASA Astrophysics Data System (ADS)

Behrends, Ehrhard

2004-05-01

Parrondo's paradox states that there are losing gambling games which, when being combined stochastically or in a suitable deterministic way, give rise to winning games. Here we investigate the probabilistic background. We show how the properties of the equilibrium distributions of the Markov chains under consideration give rise to the paradoxical behavior, and we provide methods how to find the best a priori strategies.

Spontaneous activity of single neurones in the hypothalamus of rabbits during sleep and waking

PubMed Central

Findlay, Alan L. R.; Hayward, James N.

1969-01-01

1. A method is described for recording from single cells in the hypothalamus of unanaesthetized freely moving rabbits. Behaviour, bodily movement, skin and brain temperatures and e.e.g. were monitored. 2. Patterns of unit firing during slow sleep, paradoxical sleep and waking were studied in several regions of the hypothalamus, thalamus and in the septum. 3. Of the 144 cells analysed from waking to slow sleep, fifty-six (39%) decreased mean firing rates, thirty (21%) increased spike discharges and fifty-eight (40%) showed no marked change. Dorsal hypothalamic and massa intermedia thalamic cells fired in brief high frequency clusters during slow sleep with a characteristic `bimodal' interspike interval histogram. Waking and paradoxical sleep abolished these cluster discharges with a concomitant change to an `asymmetric' histogram. 4. Of the thirty-two cells observed during the three states of waking, slow sleep and paradoxical sleep, a majority (twenty-five or 78%) showed their highest rates of spontaneous discharge during paradoxical sleep. Discharge rates of cells sometimes changed in the course of paradoxical sleep according to the presence or absence of phasic events such as myoclonic motor activity. Two hypothalmic cells were almost totally arrested during paradoxical sleep. 5. Analysis of unit firing rates during spontaneous rises in brain temperature during waking and paradoxical sleep revealed that a majority of the neurones (22/24) changed their discharge rates in relation to behaviour rather than to brain temperature. Two cells did appear to respond specifically to the central thermal stimulus. 6. Hypothalamic cells do not behave as a homogeneous population in relation to changes in the state of arousal of the rabbit. Spontaneous changes in cell discharge related to sleep-waking behaviour must be considered in any interpretation of hypothalamic unit activity as related to neuroendocrine or autonomic mechanisms. PMID:4304342

FlyMAD: rapid thermogenetic control of neuronal activity in freely walking Drosophila.

PubMed

Bath, Daniel E; Stowers, John R; Hörmann, Dorothea; Poehlmann, Andreas; Dickson, Barry J; Straw, Andrew D

2014-07-01

Rapidly and selectively modulating the activity of defined neurons in unrestrained animals is a powerful approach in investigating the circuit mechanisms that shape behavior. In Drosophila melanogaster, temperature-sensitive silencers and activators are widely used to control the activities of genetically defined neuronal cell types. A limitation of these thermogenetic approaches, however, has been their poor temporal resolution. Here we introduce FlyMAD (the fly mind-altering device), which allows thermogenetic silencing or activation within seconds or even fractions of a second. Using computer vision, FlyMAD targets an infrared laser to freely walking flies. As a proof of principle, we demonstrated the rapid silencing and activation of neurons involved in locomotion, vision and courtship. The spatial resolution of the focused beam enabled preferential targeting of neurons in the brain or ventral nerve cord. Moreover, the high temporal resolution of FlyMAD allowed us to discover distinct timing relationships for two neuronal cell types previously linked to courtship song.

Stokes paradox in electronic Fermi liquids

NASA Astrophysics Data System (ADS)

Lucas, Andrew

2017-03-01

The Stokes paradox is the statement that in a viscous two-dimensional fluid, the "linear response" problem of fluid flow around an obstacle is ill posed. We present a simple consequence of this paradox in the hydrodynamic regime of a Fermi liquid of electrons in two-dimensional metals. Using hydrodynamics and kinetic theory, we estimate the contribution of a single cylindrical obstacle to the global electrical resistance of a material, within linear response. Momentum relaxation, present in any realistic electron liquid, resolves the classical paradox. Nonetheless, this paradox imprints itself in the resistance, which can be parametrically larger than predicted by Ohmic transport theory. We find a remarkably rich set of behaviors, depending on whether or not the quasiparticle dynamics in the Fermi liquid should be treated as diffusive, hydrodynamic, or ballistic on the length scale of the obstacle. We argue that all three types of behavior are observable in present day experiments.

Ultrastructure of spines and associated terminals on brainstem neurons controlling auditory input

PubMed Central

Brown, M. Christian; Lee, Daniel J.; Benson, Thane E.

2013-01-01

Spines are unique cellular appendages that isolate synaptic input to neurons and play a role in synaptic plasticity. Using the electron microscope, we studied spines and their associated synaptic terminals on three groups of brainstem neurons: tensor tympani motoneurons, stapedius motoneurons, and medial olivocochlear neurons, all of which exert reflexive control of processes in the auditory periphery. These spines are generally simple in shape; they are infrequent and found on the somata as well as the dendrites. Spines do not differ in volume among the three groups of neurons. In all cases, the spines are associated with a synaptic terminal that engulfs the spine rather than abuts its head. The positions of the synapses are variable, and some are found at a distance from the spine, suggesting that the isolation of synaptic input is of diminished importance for these spines. Each group of neurons receives three common types of synaptic terminals. The type of terminal associated with spines of the motoneurons contains pleomorphic vesicles, whereas the type associated with spines of olivocochlear neurons contains large round vesicles. Thus, spine-associated terminals in the motoneurons appear to be associated with inhibitory processes but in olivocochlear neurons they are associated with excitatory processes. PMID:23602963

Can simple rules control development of a pioneer vertebrate neuronal network generating behavior?

PubMed

Roberts, Alan; Conte, Deborah; Hull, Mike; Merrison-Hort, Robert; al Azad, Abul Kalam; Buhl, Edgar; Borisyuk, Roman; Soffe, Stephen R

2014-01-08

How do the pioneer networks in the axial core of the vertebrate nervous system first develop? Fundamental to understanding any full-scale neuronal network is knowledge of the constituent neurons, their properties, synaptic interconnections, and normal activity. Our novel strategy uses basic developmental rules to generate model networks that retain individual neuron and synapse resolution and are capable of reproducing correct, whole animal responses. We apply our developmental strategy to young Xenopus tadpoles, whose brainstem and spinal cord share a core vertebrate plan, but at a tractable complexity. Following detailed anatomical and physiological measurements to complete a descriptive library of each type of spinal neuron, we build models of their axon growth controlled by simple chemical gradients and physical barriers. By adding dendrites and allowing probabilistic formation of synaptic connections, we reconstruct network connectivity among up to 2000 neurons. When the resulting "network" is populated by model neurons and synapses, with properties based on physiology, it can respond to sensory stimulation by mimicking tadpole swimming behavior. This functioning model represents the most complete reconstruction of a vertebrate neuronal network that can reproduce the complex, rhythmic behavior of a whole animal. The findings validate our novel developmental strategy for generating realistic networks with individual neuron- and synapse-level resolution. We use it to demonstrate how early functional neuronal connectivity and behavior may in life result from simple developmental "rules," which lay out a scaffold for the vertebrate CNS without specific neuron-to-neuron recognition.

Activation state of the hyperpolarization-activated current modulates temperature-sensitivity of firing in locus coeruleus neurons from bullfrogs.

PubMed

Santin, Joseph M; Hartzler, Lynn K

2015-06-15

Locus coeruleus neurons of anuran amphibians contribute to breathing control and have spontaneous firing frequencies that, paradoxically, increase with cooling. We previously showed that cooling inhibits a depolarizing membrane current, the hyperpolarization-activated current (I h) in locus coeruleus neurons from bullfrogs, Lithobates catesbeianus (Santin JM, Watters KC, Putnam RW, Hartzler LK. Am J Physiol Regul Integr Comp Physiol 305: R1451-R1464, 2013). This suggests an unlikely role for I h in generating cold activation, but led us to hypothesize that inhibition of I h by cooling functions as a physiological brake to limit the cold-activated response. Using whole cell electrophysiology in brain slices, we employed 2 mM Cs(+) (an I h antagonist) to isolate the role of I h in spontaneous firing and cold activation in neurons recorded with either control or I h agonist (cyclic AMP)-containing artificial intracellular fluid. I h did not contribute to the membrane potential (V m) and spontaneous firing at 20°C. Although voltage-clamp analysis confirmed that cooling inhibits I h, its lack of involvement in setting baseline firing and V m precluded its ability to regulate cold activation as hypothesized. In contrast, neurons dialyzed with cAMP exhibited greater baseline firing frequencies at 20°C due to I h activation. Our hypothesis was supported when the starting level of I h was enhanced by elevating cAMP because cold activation was converted to more ordinary cold inhibition. These findings indicate that situations leading to enhancement of I h facilitate firing at 20°C, yet the hyperpolarization associated with inhibiting a depolarizing cation current by cooling blunts the net V m response to cooling to oppose normal cold-depolarizing factors. This suggests that the influence of I h activation state on neuronal firing varies in the poikilothermic neuronal environment. Copyright © 2015 the American Physiological Society.

Training in cortical control of neuroprosthetic devices improves signal extraction from small neuronal ensembles.

PubMed

Helms Tillery, S I; Taylor, D M; Schwartz, A B

2003-01-01

We have recently developed a closed-loop environment in which we can test the ability of primates to control the motion of a virtual device using ensembles of simultaneously recorded neurons /29/. Here we use a maximum likelihood method to assess the information about task performance contained in the neuronal ensemble. We trained two animals to control the motion of a computer cursor in three dimensions. Initially the animals controlled cursor motion using arm movements, but eventually they learned to drive the cursor directly from cortical activity. Using a population vector (PV) based upon the relation between cortical activity and arm motion, the animals were able to control the cursor directly from the brain in a closed-loop environment, but with difficulty. We added a supervised learning method that modified the parameters of the PV according to task performance (adaptive PV), and found that animals were able to exert much finer control over the cursor motion from brain signals. Here we describe a maximum likelihood method (ML) to assess the information about target contained in neuronal ensemble activity. Using this method, we compared the information about target contained in the ensemble during arm control, during brain control early in the adaptive PV, and during brain control after the adaptive PV had settled and the animal could drive the cursor reliably and with fine gradations. During the arm-control task, the ML was able to determine the target of the movement in as few as 10% of the trials, and as many as 75% of the trials, with an average of 65%. This average dropped when the animals used a population vector to control motion of the cursor. On average we could determine the target in around 35% of the trials. This low percentage was also reflected in poor control of the cursor, so that the animal was unable to reach the target in a large percentage of trials. Supervised adjustment of the population vector parameters produced new weighting

Dual PDF signaling pathways reset clocks via TIMELESS and acutely excite target neurons to control circadian behavior.

PubMed

Seluzicki, Adam; Flourakis, Matthieu; Kula-Eversole, Elzbieta; Zhang, Luoying; Kilman, Valerie; Allada, Ravi

2014-03-01

Molecular circadian clocks are interconnected via neural networks. In Drosophila, PIGMENT-DISPERSING FACTOR (PDF) acts as a master network regulator with dual functions in synchronizing molecular oscillations between disparate PDF(+) and PDF(-) circadian pacemaker neurons and controlling pacemaker neuron output. Yet the mechanisms by which PDF functions are not clear. We demonstrate that genetic inhibition of protein kinase A (PKA) in PDF(-) clock neurons can phenocopy PDF mutants while activated PKA can partially rescue PDF receptor mutants. PKA subunit transcripts are also under clock control in non-PDF DN1p neurons. To address the core clock target of PDF, we rescued per in PDF neurons of arrhythmic per⁰¹ mutants. PDF neuron rescue induced high amplitude rhythms in the clock component TIMELESS (TIM) in per-less DN1p neurons. Complete loss of PDF or PKA inhibition also results in reduced TIM levels in non-PDF neurons of per⁰¹ flies. To address how PDF impacts pacemaker neuron output, we focally applied PDF to DN1p neurons and found that it acutely depolarizes and increases firing rates of DN1p neurons. Surprisingly, these effects are reduced in the presence of an adenylate cyclase inhibitor, yet persist in the presence of PKA inhibition. We have provided evidence for a signaling mechanism (PKA) and a molecular target (TIM) by which PDF resets and synchronizes clocks and demonstrates an acute direct excitatory effect of PDF on target neurons to control neuronal output. The identification of TIM as a target of PDF signaling suggests it is a multimodal integrator of cell autonomous clock, environmental light, and neural network signaling. Moreover, these data reveal a bifurcation of PKA-dependent clock effects and PKA-independent output effects. Taken together, our results provide a molecular and cellular basis for the dual functions of PDF in clock resetting and pacemaker output.

Dual PDF Signaling Pathways Reset Clocks Via TIMELESS and Acutely Excite Target Neurons to Control Circadian Behavior

PubMed Central

Seluzicki, Adam; Flourakis, Matthieu; Kula-Eversole, Elzbieta; Zhang, Luoying; Kilman, Valerie; Allada, Ravi

2014-01-01

Molecular circadian clocks are interconnected via neural networks. In Drosophila, PIGMENT-DISPERSING FACTOR (PDF) acts as a master network regulator with dual functions in synchronizing molecular oscillations between disparate PDF(+) and PDF(−) circadian pacemaker neurons and controlling pacemaker neuron output. Yet the mechanisms by which PDF functions are not clear. We demonstrate that genetic inhibition of protein kinase A (PKA) in PDF(−) clock neurons can phenocopy PDF mutants while activated PKA can partially rescue PDF receptor mutants. PKA subunit transcripts are also under clock control in non-PDF DN1p neurons. To address the core clock target of PDF, we rescued per in PDF neurons of arrhythmic per01 mutants. PDF neuron rescue induced high amplitude rhythms in the clock component TIMELESS (TIM) in per-less DN1p neurons. Complete loss of PDF or PKA inhibition also results in reduced TIM levels in non-PDF neurons of per01 flies. To address how PDF impacts pacemaker neuron output, we focally applied PDF to DN1p neurons and found that it acutely depolarizes and increases firing rates of DN1p neurons. Surprisingly, these effects are reduced in the presence of an adenylate cyclase inhibitor, yet persist in the presence of PKA inhibition. We have provided evidence for a signaling mechanism (PKA) and a molecular target (TIM) by which PDF resets and synchronizes clocks and demonstrates an acute direct excitatory effect of PDF on target neurons to control neuronal output. The identification of TIM as a target of PDF signaling suggests it is a multimodal integrator of cell autonomous clock, environmental light, and neural network signaling. Moreover, these data reveal a bifurcation of PKA-dependent clock effects and PKA-independent output effects. Taken together, our results provide a molecular and cellular basis for the dual functions of PDF in clock resetting and pacemaker output. PMID:24643294

New Paradoxes of Risky Decision Making

ERIC Educational Resources Information Center

Birnbaum, Michael H.

2008-01-01

During the last 25 years, prospect theory and its successor, cumulative prospect theory, replaced expected utility as the dominant descriptive theories of risky decision making. Although these models account for the original Allais paradoxes, 11 new paradoxes show where prospect theories lead to self-contradiction or systematic false predictions.…

Virtue Acquisition: The Paradox of Striving

ERIC Educational Resources Information Center

Snow, Nancy

2016-01-01

Aristotelian-inspired accounts of virtue acquisition stress guided practice and habituated action to develop virtue. This emphasis on action can lead to the "paradox of striving". The paradox occurs when we try too hard to act well and thereby spoil our efforts. I identify four forms of striving--forcing, impulsivity, overthinking, and…

Unintended consequence of managing the coupled humans and water: the irrigation efficiency paradox

NASA Astrophysics Data System (ADS)

Liu, Y.

2015-12-01

Water shortage most severely restricts the socio-economic development of many arid and semi-arid regions in the world, for which water-saving technology is believed to be an effective solution. However, as a realworld case, the total water consumption of Xinjiang Uygur Autonomous Region of China continued to increase as irrigation efficiency dramatically improved through the application of water-saving technology in the study period 1998-2010. This phenomenon, known as the irrigation efficiency paradox or Jevons paradox, is interpreted as an economic rebound effect. In this study, we explore the dynamic feedbacks between humans and water in this paradox through a socio-hydrological perspective. We analyze the co-evolutionary trajectory of coupled human-water dynamics from 1950 to 2010 to provide it a general context. A conceptual socio-hydrological model based on five key elements, namely, irrigation land, water-saving technology, water consumption, societal sensitivity to water scarcity, and the policy mix, is constructed. The policy mix to be adopted is determined by a social decision-making process mainly based on the societal sensitivity, which reflects the societal preference on two sorts of policies: (i) irrigation land control and (ii) water-saving technology promotion. Modeling results verify the hypothesized mechanism by successfully reproducing the observed dynamics including the emergence of the efficiency paradox. Our analysis indicates that the implementation of more adaptive rules may even eliminate the paradox. The effects of different initial policy mixes are also explored, and the results show that land control policies should be given equal priority when dealing with water scarcity. These findings point to a double-helix-type co-evolution of humans and water.

Photodynamic injury of isolated crayfish neuron and surrounding glial cells: the role of p53

NASA Astrophysics Data System (ADS)

Sharifulina, S. A.; Uzdensky, A. B.

2015-03-01

The pro-apoptotic transcription factor p53 is involved in cell responses to injurious impacts. Using its inhibitor pifithrin- α and activators tenovin-1, RITA and WR-1065, we studied its potential participation in inactivation and death of isolated crayfish mechanoreceptor neuron and satellite glial cells induced by photodynamic treatment, a strong inducer of oxidative stress. In dark, p53 activation by tenovin-1 or WR-1065 shortened activity of isolated neurons. Tenovin-1 and WR-1065 induced apoptosis of glial cells, whereas pifithrin-α was anti-apoptotic. Therefore, p53 mediated glial apoptosis and suppression of neuronal activity after axotomy. Tenovin-1 but not other p53 modulators induced necrosis of axotomized neurons and surrounding glia, possibly, through p53-independent pathway. Under photodynamic treatment, p53 activators tenovin-1 and RITA enhanced glial apoptosis indicating the pro-apoptotic activity of p53. Photoinduced necrosis of neurons and glia was suppressed by tenovin-1 and, paradoxically, by pifithrin-α. Modulation of photoinduced changes in the neuronal activity and necrosis of neurons and glia was possibly p53-independent. The different effects of p53 modulators on neuronal and glial responses to axotomy and photodynamic impact were apparently associated with different signaling pathways in neurons and glial cells.

Paradox, reprimand and extinction in adults with mental handicap.

PubMed

Wood, V E; Chamove, A S

1991-08-01

To assess the efficacy of paradoxical directives, levels of challenging behaviour during 2 weeks of paradox, reprimand and extinction were compared with baseline levels in four adults with mental handicaps attending a day centre. Paradox was the most effective procedure for reducing the frequency and severity of challenging behaviour by an average of over 70% by the end of 2 weeks and up to 90% in certain subjects; extinction was least effective. Paradox was most effective with more defiant subjects, when staff rated treatment success as low, when improvement using extinction and reprimand was poorest, and in reducing aggressive behaviour. The present authors suggest the overjustification effect offers an explanation for the effects of paradox.

Automatic parameter estimation of multicompartmental neuron models via minimization of trace error with control adjustment.

PubMed

Brookings, Ted; Goeritz, Marie L; Marder, Eve

2014-11-01

We describe a new technique to fit conductance-based neuron models to intracellular voltage traces from isolated biological neurons. The biological neurons are recorded in current-clamp with pink (1/f) noise injected to perturb the activity of the neuron. The new algorithm finds a set of parameters that allows a multicompartmental model neuron to match the recorded voltage trace. Attempting to match a recorded voltage trace directly has a well-known problem: mismatch in the timing of action potentials between biological and model neuron is inevitable and results in poor phenomenological match between the model and data. Our approach avoids this by applying a weak control adjustment to the model to promote alignment during the fitting procedure. This approach is closely related to the control theoretic concept of a Luenberger observer. We tested this approach on synthetic data and on data recorded from an anterior gastric receptor neuron from the stomatogastric ganglion of the crab Cancer borealis. To test the flexibility of this approach, the synthetic data were constructed with conductance models that were different from the ones used in the fitting model. For both synthetic and biological data, the resultant models had good spike-timing accuracy. Copyright © 2014 the American Physiological Society.

Expiratory muscle control during vomiting - Role of brain stem expiratory neurons

NASA Technical Reports Server (NTRS)

Miller, A. D.; Tan, L. K.

1987-01-01

The neural mechanisms controlling the muscles involved during vomiting were examined using decerebrated cats. In one experiment, the activity of the ventral respiratory group (VRG) expiratory (E) neurons was recorded during induced 'fictive vomiting' (i.e., a series of bursts of coactivation of abdominal and phrenic nerves that would be expected to produce expulsion in unparalyzed animals) and vomiting. In a second, abdominal muscle electromyographic and nerve activity were compared before and after sectioning the axons of descending VRG E neurons as they cross the midline between C1 and the obex (the procedure that is known to abolish expiratory modulation of internal intercostal muscle activity). The results of the study indicate that the abdominal muscles are controlled differently during respiration and vomiting.

Optimal experience among teachers: new insights into the work paradox.

PubMed

Bassi, Marta; Delle Fave, Antonella

2012-01-01

Several studies highlighted that individuals perceive work as an opportunity for flow or optimal experience, but not as desirable and pleasant. This finding was defined as the work paradox. The present study addressed this issue among teachers from the perspective of self-determination theory, investigating work-related intrinsic and extrinsic motivation, as well as autonomous and controlled behavior regulation. In Study 1, 14 teachers were longitudinally monitored with Experience Sampling Method for one work week. In Study 2, 184 teachers were administered Flow Questionnaire and Work Preference Inventory, respectively investigating opportunities for optimal experience, and motivational orientations at work. Results showed that work-related optimal experiences were associated with both autonomous regulation and with controlled regulation. Moreover, teachers reported both intrinsic and extrinsic motivation at work, with a prevailing intrinsic orientation. Findings provide novel insights on the work paradox, and suggestions for teachers' well-being promotion.

A New Population of Parvocellular Oxytocin Neurons Controlling Magnocellular Neuron Activity and Inflammatory Pain Processing

PubMed Central

Eliava, Marina; Melchior, Meggane; Knobloch-Bollmann, H. Sophie; Wahis, Jérôme; Gouveia, Miriam da Silva; Tang, Yan; Ciobanu, Alexandru Cristian; del Rio, Rodrigo Triana; Roth, Lena C.; Althammer, Ferdinand; Chavant, Virginie; Goumon, Yannick; Gruber, Tim; Petit-Demoulière, Nathalie; Busnelli, Marta; Chini, Bice; Tan, Linette L.; Mitre, Mariela; Froemke, Robert C.; Chao, Moses V.; Giese, Günter; Sprengel, Rolf; Kuner, Rohini; Poisbeau, Pierrick; Seeburg, Peter H.; Stoop, Ron; Charlet, Alexandre; Grinevich, Valery

2017-01-01

SUMMARY Oxytocin (OT) is a neuropeptide elaborated by the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei. Magnocellular OT neurons of these nuclei innervate numerous forebrain regions and release OT into the blood from the posterior pituitary. The PVN also harbors parvocellular OT cells that project to the brainstem and spinal cord, but their function has not been directly assessed. Here, we identified a subset of approximately 30 parvocellular OT neurons, with collateral projections onto magnocellular OT neurons and neurons of deep layers of the spinal cord. Evoked OT release from these OT neurons suppresses nociception and promotes analgesia in an animal model of inflammatory pain. Our findings identify a new population of OT neurons that modulates nociception in a two tier process: (1) directly by release of OT from axons onto sensory spinal cord neurons and inhibiting their activity and (2) indirectly by stimulating OT release from SON neurons into the periphery. PMID:26948889

A New Population of Parvocellular Oxytocin Neurons Controlling Magnocellular Neuron Activity and Inflammatory Pain Processing.

PubMed

Eliava, Marina; Melchior, Meggane; Knobloch-Bollmann, H Sophie; Wahis, Jérôme; da Silva Gouveia, Miriam; Tang, Yan; Ciobanu, Alexandru Cristian; Triana Del Rio, Rodrigo; Roth, Lena C; Althammer, Ferdinand; Chavant, Virginie; Goumon, Yannick; Gruber, Tim; Petit-Demoulière, Nathalie; Busnelli, Marta; Chini, Bice; Tan, Linette L; Mitre, Mariela; Froemke, Robert C; Chao, Moses V; Giese, Günter; Sprengel, Rolf; Kuner, Rohini; Poisbeau, Pierrick; Seeburg, Peter H; Stoop, Ron; Charlet, Alexandre; Grinevich, Valery

2016-03-16

Oxytocin (OT) is a neuropeptide elaborated by the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei. Magnocellular OT neurons of these nuclei innervate numerous forebrain regions and release OT into the blood from the posterior pituitary. The PVN also harbors parvocellular OT cells that project to the brainstem and spinal cord, but their function has not been directly assessed. Here, we identified a subset of approximately 30 parvocellular OT neurons, with collateral projections onto magnocellular OT neurons and neurons of deep layers of the spinal cord. Evoked OT release from these OT neurons suppresses nociception and promotes analgesia in an animal model of inflammatory pain. Our findings identify a new population of OT neurons that modulates nociception in a two tier process: (1) directly by release of OT from axons onto sensory spinal cord neurons and inhibiting their activity and (2) indirectly by stimulating OT release from SON neurons into the periphery. Copyright © 2016 Elsevier Inc. All rights reserved.

Role of Non-Neuronal Cells in Body Weight and Appetite Control

PubMed Central

Argente-Arizón, Pilar; Freire-Regatillo, Alejandra; Argente, Jesús; Chowen, Julie A.

2015-01-01

The brain is composed of neurons and non-neuronal cells, with the latter encompassing glial, ependymal and endothelial cells, as well as pericytes and progenitor cells. Studies aimed at understanding how the brain operates have traditionally focused on neurons, but the importance of non-neuronal cells has become increasingly evident. Once relegated to supporting roles, it is now indubitable that these diverse cell types are fundamental for brain development and function, including that of metabolic circuits, and they may play a significant role in obesity onset and complications. They participate in processes of neurogenesis, synaptogenesis, and synaptic plasticity of metabolic circuits both during development and in adulthood. Some glial cells, such as tanycytes and astrocytes, transport circulating nutrients and metabolic factors that are fundamental for neuronal viability and activity into and within the hypothalamus. All of these cell types express receptors for a variety of metabolic factors and hormones, suggesting that they participate in metabolic function. They are the first line of defense against any assault to neurons. Indeed, microglia and astrocytes participate in the hypothalamic inflammatory response to high fat diet (HFD)-induced obesity, with this process contributing to inflammatory-related insulin and leptin resistance. Moreover, HFD-induced obesity and hyperleptinemia modify hypothalamic astroglial morphology, which is associated with changes in the synaptic inputs to neuronal metabolic circuits. Astrocytic contact with the microvasculature is increased by HFD intake and this could modify nutrient/hormonal uptake into the brain. In addition, progenitor cells in the hypothalamus are now known to have the capacity to renew metabolic circuits, and this can be affected by HFD intake and obesity. Here, we discuss our current understanding of how non-neuronal cells participate in physiological and physiopathological metabolic control. PMID:25859240

The Policy Maker's Anguish: Regulating Personal Data Behavior Between Paradoxes and Dilemmas

NASA Astrophysics Data System (ADS)

Compañó, Ramón; Lusoli, Wainer

Regulators in Europe and elsewhere are paying great attention to identity, privacy and trust in online and converging environments. Appropriate regulation of identity in a ubiquitous information environment is seen as one of the major drivers of the future Internet economy. Regulation of personal identity data has come to the fore including mapping conducted on digital personhood by the OECD; work on human rights and profiling by the Council of Europe andmajor studies by the European Commission with regard to self-regulation in the privacy market, electronic identity technical interoperability and enhanced safety for young people. These domains overlap onto an increasingly complex model of regulation of individuals' identity management, online and offline. This chapter argues that policy makers struggle to deal with issues concerning electronic identity, due to the apparently irrational and unpredictable behavior of users when engaging in online interactions involving identity management. Building on empirical survey evidence from four EU countries, we examine the first aspect in detail - citizens' management of identity in a digital environment. We build on data from a large scale (n = 5,265) online survey of attitudes to electronic identity among young Europeans (France, Germany, Spain, UK) conducted in August 2008. The survey asked questions about perceptions and acceptance of risks, general motivations, attitudes and behaviors concerning electronic identity. Four behavioral paradoxes are identified in the analysis: a privacy paradox (to date well known), but also a control paradox, a responsibility paradox and an awareness paradox. The chapter then examines the paradoxes in relation of three main policy dilemmas framing the debate on digital identity. The paper concludes by arguing for an expanded identity debate spanning policy circles and the engineering community.

Habituated Reason: Aristotle and the "Paradox of Moral Education"

ERIC Educational Resources Information Center

Kristjansson, Kristjan

2006-01-01

R.S. Peters coined the term "paradox of moral education". In this article, the author identifies two subordinate paradoxes: how habituated reason is psychologically possible and how heteronomously formed autonomy is morally/politically possible and justifiable. He sketches possible Aristotelian solutions of those paradoxes and argues that for…

The ADAR RNA editing enzyme controls neuronal excitability in Drosophila melanogaster

PubMed Central

Li, Xianghua; Overton, Ian M.; Baines, Richard A.; Keegan, Liam P.; O’Connell, Mary A.

2014-01-01

RNA editing by deamination of specific adenosine bases to inosines during pre-mRNA processing generates edited isoforms of proteins. Recoding RNA editing is more widespread in Drosophila than in vertebrates. Editing levels rise strongly at metamorphosis, and Adar5G1 null mutant flies lack editing events in hundreds of CNS transcripts; mutant flies have reduced viability, severely defective locomotion and age-dependent neurodegeneration. On the other hand, overexpressing an adult dADAR isoform with high enzymatic activity ubiquitously during larval and pupal stages is lethal. Advantage was taken of this to screen for genetic modifiers; Adar overexpression lethality is rescued by reduced dosage of the Rdl (Resistant to dieldrin), gene encoding a subunit of inhibitory GABA receptors. Reduced dosage of the Gad1 gene encoding the GABA synthetase also rescues Adar overexpression lethality. Drosophila Adar5G1 mutant phenotypes are ameliorated by feeding GABA modulators. We demonstrate that neuronal excitability is linked to dADAR expression levels in individual neurons; Adar-overexpressing larval motor neurons show reduced excitability whereas Adar5G1 null mutant or targeted Adar knockdown motor neurons exhibit increased excitability. GABA inhibitory signalling is impaired in human epileptic and autistic conditions, and vertebrate ADARs may have a relevant evolutionarily conserved control over neuronal excitability. PMID:24137011

Implementing Parrondo's paradox with two-coin quantum walks

NASA Astrophysics Data System (ADS)

Rajendran, Jishnu; Benjamin, Colin

2018-02-01

Parrondo's paradox is ubiquitous in games, ratchets and random walks. The apparent paradox, devised by J. M. R. Parrondo, that two losing games A and B can produce a winning outcome has been adapted in many physical and biological systems to explain their working. However, proposals on demonstrating Parrondo's paradox using quantum walks failed for a large number of steps. In this work, we show that instead of a single coin if we consider a two-coin initial state which may or may not be entangled, we can observe a genuine Parrondo's paradox with quantum walks. Furthermore, we focus on reasons for this and pin down the asymmetry in initial two-coin state or asymmetry in shift operator, either of which is necessary for observing a genuine Parrondo's paradox. We extend our work to a three-coin initial state too with similar results. The implications of our work for observing quantum ratchet-like behaviour using quantum walks are also discussed.

A microfluidic platform for controlled biochemical stimulation of twin neuronal networks.

PubMed

Biffi, Emilia; Piraino, Francesco; Pedrocchi, Alessandra; Fiore, Gianfranco B; Ferrigno, Giancarlo; Redaelli, Alberto; Menegon, Andrea; Rasponi, Marco

2012-06-01

Spatially and temporally resolved delivery of soluble factors is a key feature for pharmacological applications. In this framework, microfluidics coupled to multisite electrophysiology offers great advantages in neuropharmacology and toxicology. In this work, a microfluidic device for biochemical stimulation of neuronal networks was developed. A micro-chamber for cell culturing, previously developed and tested for long term neuronal growth by our group, was provided with a thin wall, which partially divided the cell culture region in two sub-compartments. The device was reversibly coupled to a flat micro electrode array and used to culture primary neurons in the same microenvironment. We demonstrated that the two fluidically connected compartments were able to originate two parallel neuronal networks with similar electrophysiological activity but functionally independent. Furthermore, the device allowed to connect the outlet port to a syringe pump and to transform the static culture chamber in a perfused one. At 14 days invitro, sub-networks were independently stimulated with a test molecule, tetrodotoxin, a neurotoxin known to block action potentials, by means of continuous delivery. Electrical activity recordings proved the ability of the device configuration to selectively stimulate each neuronal network individually. The proposed microfluidic approach represents an innovative methodology to perform biological, pharmacological, and electrophysiological experiments on neuronal networks. Indeed, it allows for controlled delivery of substances to cells, and it overcomes the limitations due to standard drug stimulation techniques. Finally, the twin network configuration reduces biological variability, which has important outcomes on pharmacological and drug screening.

Orexin Neurons Are Necessary for the Circadian Control of REM Sleep

PubMed Central

Kantor, Sandor; Mochizuki, Takatoshi; Janisiewicz, Agnieszka M.; Clark, Erika; Nishino, Seiji; Scammell, Thomas E.

2009-01-01

Study Objectives: The orexin-producing neurons are hypothesized to be essential for the circadian control of sleep/wake behavior, but it remains unknown whether these rhythms are mediated by the orexin peptides or by other signaling molecules released by these neurons such as glutamate or dynorphin. To determine the roles of these neurotransmitters, we examined the circadian rhythms of sleep/wake behavior in mice lacking the orexin neurons (ataxin-3 [Atx] mice) and mice lacking just the orexin neuropeptides (orexin knockout [KO] mice). Design: We instrumented mice for recordings of sleep-wake behavior, locomotor activity (LMA), and body temperature (Tb) and recorded behavior after 6 days in constant darkness. Results: The amplitude of the rapid eye movement (REM) sleep rhythm was substantially reduced in Atx mice but preserved in orexin KO mice. This blunted rhythm in Atx mice was caused by an increase in the amount of REM sleep during the subjective night (active period) due to more transitions into REM sleep and longer REM sleep episodes. In contrast, the circadian variations of Tb, LMA, Wake, non-REM sleep, and cataplexy were normal, suggesting that the circadian timekeeping system and other output pathways are intact in both Atx and KO mice. Conclusions: These results indicate that the orexin neurons are necessary for the circadian suppression of REM sleep. Blunting of the REM sleep rhythm in Atx mice but not in orexin KO mice suggests that other signaling molecules such as dynorphin or glutamate may act in concert with orexins to suppress REM sleep during the active period. Citation: Kantor S; Mochizuki T; Janisiewicz AM; Clark E; Nishino S; Scammell TE. Orexin neurons are necessary for the circadian control of REM sleep. SLEEP 2009;32(9):1127-1134. PMID:19750917

Contributions of 5-HT neurons to respiratory control: neuromodulatory and trophic effects.

PubMed

Hodges, Matthew R; Richerson, George B

2008-12-10

Serotonin (5-hydroxytryptamine; 5-HT) is a neurotransmitter produced by a small number of neurons in the midbrain, pons and medulla. These neurons project widely throughout the neuraxis, where they release 5-HT and co-localized neuropeptides such as substance P (SP) and thyrotropin-releasing hormone (TRH). Each of these chemicals produce effects largely through G protein-coupled receptors, second messenger systems and subsequent neuromodulatory effects on target neurons. Emerging evidence suggests that 5-HT has additional modes of action during development and in adult mammals, including trophic effects (neurogenesis, cell differentiation, proliferation, migration and maturation) and influences on synaptic plasticity. Here, we discuss some of the neuromodulatory and trophic roles of 5-HT in general and in the context of respiratory control, as well as the regulation of release of modulatory neurotransmitters from 5-HT neurons. Future directions of study are also discussed.

Direct projections from hypothalamic orexin neurons to brainstem cardiac vagal neurons.

PubMed

Dergacheva, Olga; Yamanaka, Akihiro; Schwartz, Alan R; Polotsky, Vsevolod Y; Mendelowitz, David

2016-12-17

Orexin neurons are known to augment the sympathetic control of cardiovascular function, however the role of orexin neurons in parasympathetic cardiac regulation remains unclear. To test the hypothesis that orexin neurons contribute to parasympathetic control we selectively expressed channelrhodopsin-2 (ChR2) in orexin neurons in orexin-Cre transgenic rats and examined postsynaptic currents in cardiac vagal neurons (CVNs) in the dorsal motor nucleus of the vagus (DMV). Simultaneous photostimulation and recording in ChR2-expressing orexin neurons in the lateral hypothalamus resulted in reliable action potential firing as well as large whole-cell currents suggesting a strong expression of ChR2 and reliable optogenetic excitation. Photostimulation of ChR2-expressing fibers in the DMV elicited short-latency (ranging from 3.2ms to 8.5ms) postsynaptic currents in 16 out of 44 CVNs tested. These responses were heterogeneous and included excitatory glutamatergic (63%) and inhibitory GABAergic (37%) postsynaptic currents. The results from this study suggest different sub-population of orexin neurons may exert diverse influences on brainstem CVNs and therefore may play distinct functional roles in parasympathetic control of the heart. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Thermal Expansion "Paradox."

ERIC Educational Resources Information Center

Fakhruddin, Hasan

1993-01-01

Describes a paradox in the equation for thermal expansion. If the calculations for heating a rod and subsequently cooling a rod are determined, the new length of the cool rod is shorter than expected. (PR)

Control of arousal by the orexin neurons

PubMed Central

Alexandre, Chloe; Andermann, Mark L; Scammell, Thomas E

2013-01-01

The orexin-producing neurons in the lateral hypothalamus play an essential role in promoting arousal and maintaining wakefulness. These neurons receive a broad variety of signals related to environmental, physiological and emotional stimuli; they project to almost every brain region involved in the regulation of wakefulness; and they fire most strongly during active wakefulness, high motor activation, and sustained attention. This review focuses on the specific neuronal pathways through which the orexin neurons promote wakefulness and maintain high level of arousal, and how recent studies using optogenetic and pharmacogenetic methods have demonstrated that the locus coeruleus, the tuberomammillary nucleus, and the basal forebrain are some of the key sites mediating the arousing actions of orexins. PMID:23683477

Mechanisms of Gain Control by Voltage-Gated Channels in Intrinsically-Firing Neurons

PubMed Central

Patel, Ameera X.; Burdakov, Denis

2015-01-01

Gain modulation is a key feature of neural information processing, but underlying mechanisms remain unclear. In single neurons, gain can be measured as the slope of the current-frequency (input-output) relationship over any given range of inputs. While much work has focused on the control of basal firing rates and spike rate adaptation, gain control has been relatively unstudied. Of the limited studies on gain control, some have examined the roles of synaptic noise and passive somatic currents, but the roles of voltage-gated channels present ubiquitously in neurons have been less explored. Here, we systematically examined the relationship between gain and voltage-gated ion channels in a conductance-based, tonically-active, model neuron. Changes in expression (conductance density) of voltage-gated channels increased (Ca2+ channel), reduced (K+ channels), or produced little effect (h-type channel) on gain. We found that the gain-controlling ability of channels increased exponentially with the steepness of their activation within the dynamic voltage window (voltage range associated with firing). For depolarization-activated channels, this produced a greater channel current per action potential at higher firing rates. This allowed these channels to modulate gain by contributing to firing preferentially at states of higher excitation. A finer analysis of the current-voltage relationship during tonic firing identified narrow voltage windows at which the gain-modulating channels exerted their effects. As a proof of concept, we show that h-type channels can be tuned to modulate gain by changing the steepness of their activation within the dynamic voltage window. These results show how the impact of an ion channel on gain can be predicted from the relationship between channel kinetics and the membrane potential during firing. This is potentially relevant to understanding input-output scaling in a wide class of neurons found throughout the brain and other nervous systems

Timing paradox of stepping and falls in ageing: not so quick and quick(er) on the trigger

PubMed Central

Mille, Marie‐Laure

2016-01-01

Abstract Physiological and degenerative changes affecting human standing balance are major contributors to falls with ageing. During imbalance, stepping is a powerful protective action for preserving balance that may be voluntarily initiated in recognition of a balance threat, or be induced by an externally imposed mechanical or sensory perturbation. Paradoxically, with ageing and falls, initiation slowing of voluntary stepping is observed together with perturbation‐induced steps that are triggered as fast as or faster than for younger adults. While age‐associated changes in sensorimotor conduction, central neuronal processing and cognitive functions are linked to delayed voluntary stepping, alterations in the coupling of posture and locomotion may also prolong step triggering. It is less clear, however, how these factors may explain the accelerated triggering of induced stepping. We present a conceptual model that addresses this issue. For voluntary stepping, a disruption in the normal coupling between posture and locomotion may underlie step‐triggering delays through suppression of the locomotion network based on an estimation of the evolving mechanical state conditions for stability. During induced stepping, accelerated step initiation may represent an event‐triggering process whereby stepping is released according to the occurrence of a perturbation rather than to the specific sensorimotor information reflecting the evolving instability. In this case, errors in the parametric control of induced stepping and its effectiveness in stabilizing balance would be likely to occur. We further suggest that there is a residual adaptive capacity with ageing that could be exploited to improve paradoxical triggering and other changes in protective stepping to impact fall risk. PMID:26915664

Integrative properties and transfer function of cortical neurons initiating absence seizures in a rat genetic model

PubMed Central

Williams, Mark S.; Altwegg‐Boussac, Tristan; Chavez, Mario; Lecas, Sarah; Mahon, Séverine

2016-01-01

sustained depolarization and an excessive firing rate in between seizures, ictogenic neurons exhibited a pronounced hyperpolarization‐activated depolarization compared to homotypic control neurons. Firing frequency versus injected current relations indicated an increased sensitivity of GAERS cells to weak excitatory inputs, without modifications in the trial‐to‐trial variability of current‐induced firing. During SWDs, the W‐component resulted in paradoxical effects in ictogenic neurons, associating an increased membrane input resistance with a reduction in the current‐evoked firing responses. Conversely, the collapse of cell membrane resistance during the S‐component was accompanied by an elevated current‐evoked firing relative to W‐sequences, which remained, however, lower compared to inter‐ictal periods. These findings show a dynamic modulation of ictogenic neurons’ intrinsic properties that may alter inter‐seizure cortical function and participate in compromising information processing in cortical networks during absences. PMID:27311433

Greenberger-Horne-Zeilinger paradoxes from qudit graph states.

PubMed

Tang, Weidong; Yu, Sixia; Oh, C H

2013-03-08

One fascinating way of revealing quantum nonlocality is the all-versus-nothing test due to Greenberger, Horne, and Zeilinger (GHZ) known as the GHZ paradox. So far genuine multipartite and multilevel GHZ paradoxes are known to exist only in systems containing an odd number of particles. Here we shall construct GHZ paradoxes for an arbitrary number (greater than 3) of particles with the help of qudit graph states on a special kind of graphs, called GHZ graphs. Furthermore, based on the GHZ paradox arising from a GHZ graph, we derive a Bell inequality with two d-outcome observables for each observer, whose maximal violation attained by the corresponding graph state, and a Kochen-Specker inequality testing the quantum contextuality in a state-independent fashion.

Paradox lost. The latah problem revisited.

PubMed

Kenny, M G

1983-03-01

This paper examines the validity of Dr. R. C. Simons' resolution (Simons, R. C. The resolution of the latah paradox. J. Nerv. Ment. Dis., 168: 195-206, 1980) of the so-called latah paradox. Latah, a Malay condition precipitated by sudden fright and involving compulsive obscenity and mimesis, was found to be closely related to local cultural values; yet a paradox seems to arise from the fact that analogous conditions are reported from unrelated cultures. Simons accounts for this by proposing that latah and its kindred states are based on the universal human startle reflex and that latah is merely a culture-specific exploitation of a neurophysiological potential shared by humans and other animals. It is here argued that the evidence does not support such a view and that latah-like conditions are best considered in terms of their local meaning within their societies of origin; ethnographic material from Siberia is examined as a case in point. It is concluded that the "latah paradox" is illusory and that biomedical approaches to the question have seriously misread the nature of the phenomenon and potentially distort clinical practice in relation to it.

Minimum energy control for a two-compartment neuron to extracellular electric fields

NASA Astrophysics Data System (ADS)

Yi, Guo-Sheng; Wang, Jiang; Li, Hui-Yan; Wei, Xi-Le; Deng, Bin

2016-11-01

The energy optimization of extracellular electric field (EF) stimulus for a neuron is considered in this paper. We employ the optimal control theory to design a low energy EF input for a reduced two-compartment model. It works by driving the neuron to closely track a prescriptive spike train. A cost function is introduced to balance the contradictory objectives, i.e., tracking errors and EF stimulus energy. By using the calculus of variations, we transform the minimization of cost function to a six-dimensional two-point boundary value problem (BVP). Through solving the obtained BVP in the cases of three fundamental bifurcations, it is shown that the control method is able to provide an optimal EF stimulus of reduced energy for the neuron to effectively track a prescriptive spike train. Further, the feasibility of the adopted method is interpreted from the point of view of the biophysical basis of spike initiation. These investigations are conducive to designing stimulating dose for extracellular neural stimulation, which are also helpful to interpret the effects of extracellular field on neural activity.

Substance P Differentially Modulates Firing Rate of Solitary Complex (SC) Neurons from Control and Chronic Hypoxia-Adapted Adult Rats

PubMed Central

Nichols, Nicole L.; Powell, Frank L.; Dean, Jay B.; Putnam, Robert W.

2014-01-01

NK1 receptors, which bind substance P, are present in the majority of brainstem regions that contain CO2/H+-sensitive neurons that play a role in central chemosensitivity. However, the effect of substance P on the chemosensitive response of neurons from these regions has not been studied. Hypoxia increases substance P release from peripheral afferents that terminate in the caudal nucleus tractus solitarius (NTS). Here we studied the effect of substance P on the chemosensitive responses of solitary complex (SC: NTS and dorsal motor nucleus) neurons from control and chronic hypoxia-adapted (CHx) adult rats. We simultaneously measured intracellular pH and electrical responses to hypercapnic acidosis in SC neurons from control and CHx adult rats using the blind whole cell patch clamp technique and fluorescence imaging microscopy. Substance P significantly increased the basal firing rate in SC neurons from control and CHx rats, although the increase was smaller in CHx rats. However, substance P did not affect the chemosensitive response of SC neurons from either group of rats. In conclusion, we found that substance P plays a role in modulating the basal firing rate of SC neurons but the magnitude of the effect is smaller for SC neurons from CHx adult rats, implying that NK1 receptors may be down regulated in CHx adult rats. Substance P does not appear to play a role in modulating the firing rate response to hypercapnic acidosis of SC neurons from either control or CHx adult rats. PMID:24516602

Control of arousal by the orexin neurons.

PubMed

Alexandre, Chloe; Andermann, Mark L; Scammell, Thomas E

2013-10-01

The orexin-producing neurons in the lateral hypothalamus play an essential role in promoting arousal and maintaining wakefulness. These neurons receive a broad variety of signals related to environmental, physiological and emotional stimuli; they project to almost every brain region involved in the regulation of wakefulness; and they fire most strongly during active wakefulness, high motor activation, and sustained attention. This review focuses on the specific neuronal pathways through which the orexin neurons promote wakefulness and maintain high level of arousal, and how recent studies using optogenetic and pharmacogenetic methods have demonstrated that the locus coeruleus, the tuberomammillary nucleus, and the basal forebrain are some of the key sites mediating the arousing actions of orexins. Copyright © 2013 Elsevier Ltd. All rights reserved.

Glut2-dependent glucose-sensing controls thermoregulation by enhancing the leptin sensitivity of NPY and POMC neurons.

PubMed

Mounien, Lourdes; Marty, Nell; Tarussio, David; Metref, Salima; Genoux, David; Preitner, Frédéric; Foretz, Marc; Thorens, Bernard

2010-06-01

The physiological contribution of glucose in thermoregulation is not completely established nor whether this control may involve a regulation of the melanocortin pathway. Here, we assessed thermoregulation and leptin sensitivity of hypothalamic arcuate neurons in mice with inactivation of glucose transporter type 2 (Glut2)-dependent glucose sensing. Mice with inactivation of Glut2-dependent glucose sensors are cold intolerant and show increased susceptibility to food deprivation-induced torpor and abnormal hypothermic response to intracerebroventricular administration of 2-deoxy-d-glucose compared to control mice. This is associated with a defect in regulated expression of brown adipose tissue uncoupling protein I and iodothyronine deiodinase II and with a decreased leptin sensitivity of neuropeptide Y (NPY) and proopiomelanocortin (POMC) neurons, as observed during the unfed-to-refed transition or following i.p. leptin injection. Sites of central Glut-2 expression were identified by a genetic tagging approach and revealed that glucose-sensitive neurons were present in the lateral hypothalamus, the dorsal vagal complex, and the basal medulla but not in the arcuate nucleus. NPY and POMC neurons were, however, connected to nerve terminals from Glut2-expressing neurons. Thus, our data suggest that glucose controls thermoregulation and the leptin sensitivity of NPY and POMC neurons through activation of Glut2-dependent glucose-sensing neurons located outside of the arcuate nucleus.

Unveiling consumer's privacy paradox behaviour in an economic exchange.

PubMed

Motiwalla, Luvai F; Li, Xiao-Bai

2016-01-01

Privacy paradox is of great interest to IS researchers and firms gathering personal information. It has been studied from social, behavioural, and economic perspectives independently. However, prior research has not examined the degrees of influence these perspectives contribute to the privacy paradox problem. We combine both economic and behavioural perspectives in our study of the privacy paradox with a price valuation of personal information through an economic experiment combined with a behavioural study on privacy paradox. Our goal is to reveal more insights on the privacy paradox through economic valuation on personal information. Results indicate that general privacy concerns or individual disclosure concerns do not have a significant influence on the price valuation of personal information. Instead, prior disclosure behaviour in specific scenario, like with healthcare providers or social networks, is a better indicator of consumer price valuations.

Moderating attitudes in times of violence through paradoxical thinking intervention.

PubMed

Hameiri, Boaz; Porat, Roni; Bar-Tal, Daniel; Halperin, Eran

2016-10-25

In the current paper, we report a large-scale randomized field experiment, conducted among Jewish Israelis during widespread violence. The study examines the effectiveness of a "real world," multichanneled paradoxical thinking intervention, with messages disseminated through various means of communication (i.e., online, billboards, flyers). Over the course of 6 wk, we targeted a small city in the center of Israel whose population is largely rightwing and religious. Based on the paradoxical thinking principles, the intervention involved transmission of messages that are extreme but congruent with the shared Israeli ethos of conflict. To examine the intervention's effectiveness, we conducted a large-scale field experiment (prepost design) in which we sampled participants from the city population (n = 215) and compared them to a control condition (from different places of residence) with similar demographic and political characteristics (n = 320). Importantly, participants were not aware that the intervention was related to the questionnaires they answered. Results showed that even in the midst of a cycle of ongoing violence within the context of one of the most intractable conflicts in the world, the intervention led hawkish participants to decrease their adherence to conflict-supporting attitudes across time. Furthermore, compared with the control condition, hawkish participants that were exposed to the paradoxical thinking intervention expressed less support for aggressive policies that the government should consider as a result of the escalation in violence and more support for conciliatory policies to end the violence and promote a long-lasting agreement.

Motor neurons in Drosophila flight control: could b1 be the one?

NASA Astrophysics Data System (ADS)

Whitehead, Samuel; Shirangi, Troy; Cohen, Itai

Similar to balancing a stick on one's fingertip, flapping flight is inherently unstable; maintaining stability is a delicate balancing act made possible only by near-constant, often-subtle corrective actions. For fruit flies, such corrective responses need not only be robust, but also fast: the Drosophila flight control reflex has a response latency time of ~5 ms, ranking it among the fastest reflexes in the animal kingdom. How is such rapid, robust control implemented physiologically? Here we present an analysis of a putatively crucial component of the Drosophila flight control circuit: the b1 motor neuron. Specifically, we apply mechanical perturbations to freely-flying Drosophila and analyze the differences in kinematics patterns between flies with manipulated and un-manipulated b1 motor neurons. Ultimately, we hope to identify the functional role of b1 in flight stabilization, with the aim of linking it to previously-proposed, reduced-order models for reflexive control.

Evaluating paradox walnut rootstocks for resistance to Armillaria root disease

USDA-ARS?s Scientific Manuscript database

The most common Juglans regia (English walnut) rootstock in California is Paradox, a hybrid between J. hindsii (Northern California black walnut) and J. regia. Unfortuntely, Paradox rootstock is highly susceptible to Armillaria root disease. The relative resistance of new clonal, Paradox rootstock...

Posttranscriptional control of neuronal development by microRNA networks.

PubMed

Gao, Fen-Biao

2008-01-01

The proper development of the nervous system requires precise spatial and temporal control of gene expression at both the transcriptional and translational levels. In different experimental model systems, microRNAs (miRNAs) - a class of small, endogenous, noncoding RNAs that control the translation and stability of many mRNAs - are emerging as important regulators of various aspects of neuronal development. Further dissection of the in vivo physiological functions of individual miRNAs promises to offer novel mechanistic insights into the gene regulatory networks that ensure the precise assembly of a functional nervous system.

The C. elegans Tailless/TLX transcription factor nhr-67 controls neuronal identity and left/right asymmetric fate diversification.

PubMed

Sarin, Sumeet; Antonio, Celia; Tursun, Baris; Hobert, Oliver

2009-09-01

An understanding of the molecular mechanisms of cell fate determination in the nervous system requires the elucidation of transcriptional regulatory programs that ultimately control neuron-type-specific gene expression profiles. We show here that the C. elegans Tailless/TLX-type, orphan nuclear receptor NHR-67 acts at several distinct steps to determine the identity and subsequent left/right (L/R) asymmetric subtype diversification of a class of gustatory neurons, the ASE neurons. nhr-67 controls several broad aspects of sensory neuron development and, in addition, triggers the expression of a sensory neuron-type-specific selector gene, che-1, which encodes a zinc-finger transcription factor. Subsequent to its induction of overall ASE fate, nhr-67 diversifies the fate of the two ASE neurons ASEL and ASER across the L/R axis by promoting ASER and inhibiting ASEL fate. This function is achieved through direct expression activation by nhr-67 of the Nkx6-type homeobox gene cog-1, an inducer of ASER fate, that is inhibited in ASEL through the miRNA lsy-6. Besides controlling bilateral and asymmetric aspects of ASE development, nhr-67 is also required for many other neurons of diverse lineage history and function to appropriately differentiate, illustrating the broad and diverse use of this type of transcription factor in neuronal development.

Neuronal ensemble control of prosthetic devices by a human with tetraplegia

NASA Astrophysics Data System (ADS)

Hochberg, Leigh R.; Serruya, Mijail D.; Friehs, Gerhard M.; Mukand, Jon A.; Saleh, Maryam; Caplan, Abraham H.; Branner, Almut; Chen, David; Penn, Richard D.; Donoghue, John P.

2006-07-01

Neuromotor prostheses (NMPs) aim to replace or restore lost motor functions in paralysed humans by routeing movement-related signals from the brain, around damaged parts of the nervous system, to external effectors. To translate preclinical results from intact animals to a clinically useful NMP, movement signals must persist in cortex after spinal cord injury and be engaged by movement intent when sensory inputs and limb movement are long absent. Furthermore, NMPs would require that intention-driven neuronal activity be converted into a control signal that enables useful tasks. Here we show initial results for a tetraplegic human (MN) using a pilot NMP. Neuronal ensemble activity recorded through a 96-microelectrode array implanted in primary motor cortex demonstrated that intended hand motion modulates cortical spiking patterns three years after spinal cord injury. Decoders were created, providing a `neural cursor' with which MN opened simulated e-mail and operated devices such as a television, even while conversing. Furthermore, MN used neural control to open and close a prosthetic hand, and perform rudimentary actions with a multi-jointed robotic arm. These early results suggest that NMPs based upon intracortical neuronal ensemble spiking activity could provide a valuable new neurotechnology to restore independence for humans with paralysis.

A Codimension-2 Bifurcation Controlling Endogenous Bursting Activity and Pulse-Triggered Responses of a Neuron Model

PubMed Central

Barnett, William H.; Cymbalyuk, Gennady S.

2014-01-01

The dynamics of individual neurons are crucial for producing functional activity in neuronal networks. An open question is how temporal characteristics can be controlled in bursting activity and in transient neuronal responses to synaptic input. Bifurcation theory provides a framework to discover generic mechanisms addressing this question. We present a family of mechanisms organized around a global codimension-2 bifurcation. The cornerstone bifurcation is located at the intersection of the border between bursting and spiking and the border between bursting and silence. These borders correspond to the blue sky catastrophe bifurcation and the saddle-node bifurcation on an invariant circle (SNIC) curves, respectively. The cornerstone bifurcation satisfies the conditions for both the blue sky catastrophe and SNIC. The burst duration and interburst interval increase as the inverse of the square root of the difference between the corresponding bifurcation parameter and its bifurcation value. For a given set of burst duration and interburst interval, one can find the parameter values supporting these temporal characteristics. The cornerstone bifurcation also determines the responses of silent and spiking neurons. In a silent neuron with parameters close to the SNIC, a pulse of current triggers a single burst. In a spiking neuron with parameters close to the blue sky catastrophe, a pulse of current temporarily silences the neuron. These responses are stereotypical: the durations of the transient intervals–the duration of the burst and the duration of latency to spiking–are governed by the inverse-square-root laws. The mechanisms described here could be used to coordinate neuromuscular control in central pattern generators. As proof of principle, we construct small networks that control metachronal-wave motor pattern exhibited in locomotion. This pattern is determined by the phase relations of bursting neurons in a simple central pattern generator modeled by a chain of

Model-based iterative learning control of Parkinsonian state in thalamic relay neuron

NASA Astrophysics Data System (ADS)

Liu, Chen; Wang, Jiang; Li, Huiyan; Xue, Zhiqin; Deng, Bin; Wei, Xile

2014-09-01

Although the beneficial effects of chronic deep brain stimulation on Parkinson's disease motor symptoms are now largely confirmed, the underlying mechanisms behind deep brain stimulation remain unclear and under debate. Hence, the selection of stimulation parameters is full of challenges. Additionally, due to the complexity of neural system, together with omnipresent noises, the accurate model of thalamic relay neuron is unknown. Thus, the iterative learning control of the thalamic relay neuron's Parkinsonian state based on various variables is presented. Combining the iterative learning control with typical proportional-integral control algorithm, a novel and efficient control strategy is proposed, which does not require any particular knowledge on the detailed physiological characteristics of cortico-basal ganglia-thalamocortical loop and can automatically adjust the stimulation parameters. Simulation results demonstrate the feasibility of the proposed control strategy to restore the fidelity of thalamic relay in the Parkinsonian condition. Furthermore, through changing the important parameter—the maximum ionic conductance densities of low-threshold calcium current, the dominant characteristic of the proposed method which is independent of the accurate model can be further verified.

No information or horizon paradoxes for Th. Smiths

NASA Astrophysics Data System (ADS)

Maes, Christian

2015-10-01

The Statistical mechanician in the street (our Th. Smiths) must be surprised upon hearing popular versions of some of today's most discussed paradoxes in astronomy and cosmology. In fact, rather standard reminders of the meaning of thermal probabilities in statistical mechanics appear to answer the horizon problem (one of the major motivations for inflation theory) and the information paradox (related to black hole physics), at least as they are usually presented. Still the paradoxes point to interesting gaps in our statistical understanding of (quantum) gravitational effects.

Paradoxical response to dexamethasone and spontaneous hypocortisolism in Cushing's disease

PubMed Central

Lila, Anurag R; Sarathi, Vijaya; Bandgar, Tushar R; Shah, Nalini S

2013-01-01

Paradoxical response to dexamethasone and spontaneous development of hypocortisolism are rare features of Cushing's disease. We report a 13-year-old boy with Cushing's disease owing to a pituitary macroadenoma. On initial evaluation, he had partial suppression of serum cortisol by dexamethasone. He developed transient hypocortisolism after first adenomectomy, but the disease recurred after 1 year. Repeat evaluation showed recurrent hypercortisolism and paradoxical response to dexamethasone. He underwent second surgery and, postoperatively, hypercostisolism persisted even after 2 years of surgery. Repeat evaluations after 8 years of second surgery revealed persistent hypocortisolism despite residual tumour of same size and similar plasma adrenocorticotropic hormone (ACTH) levels. We have also shown that the paradoxical increase in serum cortisol was preceded by a paradoxical increase in ACTH. The paradoxical response persisted despite hypocortisolism. This patient with Cushing's disease had two very rare features: paradoxical response to dexamethasone and spontaneous development of hypocortisolism. PMID:23365169

Mechanisms and neuronal networks involved in reactive and proactive cognitive control of interference in working memory.

PubMed

Irlbacher, Kerstin; Kraft, Antje; Kehrer, Stefanie; Brandt, Stephan A

2014-10-01

Cognitive control can be reactive or proactive in nature. Reactive control mechanisms, which support the resolution of interference, start after its onset. Conversely, proactive control involves the anticipation and prevention of interference prior to its occurrence. The interrelation of both types of cognitive control is currently under debate: Are they mediated by different neuronal networks? Or are there neuronal structures that have the potential to act in a proactive as well as in a reactive manner? This review illustrates the way in which integrating knowledge gathered from behavioral studies, functional imaging, and human electroencephalography proves useful in answering these questions. We focus on studies that investigate interference resolution at the level of working memory representations. In summary, different mechanisms are instrumental in supporting reactive and proactive control. Distinct neuronal networks are involved, though some brain regions, especially pre-SMA, possess functions that are relevant to both control modes. Therefore, activation of these brain areas could be observed in reactive, as well as proactive control, but at different times during information processing. Copyright © 2014 Elsevier Ltd. All rights reserved.

Paradoxes of maternal mourning.

PubMed

Brice, C W

1991-02-01

It has been customary to conceptualize mourning as a phasic or stage phenomenon (Lindemann 1944; Parkes 1972; Bowlby 1980; Knapp 1986). Such a conceptualization has proved to be of tremendous didactic value, especially in terms of succinctly organizing and communicating the major affects, behaviors, and reactions of mourning. It is, however, my belief, based upon clinical experience with many forms of bereavement, that the phenomenon of mourning is not comprised of clearly delineated stages and phases. I have come to conceptualize the phenomenon of mourning the death of a loved person as involving the bereaved's struggle with a series of more or less unresolvable paradoxes rather than as a progression through stages that possess relatively distinct and predictable beginning and ending points. The specific paradoxes encountered by a bereaved person differ, of course, in accordance with the relationship that was lost (mother, father, spouse, child, or sibling), the developmental stage of the bereaved (childhood, adolescence, adulthood, or maturity), the type of death (sudden or prolonged), and the cause of death (illness, murder, suicide, or accident). In this paper, I will address those paradoxes that seem specific to maternal mourning - that is, to mothers who are mourning the death of a child.

The myth and reality of Gray's paradox: implication of dolphin drag reduction for technology.

PubMed

Fish, Frank E

2006-06-01

The inconsistency for the calculated high drag on an actively swimming dolphin and underestimated muscle power available resulted in what has been termed Gray's paradox. Although Gray's paradox was flawed, it has been the inspiration for a variety of drag reduction mechanisms. This review examines the present state of knowledge of drag reduction specific to dolphins. Streamlining and special behaviors provide the greatest drag reduction for dolphins. Mechanisms to control flow by maintaining a completely laminar boundary layer over the body have not been demonstrated for dolphins.

The TRH neuron: a hypothalamic integrator of energy metabolism.

PubMed

Lechan, Ronald M; Fekete, Csaba

2006-01-01

Thyrotropin-releasing hormone (TRH) has an important role in the regulation of energy homeostasis not only through effects on thyroid function orchestrated through hypophysiotropic neurons in the hypothalamic paraventricular nucleus (PVN), but also through central effects on feeding behavior, thermogenesis, locomotor activation and autonomic regulation. Hypophysiotropic TRH neurons are located in the medial and periventricular parvocellular subdivisions of the PVN and receive direct monosynaptic projections from two, separate, populations of leptin-responsive neurons in the hypothalamic arcuate nucleus containing either alpha-melanocyte-stimulating hormone (alpha-MSH) and cocaine- and amphetamine-regulated transcript (CART), peptides that promote weight loss and increase energy expenditure, or neuropeptide Y (NPY) and agouti-related protein (AGRP), peptides that promote weight gain and reduce energy expenditure. During fasting, the reduction in TRH mRNA in hypophysiotropic neurons mediated by suppression of alpha-MSH/CART simultaneously with an increase in NPY/AGRP gene expression in arcuate nucleus neurons contributes to the fall in circulating thyroid hormone levels, presumably by increasing the sensitivity of the TRH gene to negative feedback inhibition by thyroid hormone. Endotoxin administration, however, has the paradoxical effect of increasing circulating levels of leptin and melanocortin signaling and CART gene expression in arcuate nucleus neurons, but inhibiting TRH gene expression in hypophysiotropic neurons. This may be explained by an overriding inhibitory effect of endotoxin to increase type 2 iodothyroine deiodinase (D2) in a population of specialized glial cells, tanycytes, located in the base and infralateral walls of the third ventricle. By increasing the conversion of T4 into T3, tanycytes may increase local tissue concenetrations of thyroid hormone, and thereby induce a state of local tissue hyperthyroidism in the region of hypophysisotrophic

A neuronal pathway that controls sperm ejection and storage in female Drosophila.

PubMed

Lee, Kang-Min; Daubnerová, Ivana; Isaac, R Elwyn; Zhang, Chen; Choi, Sekyu; Chung, Jongkyeong; Kim, Young-Joon

2015-03-16

In polyandrous females, sperm storage permits competition between sperm of different mates, and in some species females influence the relative fertilization success of competing sperm in favor of a preferred mate [1, 2]. In female Drosophila melanogaster, sperm competition is strongly influenced by the timing of sperm ejection from the uterus [3, 4]. Understanding how female behavior influences sperm competition requires knowledge of the neuronal mechanisms controlling sperm retention and storage, which is currently lacking. Here, we show that D. melanogaster females eject male ejaculates from the uterus 1-6 hr after mating with a stereotypic behavior regulated by a brain signaling pathway composed of diuretic hormone 44 (Dh44), a neuropeptide related to vertebrate corticotropin-releasing factor (CRF), and its receptor, Dh44R1. Suppression of Dh44 signals in the brain expedites sperm ejection from the uterus, resulting in marked reduction of sperm in the storage organs and decreased fecundity, whereas enhancement of Dh44 signals delays sperm expulsion. The Dh44 function was mapped to six neurons located in the pars intercerebralis of the brain together with a small subset of Dh44R1 neurons that express the sex-specific transcription factor doublesex. This study identifies a neuronal pathway by which females can control sperm retention and storage and provides new insight into how the female might exercise post-copulatory sexual selection. Copyright © 2015 Elsevier Ltd. All rights reserved.

Peripheral Sensory Neurons Expressing Melanopsin Respond to Light

PubMed Central

Matynia, Anna; Nguyen, Eileen; Sun, Xiaoping; Blixt, Frank W.; Parikh, Sachin; Kessler, Jason; Pérez de Sevilla Müller, Luis; Habib, Samer; Kim, Paul; Wang, Zhe Z.; Rodriguez, Allen; Charles, Andrew; Nusinowitz, Steven; Edvinsson, Lars; Barnes, Steven; Brecha, Nicholas C.; Gorin, Michael B.

2016-01-01

The ability of light to cause pain is paradoxical. The retina detects light but is devoid of nociceptors while the trigeminal sensory ganglia (TG) contain nociceptors but not photoreceptors. Melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) are thought to mediate light-induced pain but recent evidence raises the possibility of an alternative light responsive pathway independent of the retina and optic nerve. Here, we show that melanopsin is expressed in both human and mouse TG neurons. In mice, they represent 3% of small TG neurons that are preferentially localized in the ophthalmic branch of the trigeminal nerve and are likely nociceptive C fibers and high-threshold mechanoreceptor Aδ fibers based on a strong size-function association. These isolated neurons respond to blue light stimuli with a delayed onset and sustained firing, similar to the melanopsin-dependent intrinsic photosensitivity observed in ipRGCs. Mice with severe bilateral optic nerve crush exhibit no light-induced responses including behavioral light aversion until treated with nitroglycerin, an inducer of migraine in people and migraine-like symptoms in mice. With nitroglycerin, these same mice with optic nerve crush exhibit significant light aversion. Furthermore, this retained light aversion remains dependent on melanopsin-expressing neurons. Our results demonstrate a novel light-responsive neural function independent of the optic nerve that may originate in the peripheral nervous system to provide the first direct mechanism for an alternative light detection pathway that influences motivated behavior. PMID:27559310

Modeling of inter-neuronal coupling medium and its impact on neuronal synchronization

PubMed Central

Iqbal, Muhammad; Hong, Keum-Shik

2017-01-01

In this paper, modeling of the coupling medium between two neurons, the effects of the model parameters on the synchronization of those neurons, and compensation of coupling strength deficiency in synchronization are studied. Our study exploits the inter-neuronal coupling medium and investigates its intrinsic properties in order to get insight into neuronal-information transmittance and, there from, brain-information processing. A novel electrical model of the coupling medium that represents a well-known RLC circuit attributable to the coupling medium’s intrinsic resistive, inductive, and capacitive properties is derived. Surprisingly, the integration of such properties reveals the existence of a natural three-term control strategy, referred to in the literature as the proportional integral derivative (PID) controller, which can be responsible for synchronization between two neurons. Consequently, brain-information processing can rely on a large number of PID controllers based on the coupling medium properties responsible for the coherent behavior of neurons in a neural network. Herein, the effects of the coupling model (or natural PID controller) parameters are studied and, further, a supervisory mechanism is proposed that follows a learning and adaptation policy based on the particle swarm optimization algorithm for compensation of the coupling strength deficiency. PMID:28486505

The Hydrostatic Paradox.

ERIC Educational Resources Information Center

Wilson, Alpha E.

1995-01-01

Presents an example demonstrating the quantitative resolution of the hydrostatic paradox which is the realization that the force due to fluid pressure on the bottom of a vessel can be considerably greater or considerably less than the weight of the fluid in the vessel. (JRH)

Adaptive, fast walking in a biped robot under neuronal control and learning.

PubMed

Manoonpong, Poramate; Geng, Tao; Kulvicius, Tomas; Porr, Bernd; Wörgötter, Florentin

2007-07-01

Human walking is a dynamic, partly self-stabilizing process relying on the interaction of the biomechanical design with its neuronal control. The coordination of this process is a very difficult problem, and it has been suggested that it involves a hierarchy of levels, where the lower ones, e.g., interactions between muscles and the spinal cord, are largely autonomous, and where higher level control (e.g., cortical) arises only pointwise, as needed. This requires an architecture of several nested, sensori-motor loops where the walking process provides feedback signals to the walker's sensory systems, which can be used to coordinate its movements. To complicate the situation, at a maximal walking speed of more than four leg-lengths per second, the cycle period available to coordinate all these loops is rather short. In this study we present a planar biped robot, which uses the design principle of nested loops to combine the self-stabilizing properties of its biomechanical design with several levels of neuronal control. Specifically, we show how to adapt control by including online learning mechanisms based on simulated synaptic plasticity. This robot can walk with a high speed (>3.0 leg length/s), self-adapting to minor disturbances, and reacting in a robust way to abruptly induced gait changes. At the same time, it can learn walking on different terrains, requiring only few learning experiences. This study shows that the tight coupling of physical with neuronal control, guided by sensory feedback from the walking pattern itself, combined with synaptic learning may be a way forward to better understand and solve coordination problems in other complex motor tasks.

The "Paradox of Interdisciplinarity" in Australian Research Governance

ERIC Educational Resources Information Center

Woelert, Peter; Millar, Victoria

2013-01-01

This paper identifies what can be called the "paradox of interdisciplinarity" (Weingart 2000) in Australian higher education research governance and explores some of its constitutive dimensions. In the Australian context, the paradox of interdisciplinarity primarily concerns the proliferation of a programmatic discourse of…

Moderating attitudes in times of violence through paradoxical thinking intervention

PubMed Central

Hameiri, Boaz; Porat, Roni; Bar-Tal, Daniel; Halperin, Eran

2016-01-01

In the current paper, we report a large-scale randomized field experiment, conducted among Jewish Israelis during widespread violence. The study examines the effectiveness of a “real world,” multichanneled paradoxical thinking intervention, with messages disseminated through various means of communication (i.e., online, billboards, flyers). Over the course of 6 wk, we targeted a small city in the center of Israel whose population is largely rightwing and religious. Based on the paradoxical thinking principles, the intervention involved transmission of messages that are extreme but congruent with the shared Israeli ethos of conflict. To examine the intervention’s effectiveness, we conducted a large-scale field experiment (prepost design) in which we sampled participants from the city population (n = 215) and compared them to a control condition (from different places of residence) with similar demographic and political characteristics (n = 320). Importantly, participants were not aware that the intervention was related to the questionnaires they answered. Results showed that even in the midst of a cycle of ongoing violence within the context of one of the most intractable conflicts in the world, the intervention led hawkish participants to decrease their adherence to conflict-supporting attitudes across time. Furthermore, compared with the control condition, hawkish participants that were exposed to the paradoxical thinking intervention expressed less support for aggressive policies that the government should consider as a result of the escalation in violence and more support for conciliatory policies to end the violence and promote a long-lasting agreement. PMID:27790995

Einstein-Podolsky-Rosen paradox and quantum steering in pulsed optomechanics

NASA Astrophysics Data System (ADS)

He, Q. Y.; Reid, M. D.

2013-11-01

We describe how to generate an Einstein-Podolsky-Rosen (EPR) paradox between a mesoscopic mechanical oscillator and an optical pulse. We find two types of paradox, defined by whether it is the oscillator or the pulse that shows the effect Schrödinger called “steering”. Only the oscillator paradox addresses the question of mesoscopic local reality for a massive system. In that case, EPR's “elements of reality” are defined for the oscillator, and it is these elements of reality that are falsified (if quantum mechanics is complete). For this sort of paradox, we show that a thermal barrier exists, meaning that a threshold level of pulse-oscillator interaction is required for a given thermal occupation n0 of the oscillator. We find there is no equivalent thermal barrier for the entanglement of the pulse with the oscillator or for the EPR paradox that addresses the local reality of the optical system. Finally, we examine the possibility of an EPR paradox between two entangled oscillators. Our work highlights the asymmetrical effect of thermal noise on quantum nonlocality.

Length Paradox in Relativity

ERIC Educational Resources Information Center

Martins, Roberto de A.

1978-01-01

Describes a thought experiment using a general analysis approach with Lorentz transformations to show that the apparent self-contradictions of special relativity concerning the length-paradox are really non-existant. (GA)

Extracellular matrix controls neuronal features that mediate the persistence of fear.

PubMed

Pignataro, Annabella; Pagano, Roberto; Guarneri, Giorgia; Middei, Silvia; Ammassari-Teule, Martine

2017-12-01

Degradation of the chondroitin sulfate proteoglycans of the extracellular matrix (ECM) by injections of the bacterial enzyme chondroitinase ABC (ChABC) in the basolateral amygdala (BLA) does not impair fear memory formation but accelerates its extinction and disrupts its reactivation. These observations suggest that the treatment might selectively interfere with the post-extinction features of neurons that mediate the reinstatement of fear. Here, we report that ChABC mice show regular fear memory and memory-driven c-fos activation and dendritic spine formation in the BLA. These mice then rapidly extinguish their fear response and exhibit a post-extinction concurrent reduction in c-fos activation and large dendritic spines that extends to the anterior cingulate cortex 7 days later. At this remote time point, fear renewal and fear retrieval are impaired. These findings show that a non-cellular component of the brain tissue controls post-extinction levels of neuronal activity and spine enlargement in the regions sequentially remodelled during the formation of recent and remote fear memory. By preventing BLA and aCC neurons to retain neuronal features that serve to reactivate an extinguished fear memory, ECM digestion might offer a therapeutic strategy for durable attenuation of traumatic memories.

Revisiting Hardy's paradox: counterfactual statements, real measurements, entanglement and weak values

NASA Astrophysics Data System (ADS)

Aharonov, Yakir; Botero, Alonso; Popescu, Sandu; Reznik, Benni; Tollaksen, Jeff

2002-08-01

Hardy's paradox is revisited. Usually the paradox is dismissed on grounds of counterfactuality, i.e., because the paradoxical effects appear only when one considers results of experiments which do not actually take place. We suggest a new set of measurements in connection with Hardy's scheme, and show that when they are actually performed, they yield strange and surprising outcomes. More generally, we claim that counterfactual paradoxes point to a deeper structure inherent to quantum mechanics.

A simple explanation of the classic hydrostatic paradox

NASA Astrophysics Data System (ADS)

Kontomaris, Stylianos-Vasileios; Malamou, Anna

2016-07-01

An interesting problem in fluid mechanics, with significant educational importance, is the classic hydrostatic paradox. The hydrostatic paradox states the fact that in different shaped containers, with the same base area, which are filled with a liquid of the same height, the applied force by the liquid on the base of each container is exactly the same. However, if the shape of the container is different, the amount of the liquid (and as a consequence the weight) can greatly vary. In this paper, a simple explanation of the hydrostatic paradox, specifically designed and implemented for educational purposes regarding secondary education, is provided.

Genetic deletion of melanin-concentrating hormone neurons impairs hippocampal short-term synaptic plasticity and hippocampal-dependent forms of short-term memory.

PubMed

Le Barillier, Léa; Léger, Lucienne; Luppi, Pierre-Hervé; Fort, Patrice; Malleret, Gaël; Salin, Paul-Antoine

2015-11-01

The cognitive role of melanin-concentrating hormone (MCH) neurons, a neuronal population located in the mammalian postero-lateral hypothalamus sending projections to all cortical areas, remains poorly understood. Mainly activated during paradoxical sleep (PS), MCH neurons have been implicated in sleep regulation. The genetic deletion of the only known MCH receptor in rodent leads to an impairment of hippocampal dependent forms of memory and to an alteration of hippocampal long-term synaptic plasticity. By using MCH/ataxin3 mice, a genetic model characterized by a selective deletion of MCH neurons in the adult, we investigated the role of MCH neurons in hippocampal synaptic plasticity and hippocampal-dependent forms of memory. MCH/ataxin3 mice exhibited a deficit in the early part of both long-term potentiation and depression in the CA1 area of the hippocampus. Post-tetanic potentiation (PTP) was diminished while synaptic depression induced by repetitive stimulation was enhanced suggesting an alteration of pre-synaptic forms of short-term plasticity in these mice. Behaviorally, MCH/ataxin3 mice spent more time and showed a higher level of hesitation as compared to their controls in performing a short-term memory T-maze task, displayed retardation in acquiring a reference memory task in a Morris water maze, and showed a habituation deficit in an open field task. Deletion of MCH neurons could thus alter spatial short-term memory by impairing short-term plasticity in the hippocampus. Altogether, these findings could provide a cellular mechanism by which PS may facilitate memory encoding. Via MCH neuron activation, PS could prepare the day's learning by increasing and modulating short-term synaptic plasticity in the hippocampus. © 2015 Wiley Periodicals, Inc.

Timing paradox of stepping and falls in ageing: not so quick and quick(er) on the trigger.

PubMed

Rogers, Mark W; Mille, Marie-Laure

2016-08-15

Physiological and degenerative changes affecting human standing balance are major contributors to falls with ageing. During imbalance, stepping is a powerful protective action for preserving balance that may be voluntarily initiated in recognition of a balance threat, or be induced by an externally imposed mechanical or sensory perturbation. Paradoxically, with ageing and falls, initiation slowing of voluntary stepping is observed together with perturbation-induced steps that are triggered as fast as or faster than for younger adults. While age-associated changes in sensorimotor conduction, central neuronal processing and cognitive functions are linked to delayed voluntary stepping, alterations in the coupling of posture and locomotion may also prolong step triggering. It is less clear, however, how these factors may explain the accelerated triggering of induced stepping. We present a conceptual model that addresses this issue. For voluntary stepping, a disruption in the normal coupling between posture and locomotion may underlie step-triggering delays through suppression of the locomotion network based on an estimation of the evolving mechanical state conditions for stability. During induced stepping, accelerated step initiation may represent an event-triggering process whereby stepping is released according to the occurrence of a perturbation rather than to the specific sensorimotor information reflecting the evolving instability. In this case, errors in the parametric control of induced stepping and its effectiveness in stabilizing balance would be likely to occur. We further suggest that there is a residual adaptive capacity with ageing that could be exploited to improve paradoxical triggering and other changes in protective stepping to impact fall risk. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Unveiling consumer’s privacy paradox behaviour in an economic exchange

PubMed Central

Li, Xiao-Bai

2015-01-01

Privacy paradox is of great interest to IS researchers and firms gathering personal information. It has been studied from social, behavioural, and economic perspectives independently. However, prior research has not examined the degrees of influence these perspectives contribute to the privacy paradox problem. We combine both economic and behavioural perspectives in our study of the privacy paradox with a price valuation of personal information through an economic experiment combined with a behavioural study on privacy paradox. Our goal is to reveal more insights on the privacy paradox through economic valuation on personal information. Results indicate that general privacy concerns or individual disclosure concerns do not have a significant influence on the price valuation of personal information. Instead, prior disclosure behaviour in specific scenario, like with healthcare providers or social networks, is a better indicator of consumer price valuations. PMID:27708687

Visualized Characterization for Cerebral Response of Acupuncture Deqi: Paradox Underway

PubMed Central

Yang, Ming-Xiao; Zeng, Fang; Wu, Xi; Chen, Jiao; Liu, Yan-Qin; Feng, Yue; Liang, Fan-Rong

2013-01-01

Acupuncture as an oriental natural healing therapy with prolonged history has been extensively utilized in the management of great numbers of disorders. Deqi, a renowned acupuncture needling sensation, is profoundly regarded as the predictor and also the prerequisite of a preferable acupuncture treatment efficacy. Till now, there is still no consistency being reached towards the mechanism of acupuncture Deqi as a result of the discrepancy for publicly acknowledged evidence. Recent visualized research on Deqi using modern technologies has demonstrated possible central mechanism towards it. However, there is a conspicuous paradox underway in the research of cerebral response to acupuncture Deqi. This paper provided a view of up-to-date studies using visualized tools to characterize the brain response to acupuncture Deqi, such as functional magnetic resonance imaging (fMRI) and positron emission tomography/computed tomography (PET/CT). The paradox was extruded to highlight certain reasons from a TCM view. It is hypothesized that acupoints located at different dermal sites, state of participant, and needling manipulation can all contribute to the current paradox. Hence, further studies on acupuncture Deqi should pay more attention to the strategy of experiment design with generalized measurement, valid sham control methods, and more to subjects in diseased condition. PMID:23935686

Control of neuronal morphology and connectivity: emerging developmental roles for gap junctional proteins.

PubMed

Baker, Michael W; Macagno, Eduardo R

2014-04-17

Recent evidence indicates that gap junction (GJ) proteins can play a critical role in controlling neuronal connectivity as well as cell morphology in the developing nervous system. GJ proteins may function analogously to cell adhesion molecules, mediating cellular recognition and selective neurite adhesion. Moreover, during synaptogenesis electrical synapses often herald the later establishment of chemical synapses, and thus may help facilitate activity-dependent sculpting of synaptic terminals. Recent findings suggest that the morphology and connectivity of embryonic leech neurons are fundamentally organized by the type and perhaps location of the GJ proteins they express. For example, ectopic expression in embryonic leech neurons of certain innexins that define small GJ-linked networks of cells leads to the novel coupling of the expressing cell into that network. Moreover, gap junctions appear to mediate interactions among homologous neurons that modulate process outgrowth and stability. We propose that the selective formation of GJs between developing neurons and perhaps glial cells in the CNS helps orchestrate not only cellular synaptic connectivity but also can have a pronounced effect on the arborization and morphology of those cells involved. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Implementing Parrondo’s paradox with two-coin quantum walks

PubMed Central

Rajendran, Jishnu

2018-01-01

Parrondo’s paradox is ubiquitous in games, ratchets and random walks. The apparent paradox, devised by J. M. R. Parrondo, that two losing games A and B can produce a winning outcome has been adapted in many physical and biological systems to explain their working. However, proposals on demonstrating Parrondo’s paradox using quantum walks failed for a large number of steps. In this work, we show that instead of a single coin if we consider a two-coin initial state which may or may not be entangled, we can observe a genuine Parrondo’s paradox with quantum walks. Furthermore, we focus on reasons for this and pin down the asymmetry in initial two-coin state or asymmetry in shift operator, either of which is necessary for observing a genuine Parrondo’s paradox. We extend our work to a three-coin initial state too with similar results. The implications of our work for observing quantum ratchet-like behaviour using quantum walks are also discussed. PMID:29515873

The effect of yoga on puborectalis paradox.

PubMed

Dolk, A; Holmström, B; Johansson, C; Frostell, C; Nilsson, B Y

1991-08-01

Nine patients with severe defaecation difficulties primarily considered to be due to puborectalis dysfunction (puborectalis paradox), verified by electromyography (EMG) of the striated anal sphincter muscles, were offered training in Yogic techniques of relaxation and muscle control in order to change the activity of the pelvic floor muscles during attempted defaecation. Five patients completed the training program of 20 2-hour sessions and were re-examined clinically and with EMG. One patient regained a normal EMG pattern but none of the patients improved clinically.

Crystalline lens paradoxes revisited: significance of age-related restructuring of the GRIN.

PubMed

Sheil, Conor J; Goncharov, Alexander V

2017-09-01

The accommodating volume-constant age-dependent optical (AVOCADO) model of the crystalline lens is used to explore the age-related changes in ocular power and spherical aberration. The additional parameter m in the GRIN lens model allows decoupling of the axial and radial GRIN profiles, and is used to stabilise the age-related change in ocular power. Data for age-related changes in ocular geometry and lens parameter P in the axial GRIN profile were taken from published experimental data. In our age-dependent eye model, the ocular refractive power shows behaviour similar to the previously unexplained "lens paradox". Furthermore, ocular spherical aberration agrees with the data average, in contrast to the proposed "spherical aberration paradox". The additional flexibility afforded by parameter m , which controls the ratio of the axial and radial GRIN profile exponents, has allowed us to study the restructuring of the lens GRIN medium with age, resulting in a new interpretation of the origin of the power and spherical aberration paradoxes. Our findings also contradict the conceptual idea that the ageing eye is similar to the accommodating eye.

Cardiac neuronal hierarchy in health and disease.

PubMed

Armour, J Andrew

2004-08-01

The cardiac neuronal hierarchy can be represented as a redundant control system made up of spatially distributed cell stations comprising afferent, efferent, and interconnecting neurons. Its peripheral and central neurons are in constant communication with one another such that, for the most part, it behaves as a stochastic control system. Neurons distributed throughout this hierarchy interconnect via specific linkages such that each neuronal cell station is involved in temporally dependent cardio-cardiac reflexes that control overlapping, spatially organized cardiac regions. Its function depends primarily, but not exclusively, on inputs arising from afferent neurons transducing the cardiovascular milieu to directly or indirectly (via interconnecting neurons) modify cardiac motor neurons coordinating regional cardiac behavior. As the function of the whole is greater than that of its individual parts, stable cardiac control occurs most of the time in the absence of direct cause and effect. During altered cardiac status, its redundancy normally represents a stabilizing feature. However, in the presence of regional myocardial ischemia, components within the intrinsic cardiac nervous system undergo pathological change. That, along with any consequent remodeling of the cardiac neuronal hierarchy, alters its spatially and temporally organized reflexes such that populations of neurons, acting in isolation, may destabilize efferent neuronal control of regional cardiac electrical and/or mechanical events.

Unkempt is negatively regulated by mTOR and uncouples neuronal differentiation from growth control.

PubMed

Avet-Rochex, Amélie; Carvajal, Nancy; Christoforou, Christina P; Yeung, Kelvin; Maierbrugger, Katja T; Hobbs, Carl; Lalli, Giovanna; Cagin, Umut; Plachot, Cedric; McNeill, Helen; Bateman, Joseph M

2014-09-01

Neuronal differentiation is exquisitely controlled both spatially and temporally during nervous system development. Defects in the spatiotemporal control of neurogenesis cause incorrect formation of neural networks and lead to neurological disorders such as epilepsy and autism. The mTOR kinase integrates signals from mitogens, nutrients and energy levels to regulate growth, autophagy and metabolism. We previously identified the insulin receptor (InR)/mTOR pathway as a critical regulator of the timing of neuronal differentiation in the Drosophila melanogaster eye. Subsequently, this pathway has been shown to play a conserved role in regulating neurogenesis in vertebrates. However, the factors that mediate the neurogenic role of this pathway are completely unknown. To identify downstream effectors of the InR/mTOR pathway we screened transcriptional targets of mTOR for neuronal differentiation phenotypes in photoreceptor neurons. We identified the conserved gene unkempt (unk), which encodes a zinc finger/RING domain containing protein, as a negative regulator of the timing of photoreceptor differentiation. Loss of unk phenocopies InR/mTOR pathway activation and unk acts downstream of this pathway to regulate neurogenesis. In contrast to InR/mTOR signalling, unk does not regulate growth. unk therefore uncouples the role of the InR/mTOR pathway in neurogenesis from its role in growth control. We also identified the gene headcase (hdc) as a second downstream regulator of the InR/mTOR pathway controlling the timing of neurogenesis. Unk forms a complex with Hdc, and Hdc expression is regulated by unk and InR/mTOR signalling. Co-overexpression of unk and hdc completely suppresses the precocious neuronal differentiation phenotype caused by loss of Tsc1. Thus, Unk and Hdc are the first neurogenic components of the InR/mTOR pathway to be identified. Finally, we show that Unkempt-like is expressed in the developing mouse retina and in neural stem/progenitor cells, suggesting

Prenatal programming by testosterone of hypothalamic metabolic control neurones in the ewe.

PubMed

Sheppard, K M; Padmanabhan, V; Coolen, L M; Lehman, M N

2011-05-01

Ewes treated prenatally with testosterone develop metabolic deficits, including insulin resistance, in addition to reproductive dysfunctions that collectively mimic polycystic ovarian syndrome (PCOS), a common endocrine disease in women. We hypothesised that metabolic deficits associated with prenatal testosterone excess involve alterations in arcuate nucleus (ARC) neurones that contain either agouti-related peptide (AgRP) or pro-opiomelanocortin (POMC). Characterisation of these neurones in the ewe showed that immunoreactive AgRP and POMC neurones were present in separate populations in the ARC, that AgRP and POMC neurones co-expressed either neuropeptide Y or cocaine- and amphetamine-regulated transcript, respectively, and that each population had a high degree of co-localisation with androgen receptors. Examination of the effect of prenatal testosterone exposure on the number of AgRP and POMC neurones in adult ewes showed that prenatal testosterone excess significantly increased the number of AgRP but not POMC neurones compared to controls; this increase was restricted to the middle division of the ARC, was mimicked by prenatal treatment with dihydrotestosterone, a non-aromatisable androgen, and was blocked by co-treatment of prenatal testosterone with the anti-androgen, flutamide. The density of AgRP fibre immunoreactivity in the preoptic area, paraventricular nucleus, lateral hypothalamus and dorsomedial hypothalamic nucleus was also increased by prenatal testosterone exposure. Thus, ewes that were exposed to androgens during foetal life showed alterations in the number of AgRP-immunoreactive neurones and the density of fibre immunoreactivity in their projection areas, suggestive of permanent prenatal programming of metabolic circuitry that may, in turn, contribute to insulin resistance and an increased risk of obesity in this model of PCOS. © 2011 The Authors. Journal of Neuroendocrinology © 2011 Blackwell Publishing Ltd.

Submillisecond Optogenetic Control of Neuronal Firing with Two-Photon Holographic Photoactivation of Chronos

PubMed Central

Ronzitti, Emiliano; Conti, Rossella; Zampini, Valeria; Tanese, Dimitrii; Klapoetke, Nathan; Boyden, Edward S.; Papagiakoumou, Eirini

2017-01-01

Optogenetic neuronal network manipulation promises to unravel a long-standing mystery in neuroscience: how does microcircuit activity relate causally to behavioral and pathological states? The challenge to evoke spikes with high spatial and temporal complexity necessitates further joint development of light-delivery approaches and custom opsins. Two-photon (2P) light-targeting strategies demonstrated in-depth generation of action potentials in photosensitive neurons both in vitro and in vivo, but thus far lack the temporal precision necessary to induce precisely timed spiking events. Here, we show that efficient current integration enabled by 2P holographic amplified laser illumination of Chronos, a highly light-sensitive and fast opsin, can evoke spikes with submillisecond precision and repeated firing up to 100 Hz in brain slices from Swiss male mice. These results pave the way for optogenetic manipulation with the spatial and temporal sophistication necessary to mimic natural microcircuit activity. SIGNIFICANCE STATEMENT To reveal causal links between neuronal activity and behavior, it is necessary to develop experimental strategies to induce spatially and temporally sophisticated perturbation of network microcircuits. Two-photon computer generated holography (2P-CGH) recently demonstrated 3D optogenetic control of selected pools of neurons with single-cell accuracy in depth in the brain. Here, we show that exciting the fast opsin Chronos with amplified laser 2P-CGH enables cellular-resolution targeting with unprecedented temporal control, driving spiking up to 100 Hz with submillisecond onset precision using low laser power densities. This system achieves a unique combination of spatial flexibility and temporal precision needed to pattern optogenetically inputs that mimic natural neuronal network activity patterns. PMID:28972125

Munc13 controls the location and efficiency of dense-core vesicle release in neurons.

PubMed

van de Bospoort, Rhea; Farina, Margherita; Schmitz, Sabine K; de Jong, Arthur; de Wit, Heidi; Verhage, Matthijs; Toonen, Ruud F

2012-12-10

Neuronal dense-core vesicles (DCVs) contain diverse cargo crucial for brain development and function, but the mechanisms that control their release are largely unknown. We quantified activity-dependent DCV release in hippocampal neurons at single vesicle resolution. DCVs fused preferentially at synaptic terminals. DCVs also fused at extrasynaptic sites but only after prolonged stimulation. In munc13-1/2-null mutant neurons, synaptic DCV release was reduced but not abolished, and synaptic preference was lost. The remaining fusion required prolonged stimulation, similar to extrasynaptic fusion in wild-type neurons. Conversely, Munc13-1 overexpression (M13OE) promoted extrasynaptic DCV release, also without prolonged stimulation. Thus, Munc13-1/2 facilitate DCV fusion but, unlike for synaptic vesicles, are not essential for DCV release, and M13OE is sufficient to produce efficient DCV release extrasynaptically.

Patent foramen ovale and paradoxical embolization: a historical perspective.

PubMed

Lippmann, H; Rafferty, T

1993-01-01

The use of transesophageal echocardiography for intraoperative management of critically ill patients allows for routine evaluation of foramen ovale patency. The high prevalence of preoperatively unrecognized flow-patency of this structure has led investigators to emphasize the potential for paradoxical embolization in any patient undergoing anesthesia. This perspective led us to research earliest documentation of paradoxical embolization through a patent foramen ovale as a historical issue with present day relevance. This report examines the 1877 text of Julius Cohnheim in which he described a fatal case of paradoxical embolization to the middle meningeal artery. The 1880 manuscript of Moritz Litten documenting paradoxical embolization to the lower extremity is also presented. Both translations, to our knowledge, represent the first such representations of both the original 1877 edition of Cohnheim's work and Litten's journal article.

A Resolution of the Paradox of Enrichment

NASA Astrophysics Data System (ADS)

Feng, Z. C.; Li, Y. Charles

2015-06-01

The paradox of enrichment was observed by Rosenzweig [1971] in a class of predator-prey models. Two of the parameters in the models are crucial for the paradox. These two parameters are the prey's carrying capacity and prey's half-saturation for predation. Intuitively, increasing the carrying capacity due to enrichment of the prey's environment should lead to a more stable predator-prey system. Analytically, it turns out that increasing the carrying capacity always leads to an unstable predator-prey system that is susceptible to extinction from environmental random perturbations. This is the so-called paradox of enrichment. Our resolution here rests upon a closer investigation on a dimensionless number H formed from the carrying capacity and the prey's half-saturation. By recasting the models into dimensionless forms, the models are in fact governed by a few dimensionless numbers including H. The effects of the two parameters: carrying capacity and half-saturation are incorporated into the number H. In fact, increasing the carrying capacity is equivalent (i.e. has the same effect on H) to decreasing the half-saturation which implies more aggressive predation. Since there is no paradox between more aggressive predation and instability of the predator-prey system, the paradox of enrichment is resolved. The so-called instability of the predator-prey system is characterized by the existence of a stable limit cycle in the phase plane, which gets closer and closer to the predator axis and prey axis. Due to random environmental perturbations, this can lead to extinction. We also further explore spatially dependent models for which the phase space is infinite-dimensional. The spatially independent limit cycle which is generated by a Hopf bifurcation from an unstable steady state, is linearly stable in the infinite-dimensional phase space. Numerical simulations indicate that the basin of attraction of the limit cycle is riddled. This shows that spatial perturbations can

Different modes of APC/C activation control growth and neuron-glia interaction in the developing Drosophila eye.

PubMed

Neuert, Helen; Yuva-Aydemir, Yeliz; Silies, Marion; Klämbt, Christian

2017-12-15

The development of the nervous system requires tight control of cell division, fate specification and migration. The anaphase-promoting complex/cyclosome (APC/C) is an E3 ubiquitin ligase that affects different steps of cell cycle progression, as well as having postmitotic functions in nervous system development. It can therefore link different developmental stages in one tissue. The two adaptor proteins, Fizzy/Cdc20 and Fizzy-related/Cdh1, confer APC/C substrate specificity. Here, we show that two distinct modes of APC/C function act during Drosophila eye development. Fizzy/Cdc20 controls the early growth of the eye disc anlage and the concomitant entry of glial cells onto the disc. In contrast, fzr/cdh1 acts during neuronal patterning and photoreceptor axon growth, and subsequently affects neuron-glia interaction. To further address the postmitotic role of Fzr/Cdh1 in controlling neuron-glia interaction, we identified a series of novel APC/C candidate substrates. Four of our candidate genes are required for fzr/cdh1 -dependent neuron-glia interaction, including the dynein light chain Dlc90F Taken together, our data show how different modes of APC/C activation can couple early growth and neuron-glia interaction during eye disc development. © 2017. Published by The Company of Biologists Ltd.

Paradox Lost? No, Paradox Found! Reply to Tomasello and Akhtar (2003).

ERIC Educational Resources Information Center

Naigles, Letitia R.

2003-01-01

Asserts that the posited paradox between infancy and toddlerhood language was not eliminated by Tomasello and Akhtar's appeal to infants' robust statistical learning abilities. Maintains that scrutiny of their studies supports the resolution that abstracting linguistic form is easy for infants and that toddlers find it difficult to integrate…

Paradoxical reaction to antituberculosis therapy in a patient with lupus vulgaris.

PubMed

Santesteban, R; Bonaut, B; Córdoba, A; Yanguas, I

2015-03-01

Patients receiving treatment for tuberculosis may experience an unexpected deterioration of their disease; this is known as a paradoxical reaction. We present the case of a 59-year-old man with lupus vulgaris who experienced a paradoxical deterioration of cutaneous lesions after starting antituberculosis therapy. The reaction was self-limiting; the lesions gradually improved, and the final outcome was very good. Paradoxical reactions are well-known in patients with human immunodeficiency virus (HIV) infection who start antiretroviral therapy, but they can also occur in non-HIV-infected patients with tuberculosis who start antituberculosis therapy. In the literature reviewed, paradoxical reactions involving skin lesions were described in patients with miliary tuberculosis. The case we report is the first of a paradoxical reaction in lupus vulgaris. The increasing frequency of tuberculosis in Spain could lead to a rise in the number of paradoxical reactions. Copyright © 2014 Elsevier España, S.L.U. y AEDV. All rights reserved.

Spin entanglement, decoherence and Bohm's EPR paradox.

PubMed

Cavalcanti, E G; Drummond, P D; Bachor, H A; Reid, M D

2009-10-12

We obtain criteria for entanglement and the EPR paradox for spin-entangled particles and analyse the effects of decoherence caused by absorption and state purity errors. For a two qubit photonic state, entanglement can occur for all transmission efficiencies. In this case, the state preparation purity must be above a threshold value. However, Bohm's spin EPR paradox can be achieved only above a critical level of loss. We calculate a required efficiency of 58%, which appears achievable with current quantum optical technologies. For a macroscopic number of particles prepared in a correlated state, spin entanglement and the EPR paradox can be demonstrated using our criteria for efficiencies eta > 1/3 and eta > 2/3 respectively. This indicates a surprising insensitivity to loss decoherence, in a macroscopic system of ultra-cold atoms or photons.

A quantum Rosetta Stone for the information paradox

NASA Astrophysics Data System (ADS)

Pando Zayas, Leopoldo A.

2014-11-01

The black hole information loss paradox epitomizes the contradictions between general relativity and quantum field theory. The AdS/conformal field theory (CFT) correspondence provides an implicit answer for the information loss paradox in black hole physics by equating a gravity theory with an explicitly unitary field theory. Gravitational collapse in asymptotically AdS spacetimes is generically turbulent. Given that the mechanism to read out the information about correlations functions in the field theory side is plagued by deterministic classical chaos, we argue that quantum chaos might provide the true Rosetta Stone for answering the information paradox in the context of the AdS/CFT correspondence.

Paradox and Double Binds in Adventure-Based Education.

ERIC Educational Resources Information Center

Bacon, Stephen Barcia

Paradox and therapeutic double bind techniques are used to overcome resistance in students with a history of success avoidance. Predictions of failure, restraining comments, and the use of paradox in the midst of an activity are defended theoretically by presenting historical roots and a rationale of effectiveness. A skill-building approach…

Paradox of pattern separation and adult neurogenesis: A dual role for new neurons balancing memory resolution and robustness.

PubMed

Johnston, Stephen T; Shtrahman, Matthew; Parylak, Sarah; Gonçalves, J Tiago; Gage, Fred H

2016-03-01

Hippocampal adult neurogenesis is thought to subserve pattern separation, the process by which similar patterns of neuronal inputs are transformed into distinct neuronal representations, permitting the discrimination of highly similar stimuli in hippocampus-dependent tasks. However, the mechanism by which immature adult-born dentate granule neurons cells (abDGCs) perform this function remains unknown. Two theories of abDGC function, one by which abDGCs modulate and sparsify activity in the dentate gyrus and one by which abDGCs act as autonomous coding units, are generally suggested to be mutually exclusive. This review suggests that these two mechanisms work in tandem to dynamically regulate memory resolution while avoiding memory interference and maintaining memory robustness. Copyright © 2015 Elsevier Inc. All rights reserved.

Reframing the meaning of disability to families: the embrace of paradox.

PubMed

Larson, E

1998-10-01

In our society, families turn to medical science and health practitioners for assistance when a family member becomes disabled. In the cases of chronic illnesses and developmental disabilities, health professionals may focus interventions on the disease processes, feeling unprepared to deal with the broader issues families struggle with in managing disability. In addition, collaboration between professionals and parents may be strained when family's discourse is viewed as unrealistic, overly emotional, exceedingly optimistic and confusing by professionals. Using in-depth case studies, this qualitative research examined the daily occupations and subjective well-being of six Mexican-origin mothers parenting children with disabilities. Emergent findings demonstrated that these mothers do express apparently contradictory emotions of grief and joy, hope and fear that influenced their subjective well-being. The meaning of the mothers' contrary statements was illuminated in a life metaphor, the embrace of paradox. The embrace of paradox was the management of the internal tension of opposing forces between loving the child as he or she was and wanting to erase the disability, between dealing with the incurability while pursuing solutions and between maintaining hopefulness for the child's future while being given negative information and battling their own fears. The tensions created by the paradox promoted an internal striving to maintain a tenuous hopefulness despite "crashes" in their maternal work, and promoted an extension of maternal skills working toward a hopeful life trajectory for the mother and her child. In the embrace of paradox mothers created a positive bias and regained a sense of control that fueled their optimism in maternal work.

The Neuronal Control of Flying Prey Interception in Dragonflies

DTIC Science & Technology

2014-08-19

Gonzalez-Bellido’s fluorescent dye ( Lucifer -yellow) injections illuminated for the first time the anatomy of the output regions of the TSDNs...out in Cape Cod (MA) to test the effect of bead size(C), and in the Olberg Laboratory (Union College, NY) to test the effect of bead speed by...AFRL-OSR-VA-TR-2014-0193 THE NEURONAL CONTROL OF FLYING PREY INTERCEPTION IN DRAGONFLIES Robert Olberg TRUSTEES OF UNION COLLEGE IN THE TOWN OF

Neuronal control of locomotor handedness in Drosophila.

PubMed

Buchanan, Sean M; Kain, Jamey S; de Bivort, Benjamin L

2015-05-26

Genetically identical individuals display variability in their physiology, morphology, and behaviors, even when reared in essentially identical environments, but there is little mechanistic understanding of the basis of such variation. Here, we investigated whether Drosophila melanogaster displays individual-to-individual variation in locomotor behaviors. We developed a new high-throughout platform capable of measuring the exploratory behavior of hundreds of individual flies simultaneously. With this approach, we find that, during exploratory walking, individual flies exhibit significant bias in their left vs. right locomotor choices, with some flies being strongly left biased or right biased. This idiosyncrasy was present in all genotypes examined, including wild-derived populations and inbred isogenic laboratory strains. The biases of individual flies persist for their lifetime and are nonheritable: i.e., mating two left-biased individuals does not yield left-biased progeny. This locomotor handedness is uncorrelated with other asymmetries, such as the handedness of gut twisting, leg-length asymmetry, and wing-folding preference. Using transgenics and mutants, we find that the magnitude of locomotor handedness is under the control of columnar neurons within the central complex, a brain region implicated in motor planning and execution. When these neurons are silenced, exploratory laterality increases, with more extreme leftiness and rightiness. This observation intriguingly implies that the brain may be able to dynamically regulate behavioral individuality.

Motor control may support mirror neuron research with new hypotheses and methods. Reply to comments on "Grasping synergies: A motor-control approach to the mirror neuron mechanism"

NASA Astrophysics Data System (ADS)

D'Ausilio, Alessandro; Bartoli, Eleonora; Maffongelli, Laura

2015-03-01

We are grateful to all commentators for their insightful commentaries and observations that enrich our proposal. One of our aims was indeed to bridge the gap between fields of research that, progressing independently, are facing similar issues regarding the neural representation of motor knowledge. In this respect, we were pleased to receive feedback from eminent researchers on both the mirror neuron as well as the motor control fields. Their expertise covers animal and human neurophysiology, as well as the computational modeling of neural and behavioral processes. Given their heterogeneous cultural perspectives and research approaches, a number of important open questions were raised. For simplicity we separated these issues into four sections. In the first section we present methodological aspects regarding how synergies can be measured in paradigms investigating the human mirror system. The second section regards the fundamental definition of what exactly synergies might be. The third concerns how synergies can generate testable predictions in mirror neuron research. Finally, the fourth section deals with the ultimate question regarding the function of the mirror neuron system.

Cholinergic Neurons Excite Cortically Projecting Basal Forebrain GABAergic Neurons

PubMed Central

Yang, Chun; McKenna, James T.; Zant, Janneke C.; Winston, Stuart; Basheer, Radhika

2014-01-01

The basal forebrain (BF) plays an important role in the control of cortical activation and attention. Understanding the modulation of BF neuronal activity is a prerequisite to treat disorders of cortical activation involving BF dysfunction, such as Alzheimer's disease. Here we reveal the interaction between cholinergic neurons and cortically projecting BF GABAergic neurons using immunohistochemistry and whole-cell recordings in vitro. In GAD67-GFP knock-in mice, BF cholinergic (choline acetyltransferase-positive) neurons were intermingled with GABAergic (GFP+) neurons. Immunohistochemistry for the vesicular acetylcholine transporter showed that cholinergic fibers apposed putative cortically projecting GABAergic neurons containing parvalbumin (PV). In coronal BF slices from GAD67-GFP knock-in or PV-tdTomato mice, pharmacological activation of cholinergic receptors with bath application of carbachol increased the firing rate of large (>20 μm diameter) BF GFP+ and PV (tdTomato+) neurons, which exhibited the intrinsic membrane properties of cortically projecting neurons. The excitatory effect of carbachol was blocked by antagonists of M1 and M3 muscarinic receptors in two subpopulations of BF GABAergic neurons [large hyperpolarization-activated cation current (Ih) and small Ih, respectively]. Ion substitution experiments and reversal potential measurements suggested that the carbachol-induced inward current was mediated mainly by sodium-permeable cation channels. Carbachol also increased the frequency of spontaneous excitatory and inhibitory synaptic currents. Furthermore, optogenetic stimulation of cholinergic neurons/fibers caused a mecamylamine- and atropine-sensitive inward current in putative GABAergic neurons. Thus, cortically projecting, BF GABAergic/PV neurons are excited by neighboring BF and/or brainstem cholinergic neurons. Loss of cholinergic neurons in Alzheimer's disease may impair cortical activation, in part, through disfacilitation of BF cortically

Scalable control of mounting and attack by Esr1+ neurons in the ventromedial hypothalamus.

PubMed

Lee, Hyosang; Kim, Dong-Wook; Remedios, Ryan; Anthony, Todd E; Chang, Angela; Madisen, Linda; Zeng, Hongkui; Anderson, David J

2014-05-29

Social behaviours, such as aggression or mating, proceed through a series of appetitive and consummatory phases that are associated with increasing levels of arousal. How such escalation is encoded in the brain, and linked to behavioural action selection, remains an unsolved problem in neuroscience. The ventrolateral subdivision of the murine ventromedial hypothalamus (VMHvl) contains neurons whose activity increases during male-male and male-female social encounters. Non-cell-type-specific optogenetic activation of this region elicited attack behaviour, but not mounting. We have identified a subset of VMHvl neurons marked by the oestrogen receptor 1 (Esr1), and investigated their role in male social behaviour. Optogenetic manipulations indicated that Esr1(+) (but not Esr1(-)) neurons are sufficient to initiate attack, and that their activity is continuously required during ongoing agonistic behaviour. Surprisingly, weaker optogenetic activation of these neurons promoted mounting behaviour, rather than attack, towards both males and females, as well as sniffing and close investigation. Increasing photostimulation intensity could promote a transition from close investigation and mounting to attack, within a single social encounter. Importantly, time-resolved optogenetic inhibition experiments revealed requirements for Esr1(+) neurons in both the appetitive (investigative) and the consummatory phases of social interactions. Combined optogenetic activation and calcium imaging experiments in vitro, as well as c-Fos analysis in vivo, indicated that increasing photostimulation intensity increases both the number of active neurons and the average level of activity per neuron. These data suggest that Esr1(+) neurons in VMHvl control the progression of a social encounter from its appetitive through its consummatory phases, in a scalable manner that reflects the number or type of active neurons in the population.

Deep brain stimulation of the inferior colliculus: a possible animal model to study paradoxical kinesia observed in some parkinsonian patients?

PubMed

Melo-Thomas, Liana; Thomas, Uwe

2015-02-15

The inferior colliculus (IC) plays an important role in the normal processing of the acoustic message and is also involved in the filtering of acoustic stimuli of aversive nature. The neural substrate of the IC can also influence haloperidol-induced catalepsy. Considering that (i) paradoxical kinesia, observed in some parkinsonian patients, seems to be dependent of their emotional state and (ii) deep brain stimulation (DBS) represents an alternative therapeutic route for the relief of parkinsonian symptoms, the present study investigated the consequence of DBS at the IC on the catalepsy induced by haloperidol in rats. Additionally, we investigated if DBS of the IC can elicit motor responses in anesthetized rats and whether DBS elicits distinct neural firing patterns of activity at the dorsal cortex (DCIC) or central nucleus (CNIC) of the IC. A significant reduction of the catalepsy response was seen in rats previously given haloperidol and receiving DBS at the IC. In addition, electrical stimulation to the ventral part of the CNIC induced immediate motor responses in anesthetized rats. The neuronal spontaneous activity was higher at the ventral part of the CNIC than the dorsal part. DBS to the ventral part but not to the dorsal part of the CNIC increased the spike rate at neurons a few hundred microns away from the stimulation site. It is possible that the IC plays a role in the sensorimotor gating activated by emotional stimuli, and that DBS at the IC can be a promising new animal model to study paradoxical kinesia in rats. Copyright © 2014 Elsevier B.V. All rights reserved.

Control of alternative splicing by forskolin through hnRNP K during neuronal differentiation.

PubMed

Cao, Wenguang; Razanau, Aleh; Feng, Dairong; Lobo, Vincent G; Xie, Jiuyong

2012-09-01

The molecular basis of cell signal-regulated alternative splicing at the 3' splice site remains largely unknown. We isolated a protein kinase A-responsive ribonucleic acid (RNA) element from a 3' splice site of the synaptosomal-associated protein 25 (Snap25) gene for forskolin-inhibited splicing during neuronal differentiation of rat pheochromocytoma PC12 cells. The element binds specifically to heterogeneous nuclear ribonucleo protein (hnRNP) K in a phosphatase-sensitive way, which directly competes with the U2 auxiliary factor U2AF65, an essential component of early spliceosomes. Transcripts with similarly localized hnRNP K target motifs upstream of alternative exons are enriched in genes often associated with neurological diseases. We show that such motifs upstream of the Runx1 exon 6 also bind hnRNP K, and importantly, hnRNP K is required for forskolin-induced repression of the exon. Interestingly, this exon encodes the peptide domain that determines the switch of the transcriptional repressor/activator activity of Runx1, a change known to be critical in specifying neuron lineages. Consistent with an important role of the target genes in neurons, knocking down hnRNP K severely disrupts forskolin-induced neurite growth. Thus, through hnRNP K, the neuronal differentiation stimulus forskolin targets a critical 3' splice site component of the splicing machinery to control alternative splicing of crucial genes. This also provides a regulated direct competitor of U2AF65 for cell signal control of 3' splice site usage.

Patent Foramen Ovale: Is Stroke Due to Paradoxical Embolism?

NASA Technical Reports Server (NTRS)

Ranoux, D.; Cohen, A.; Cabanes, L.; Amarenco, P.; Bousser, M. G.; Mas, J. L.

1993-01-01

Background and Purpose: A patent foramen ovale has been reported to be significantly more frequent in young stroke patients than in matched control subjects, and paradoxical embolism has been suggested as the main mechanism of stroke in-this situation. The present study was designed to test this hypothesis. Methods: Sixty-eight consecutive patients under 55 years of age presenting with an ischemic stroke had an extensive workup, including transesophageal echocardiography with contrast. We compared the prevalence of criteria for the diagnosis of paradoxical embolism in patients with and without a patent foramen ovale. Results: A patent foramen ovale was found in 32 patients (47%). A Valsalva-provoking activity was present at stroke onset in six patients with a patent foramen ovale and in eight patients with no patent foramen ovale (X(sup 2)=0.1, nonsignificant). Clinical/radiological features suggestive of an embolic mechanism were not more frequent in patients with a patent foramen ovale. Clinical evidence of deep vein thrombosis was present in one patient with a patent foramen ovale and in none of the others. No occult venous thrombosis was found in a subgroup of patients with a patent foramen ovale and no definite cause for stroke who underwent venography (n=13). Conclusions. Our results do not support the hypothesis that paradoxical embolism is the primary mechanism of stroke in patients with a patent foramen ovale. (Stroke 1993;24:31-34) KEY WORDS e cerebral ischemia e embolism foramen ovale, patent

An Applet for the Investigation of Simpson's Paradox

ERIC Educational Resources Information Center

Schneiter, Kady; Symanzik, Jurgen

2013-01-01

This article describes an applet that facilitates investigation of Simpson's Paradox in the context of a number of real and hypothetical data sets. The applet builds on the Baker-Kramer graphical representation for Simpson's Paradox. The implementation and use of the applet are explained. This is followed by a description of how the applet has…

An alternative resolution to the Mansuripur paradox

NASA Astrophysics Data System (ADS)

Redfern, Francis

2016-04-01

In 2013 an article published online by the journal Science declared that the paradox proposed by Masud Mansuripur was resolved. This paradox concerns a point charge-Amperian magnetic dipole system as seen in a frame of reference where they are at rest and one in which they are moving. In the latter frame an electric dipole appears on the magnetic dipole. A torque is then exerted upon the electric dipole by the point charge, a torque that is not observed in the at-rest frame. Mansuripur points out this violates the relativity principle and suggests the Lorentz force responsible for the torque be replaced by the Einstein-Laub force. The resolution of the paradox reported by Science, based on numerous papers in the physics literature, preserves the Lorentz force but depends on the concept of hidden momentum. Here I propose a different resolution based on the overlooked fact that the charge-magnetic dipole system contains linear and angular electromagnetic field momentum. The time rate of change of the field angular-momentum in the frame through which the system is moving cancels that due to the charge-electric dipole interaction. From this point of view hidden momentum is not needed in the resolution of the paradox.

Parrondo's games based on complex networks and the paradoxical effect.

PubMed

Ye, Ye; Wang, Lu; Xie, Nenggang

2013-01-01

Parrondo's games were first constructed using a simple tossing scenario, which demonstrates the following paradoxical situation: in sequences of games, a winning expectation may be obtained by playing the games in a random order, although each game (game A or game B) in the sequence may result in losing when played individually. The available Parrondo's games based on the spatial niche (the neighboring environment) are applied in the regular networks. The neighbors of each node are the same in the regular graphs, whereas they are different in the complex networks. Here, Parrondo's model based on complex networks is proposed, and a structure of game B applied in arbitrary topologies is constructed. The results confirm that Parrondo's paradox occurs. Moreover, the size of the region of the parameter space that elicits Parrondo's paradox depends on the heterogeneity of the degree distributions of the networks. The higher heterogeneity yields a larger region of the parameter space where the strong paradox occurs. In addition, we use scale-free networks to show that the network size has no significant influence on the region of the parameter space where the strong or weak Parrondo's paradox occurs. The region of the parameter space where the strong Parrondo's paradox occurs reduces slightly when the average degree of the network increases.

Obesity and the obesity paradox in heart failure.

PubMed

Gupta, Pritha P; Fonarow, Gregg C; Horwich, Tamara B

2015-02-01

Obesity has reached epidemic proportions in the general population and is associated with an increased risk for the development of new-onset heart failure (HF). However, in acute and chronic HF, overweight and mild to moderate obesity is associated with substantially improved survival compared with normal weight. This phenomenon has been termed the "obesity paradox" in HF. The majority of data pertaining to the obesity paradox identifies obesity with body mass index; however, the reliability of this method has been questioned. Newer studies have explored the use of other measures of body fat and body composition, including waist circumference, waist-to-hip ratio, skinfold thickness, and bioelectrical impedance analysis of body composition. The relationship between the obesity paradox and cardiorespiratory fitness in HF is also discussed in this review, and we explore the various potential explanations for the obesity paradox and summarize the current evidence and guidelines for intentional weight loss treatments for HF in the obese population. Copyright © 2015 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

An FPGA-Based Silicon Neuronal Network with Selectable Excitability Silicon Neurons

PubMed Central

Li, Jing; Katori, Yuichi; Kohno, Takashi

2012-01-01

This paper presents a digital silicon neuronal network which simulates the nerve system in creatures and has the ability to execute intelligent tasks, such as associative memory. Two essential elements, the mathematical-structure-based digital spiking silicon neuron (DSSN) and the transmitter release based silicon synapse, allow us to tune the excitability of silicon neurons and are computationally efficient for hardware implementation. We adopt mixed pipeline and parallel structure and shift operations to design a sufficient large and complex network without excessive hardware resource cost. The network with 256 full-connected neurons is built on a Digilent Atlys board equipped with a Xilinx Spartan-6 LX45 FPGA. Besides, a memory control block and USB control block are designed to accomplish the task of data communication between the network and the host PC. This paper also describes the mechanism of associative memory performed in the silicon neuronal network. The network is capable of retrieving stored patterns if the inputs contain enough information of them. The retrieving probability increases with the similarity between the input and the stored pattern increasing. Synchronization of neurons is observed when the successful stored pattern retrieval occurs. PMID:23269911

A Simple Explanation of the Classic Hydrostatic Paradox

ERIC Educational Resources Information Center

Kontomaris, Stylianos-Vasileios; Malamou, Anna

2016-01-01

An interesting problem in fluid mechanics, with significant educational importance, is the classic hydrostatic paradox. The hydrostatic paradox states the fact that in different shaped containers, with the same base area, which are filled with a liquid of the same height, the applied force by the liquid on the base of each container is exactly the…

DETECTION AND IMPLICATIONS OF EARLY AGROBACTERIUM TUMEFACIENS INFECTION OF PARADOX SEEDS AND SEEDLINGS

USDA-ARS?s Scientific Manuscript database

Paradox (Juglans hindsii x J. regia), the dominant rootstock used in California, USA walnut production, has many desirable horticultural characteristics, but is highly susceptible to crown gall. Crown gall, caused by the soil-borne bacterium Agrobacterium tumefaciens, can not be consistently control...

An experimental study of the Online Information Paradox: Does en-route information improve road network performance?

PubMed

Wijayaratna, Kasun P; Dixit, Vinayak V; Denant-Boemont, Laurent; Waller, S Travis

2017-01-01

This study investigates the empirical presence of a theoretical transportation paradox, defined as the "Online Information Paradox" (OIP). The paradox suggests that, for certain road networks, the provision of online information deteriorate travel conditions for all users of that network relative to the situation where no online information is provided to users. The analytical presence of the paradox was derived for a specific network structure by using two equilibrium models, the first being the Expected User Equilibrium (EUE) solution (no information scenario) and the other being the User Equilibrium with Recourse (UER) solution (with information scenario). An incentivised computerised route choice game was designed using the concepts of experimental economics and administered in a controlled laboratory environment to investigate the physical presence of the paradox. Aggregate statistics of path flows and Total System Travel Costs (TSTC) were used to compare the experimental results with the theoretical findings. A total of 12 groups of 12 participants completed the experiment and the OIP and the occurrence of the OIP being significant was observed in 11 of the 12 cases. Though information increased travel costs for users on average, it reduced the volatility of travel costs experienced in the no information scenario indicating that information can achieve a more reliable system. Further replications of similar experiments and more importantly field based identification of the phenomena will force transport professionals to be aware of the emergence of the paradox. In addition, studies such as this emphasise the need for the adoption of adaptive traffic assignment techniques to appropriately model the acquisition of information on a road network.

Taotie neurons regulate appetite in Drosophila

PubMed Central

Zhan, Yin Peng; Liu, Li; Zhu, Yan

2016-01-01

The brain has an essential role in maintaining a balance between energy intake and expenditure of the body. Deciphering the processes underlying the decision-making for timely feeding of appropriate amounts may improve our understanding of physiological and psychological disorders related to feeding control. Here, we identify a group of appetite-enhancing neurons in a behavioural screen for flies with increased appetite. Manipulating the activity of these neurons, which we name Taotie neurons, induces bidirectional changes in feeding motivation. Long-term stimulation of Taotie neurons results in flies with highly obese phenotypes. Furthermore, we show that the in vivo activity of Taotie neurons in the neuroendocrine region reflects the hunger/satiety states of un-manipulated animals, and that appetitive-enhancing Taotie neurons control the secretion of insulin, a known regulator of feeding behaviour. Thus, our study reveals a new set of neurons regulating feeding behaviour in the high brain regions that represents physiological hunger states and control feeding behaviour in Drosophila. PMID:27924813

New paradoxes of risky decision making.

PubMed

Birnbaum, Michael H

2008-04-01

During the last 25 years, prospect theory and its successor, cumulative prospect theory, replaced expected utility as the dominant descriptive theories of risky decision making. Although these models account for the original Allais paradoxes, 11 new paradoxes show where prospect theories lead to self-contradiction or systematic false predictions. The new findings are consistent with and, in several cases, were predicted in advance by simple "configural weight" models in which probability-consequence branches are weighted by a function that depends on branch probability and ranks of consequences on discrete branches. Although they have some similarities to later models called "rank-dependent utility," configural weight models do not satisfy coalescing, the assumption that branches leading to the same consequence can be combined by adding their probabilities. Nor do they satisfy cancellation, the "independence" assumption that branches common to both alternatives can be removed. The transfer of attention exchange model, with parameters estimated from previous data, correctly predicts results with all 11 new paradoxes. Apparently, people do not frame choices as prospects but, instead, as trees with branches.

Intimate partner violence against women and the Nordic paradox.

PubMed

Gracia, Enrique; Merlo, Juan

2016-05-01

Nordic countries are the most gender equal countries in the world, but at the same time they have disproportionally high prevalence rates of intimate partner violence (IPV) against women. High prevalence of IPV against women, and high levels of gender equality would appear contradictory, but these apparently opposite statements appear to be true in Nordic countries, producing what could be called the 'Nordic paradox'. Despite this paradox being one of the most puzzling issues in the field, this is a research question rarely asked, and one that remains unanswered. This paper explores a number of theoretical and methodological issues that may help to understand this paradox. Efforts to understand the Nordic paradox may provide an avenue to guide new research on IPV and to respond to this major public health problem in a more effective way. Copyright © 2016 Elsevier Ltd. All rights reserved.

Mitochondrial Dynamics Mediated by Mitofusin 1 Is Required for POMC Neuron Glucose-Sensing and Insulin Release Control.

PubMed

Ramírez, Sara; Gómez-Valadés, Alicia G; Schneeberger, Marc; Varela, Luis; Haddad-Tóvolli, Roberta; Altirriba, Jordi; Noguera, Eduard; Drougard, Anne; Flores-Martínez, Álvaro; Imbernón, Mónica; Chivite, Iñigo; Pozo, Macarena; Vidal-Itriago, Andrés; Garcia, Ainhoa; Cervantes, Sara; Gasa, Rosa; Nogueiras, Ruben; Gama-Pérez, Pau; Garcia-Roves, Pablo M; Cano, David A; Knauf, Claude; Servitja, Joan-Marc; Horvath, Tamas L; Gomis, Ramon; Zorzano, Antonio; Claret, Marc

2017-06-06

Proopiomelanocortin (POMC) neurons are critical sensors of nutrient availability implicated in energy balance and glucose metabolism control. However, the precise mechanisms underlying nutrient sensing in POMC neurons remain incompletely understood. We show that mitochondrial dynamics mediated by Mitofusin 1 (MFN1) in POMC neurons couple nutrient sensing with systemic glucose metabolism. Mice lacking MFN1 in POMC neurons exhibited defective mitochondrial architecture remodeling and attenuated hypothalamic gene expression programs during the fast-to-fed transition. This loss of mitochondrial flexibility in POMC neurons bidirectionally altered glucose sensing, causing abnormal glucose homeostasis due to defective insulin secretion by pancreatic β cells. Fed mice lacking MFN1 in POMC neurons displayed enhanced hypothalamic mitochondrial oxygen flux and reactive oxygen species generation. Central delivery of antioxidants was able to normalize the phenotype. Collectively, our data posit MFN1-mediated mitochondrial dynamics in POMC neurons as an intrinsic nutrient-sensing mechanism and unveil an unrecognized link between this subset of neurons and insulin release. Copyright © 2017 Elsevier Inc. All rights reserved.

[Single and Network Neuron Activity of Subthalamic Nucleus at Impulsive and Delayed (Self-Control) Reactions in Choice Behavior].

PubMed

Sidorina, V V; Gerasimova, Yu A; Kuleshova, E P; Merzhanova, G Kh

2015-01-01

During our experiments on cats was investigated the subthalamic neuron activity at different types of behavior in case of reinforcement choice depending on its value and availability. In chronic experiences the multiunit activity in subthalamic nucleus (STN) and orbitofrontal cortex (FC) has been recorded. Multiunit activity was analyzed over frequency and network properties of spikes. It was shown, that STN neurons reaction to different reinforcements and conditional stimulus at short- or long-delay reactions was represented by increasing or decreasing of frequency of single neurons. However the same STN neu- rons responded with increasing of frequency of single neuron during expectation of mix-bread-meat and decreasing--during the meat expectation. It has been revealed, that the number of STN interneuron interactions was authentic more at impulsive behavior than at self-control choice of behavior. The number of interactions between FC and STN neurons within intervals of 0-30 Ms was authentic more at display impulsive than during self-control behavior. These results suppose that FC and STN neurons participate in integration of reinforcement estimation; and distinctions in a choice of behavior are defined by the local and distributed interneuron interactions of STN and FC.

Treatment Strategies for Paradoxical Hypertension Following Surgical Correction of Coarctation of the Aorta in Children

PubMed Central

Zwijsen, Eline G.

2017-01-01

Background: Paradoxical hypertension after repair of coarctation of the aorta is a well-known phenomenon. The pathogenesis involves the activation of the sympathetic nervous system (first phase) and renin–angiotensin system (second phase). Only a limited number of different treatment strategies have been published in the literature, without any comparative studies. Methods: Our aim was to describe the current international practice variation surrounding pharmacological treatment currently being employed to treat paradoxical hypertension following the repair of coarctation of the aorta in children. We performed an online survey among 197 members of the Pediatric Cardiac Intensive Care Society. We also conducted a systematic review of the literature regarding the treatment of paradoxical hypertension. Results: Eighty-eight people (45%), from 62 different centers, responded and answered the questions regarding blood pressure control. Nitroprusside is the first drug of choice for initial blood pressure control in 66% of respondents, esmolol in 11%, labetalol in 11%, and angiotensin-converting enzyme inhibitors (ACEIs) are used by 3% of respondents. For oral blood pressure control after discharge from the pediatric intensive care unit, 75% of respondents use ACEIs, 18% use labetalol, and 12% use other beta-blockers (propranolol, carvedilol, atenolol, metoprolol). The systematic review identified 14 articles reporting pharmacological treatment of direct postoperative hypertension following coarctation repair. Conclusion: There is wide practice variability, due to the lack of sufficient compelling evidence. The majority (66%) of caregivers use nitroprusside to control blood pressure in the acute postoperative phase. The ACEIs are the drug of choice for chronic blood pressure control. PMID:28520538

Scalable Control of Mounting and Attack by ESR1+ Neurons in the Ventromedial Hypothalamus

PubMed Central

Lee, Hyosang; Kim, Dong-Wook; Remedios, Ryan; Anthony, Todd E.; Chang, Angela; Madisen, Linda; Zeng, Hongkui; Anderson, David J.

2014-01-01

Social behaviors, such as aggression or mating, proceed through a series of appetitive and consummatory phases1 that are associated with increasing levels of arousal2. How such escalation is encoded in the brain, and linked to behavioral action selection, remains an important unsolved problem in neuroscience. The ventrolateral subdivision of the murine ventromedial hypothalamus (VMHvl) contains neurons whose activity increases during male-male and male-female social encounters. Non-cell type-specific optogenetic activation of this region elicited attack behavior, but not mounting3. We have identified a subset of VMHvl neurons marked by the estrogen receptor 1 (Esr1), and investigated their role in male social behavior. Optogenetic manipulations indicated that Esr1+ (but not Esr1-) neurons are sufficient to initiate attack, and that their activity is continuously required during ongoing agonistic behavior. Surprisingly, weaker optogenetic activation of these neurons promoted mounting behavior, rather than attack, towards both males and females, as well as sniffing and close investigation (CI). Increasing photostimulation intensity could promote a transition from CI and mounting to attack, within a single social encounter. Importantly, time-resolved optogenetic inhibition experiments revealed requirements for Esr1+ neurons in both the appetitive (investigative) and the consummatory phases of social interactions. Combined optogenetic activation and calcium imaging experiments in vitro, as well as c-Fos analysis in vivo, indicated that increasing photostimulation intensity increases both the number of active neurons and the average level of activity per neuron. These data suggest that Esr1+ neurons in VMHvl control the progression of a social encounter from its appetitive through its consummatory phases, in a scalable manner that reflects the number or type of active neurons in the population. PMID:24739975

Navigating Instructional Dialectics: Empirical Exploration of Paradox in Teaching

ERIC Educational Resources Information Center

Thompson, Blair; Rudick, C. Kyle; Kerssen-Griep, Jeff; Golsan, Kathryn

2018-01-01

Navigating contradiction represents an integral part of the teaching process. While educational literature has discussed the paradoxes that teachers experience in the classroom, minimal empirical research has analyzed the strategies teachers employ to address these paradoxes. Using relational dialectics as a theoretical framework for understanding…

The evolutionarily conserved transcription factor PRDM12 controls sensory neuron development and pain perception.

PubMed

Nagy, Vanja; Cole, Tiffany; Van Campenhout, Claude; Khoung, Thang M; Leung, Calvin; Vermeiren, Simon; Novatchkova, Maria; Wenzel, Daniel; Cikes, Domagoj; Polyansky, Anton A; Kozieradzki, Ivona; Meixner, Arabella; Bellefroid, Eric J; Neely, G Gregory; Penninger, Josef M

2015-01-01

PR homology domain-containing member 12 (PRDM12) belongs to a family of conserved transcription factors implicated in cell fate decisions. Here we show that PRDM12 is a key regulator of sensory neuronal specification in Xenopus. Modeling of human PRDM12 mutations that cause hereditary sensory and autonomic neuropathy (HSAN) revealed remarkable conservation of the mutated residues in evolution. Expression of wild-type human PRDM12 in Xenopus induced the expression of sensory neuronal markers, which was reduced using various human PRDM12 mutants. In Drosophila, we identified Hamlet as the functional PRDM12 homolog that controls nociceptive behavior in sensory neurons. Furthermore, expression analysis of human patient fibroblasts with PRDM12 mutations uncovered possible downstream target genes. Knockdown of several of these target genes including thyrotropin-releasing hormone degrading enzyme (TRHDE) in Drosophila sensory neurons resulted in altered cellular morphology and impaired nociception. These data show that PRDM12 and its functional fly homolog Hamlet are evolutionary conserved master regulators of sensory neuronal specification and play a critical role in pain perception. Our data also uncover novel pathways in multiple species that regulate evolutionary conserved nociception.

What Exactly is the Information Paradox?

NASA Astrophysics Data System (ADS)

Mathur, S. D.

The black hole information paradox tells us something important about the way quantum mechanics and gravity fit together. In these lectures I try to give a pedagogical review of the essential physics leading to the paradox, using mostly pictures. Hawking's argument is recast as a "theorem": if quantum gravity effects are confined to within a given length scale and the vacuum is assumed to be unique, then there will be information loss. We conclude with a brief summary of how quantum effects in string theory violate the first condition and make the interior of the hole a "fuzzball".

PROS-1/Prospero Is a Major Regulator of the Glia-Specific Secretome Controlling Sensory-Neuron Shape and Function in C. elegans.

PubMed

Wallace, Sean W; Singhvi, Aakanksha; Liang, Yupu; Lu, Yun; Shaham, Shai

2016-04-19

Sensory neurons are an animal's gateway to the world, and their receptive endings, the sites of sensory signal transduction, are often associated with glia. Although glia are known to promote sensory-neuron functions, the molecular bases of these interactions are poorly explored. Here, we describe a post-developmental glial role for the PROS-1/Prospero/PROX1 homeodomain protein in sensory-neuron function in C. elegans. Using glia expression profiling, we demonstrate that, unlike previously characterized cell fate roles, PROS-1 functions post-embryonically to control sense-organ glia-specific secretome expression. PROS-1 functions cell autonomously to regulate glial secretion and membrane structure, and non-cell autonomously to control the shape and function of the receptive endings of sensory neurons. Known glial genes controlling sensory-neuron function are PROS-1 targets, and we identify additional PROS-1-dependent genes required for neuron attributes. Drosophila Prospero and vertebrate PROX1 are expressed in post-mitotic sense-organ glia and astrocytes, suggesting conserved roles for this class of transcription factors. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Loss of Action via Neurotensin-Leptin Receptor Neurons Disrupts Leptin and Ghrelin-Mediated Control of Energy Balance.

PubMed

Brown, Juliette A; Bugescu, Raluca; Mayer, Thomas A; Gata-Garcia, Adriana; Kurt, Gizem; Woodworth, Hillary L; Leinninger, Gina M

2017-05-01

The hormones ghrelin and leptin act via the lateral hypothalamic area (LHA) to modify energy balance, but the underlying neural mechanisms remain unclear. We investigated how leptin and ghrelin engage LHA neurons to modify energy balance behaviors and whether there is any crosstalk between leptin and ghrelin-responsive circuits. We demonstrate that ghrelin activates LHA neurons expressing hypocretin/orexin (OX) to increase food intake. Leptin mediates anorectic actions via separate neurons expressing the long form of the leptin receptor (LepRb), many of which coexpress the neuropeptide neurotensin (Nts); we refer to these as NtsLepRb neurons. Because NtsLepRb neurons inhibit OX neurons, we hypothesized that disruption of the NtsLepRb neuronal circuit would impair both NtsLepRb and OX neurons from responding to their respective hormonal cues, thus compromising adaptive energy balance. Indeed, mice with developmental deletion of LepRb specifically from NtsLepRb neurons exhibit blunted adaptive responses to leptin and ghrelin that discoordinate the mesolimbic dopamine system and ingestive and locomotor behaviors, leading to weight gain. Collectively, these data reveal a crucial role for LepRb in the proper formation of LHA circuits, and that NtsLepRb neurons are important neuronal hubs within the LHA for hormone-mediated control of ingestive and locomotor behaviors. Copyright © 2017 Endocrine Society.

Control of alternative splicing by forskolin through hnRNP K during neuronal differentiation

PubMed Central

Cao, Wenguang; Razanau, Aleh; Feng, Dairong; Lobo, Vincent G.; Xie, Jiuyong

2012-01-01

The molecular basis of cell signal-regulated alternative splicing at the 3′ splice site remains largely unknown. We isolated a protein kinase A-responsive ribonucleic acid (RNA) element from a 3′ splice site of the synaptosomal-associated protein 25 (Snap25) gene for forskolin-inhibited splicing during neuronal differentiation of rat pheochromocytoma PC12 cells. The element binds specifically to heterogeneous nuclear ribonucleo protein (hnRNP) K in a phosphatase-sensitive way, which directly competes with the U2 auxiliary factor U2AF65, an essential component of early spliceosomes. Transcripts with similarly localized hnRNP K target motifs upstream of alternative exons are enriched in genes often associated with neurological diseases. We show that such motifs upstream of the Runx1 exon 6 also bind hnRNP K, and importantly, hnRNP K is required for forskolin-induced repression of the exon. Interestingly, this exon encodes the peptide domain that determines the switch of the transcriptional repressor/activator activity of Runx1, a change known to be critical in specifying neuron lineages. Consistent with an important role of the target genes in neurons, knocking down hnRNP K severely disrupts forskolin-induced neurite growth. Thus, through hnRNP K, the neuronal differentiation stimulus forskolin targets a critical 3′ splice site component of the splicing machinery to control alternative splicing of crucial genes. This also provides a regulated direct competitor of U2AF65 for cell signal control of 3′ splice site usage. PMID:22684629

Scrounging by foragers can resolve the paradox of enrichment

PubMed Central

2017-01-01

Theoretical models of predator–prey systems predict that sufficient enrichment of prey can generate large amplitude limit cycles, paradoxically causing a high risk of extinction (the paradox of enrichment). Although real ecological communities contain many gregarious species, whose foraging behaviour should be influenced by socially transmitted information, few theoretical studies have examined the possibility that social foraging might resolve this paradox. I considered a predator population in which individuals play the producer–scrounger foraging game in one-prey-one-predator and two-prey-one-predator systems. I analysed the stability of a coexisting equilibrium point in the one-prey system and that of non-equilibrium dynamics in the two-prey system. The results revealed that social foraging could stabilize both systems, and thereby resolve the paradox of enrichment when scrounging behaviour (i.e. kleptoparasitism) is prevalent in predators. This suggests a previously neglected mechanism underlying a powerful effect of group-living animals on the sustainability of ecological communities. PMID:28405371

Resolving the biodiversity paradox

Treesearch

James S. Clark; Mike Dieta; Sukhendu Chakraborty; Pankaj K.Ibeanez Agarwal; Shannon LaDeau; Mike Wolosin

2007-01-01

The paradox of biodiversity involves three elements, (i) mathematical models predict that species must differ in specific ways in order to coexist as stable ecological communities, (ii) such differences are difficult to identify, yet (iii) there is widespread evidence of stability in natural communities.

Setting Standards: Confronting Paradox.

ERIC Educational Resources Information Center

Doecke, Brenton; Gill, Margaret

2001-01-01

Discusses implications of the issues of continuity and discontinuity, commonality and difference, congruity and paradox as they engage the research team, the industry partners, and the teachers around Australia who constitute the STELLA (Standards for Teachers of English Language and Literacy in Australia) project. (RS)

Fine-tuned SRF activity controls asymmetrical neuronal outgrowth: implications for cortical migration, neural tissue lamination and circuit assembly

PubMed Central

Scandaglia, Marilyn; Benito, Eva; Morenilla-Palao, Cruz; Fiorenza, Anna; del Blanco, Beatriz; Coca, Yaiza; Herrera, Eloísa; Barco, Angel

2015-01-01

The stimulus-regulated transcription factor Serum Response Factor (SRF) plays an important role in diverse neurodevelopmental processes related to structural plasticity and motile functions, although its precise mechanism of action has not yet been established. To further define the role of SRF in neural development and distinguish between cell-autonomous and non cell-autonomous effects, we bidirectionally manipulated SRF activity through gene transduction assays that allow the visualization of individual neurons and their comparison with neighboring control cells. In vitro assays showed that SRF promotes survival and filopodia formation and is required for normal asymmetric neurite outgrowth, indicating that its activation favors dendrite enlargement versus branching. In turn, in vivo experiments demonstrated that SRF-dependent regulation of neuronal morphology has important consequences in the developing cortex and retina, affecting neuronal migration, dendritic and axonal arborization and cell positioning in these laminated tissues. Overall, our results show that the controlled and timely activation of SRF is essential for the coordinated growth of neuronal processes, suggesting that this event regulates the switch between neuronal growth and branching during developmental processes. PMID:26638868

Molecular pathological epidemiology gives clues to paradoxical findings.

PubMed

Nishihara, Reiko; VanderWeele, Tyler J; Shibuya, Kenji; Mittleman, Murray A; Wang, Molin; Field, Alison E; Giovannucci, Edward; Lochhead, Paul; Ogino, Shuji

2015-10-01

A number of epidemiologic studies have described what appear to be paradoxical associations, where an incongruous relationship is observed between a certain well-established risk factor for disease incidence and favorable clinical outcome among patients with that disease. For example, the "obesity paradox" represents the association between obesity and better survival among patients with a certain disease such as coronary heart disease. Paradoxical observations cause vexing clinical and public health problems as they raise questions on causal relationships and hinder the development of effective interventions. Compelling evidence indicates that pathogenic processes encompass molecular alterations within cells and the microenvironment, influenced by various exogenous and endogenous exposures, and that interpersonal heterogeneity in molecular pathology and pathophysiology exists among patients with any given disease. In this article, we introduce methods of the emerging integrative interdisciplinary field of molecular pathological epidemiology (MPE), which is founded on the unique disease principle and disease continuum theory. We analyze and decipher apparent paradoxical findings, utilizing the MPE approach and available literature data on tumor somatic genetic and epigenetic characteristics. Through our analyses in colorectal cancer, renal cell carcinoma, and glioblastoma (malignant brain tumor), we can readily explain paradoxical associations between disease risk factors and better prognosis among disease patients. The MPE paradigm and approach can be applied to not only neoplasms but also various non-neoplastic diseases where there exists indisputable ubiquitous heterogeneity of pathogenesis and molecular pathology. The MPE paradigm including consideration of disease heterogeneity plays an essential role in advancements of precision medicine and public health.

Disability reconsidered: the paradox of physical therapy.

PubMed

Roush, Susan E; Sharby, Nancy

2011-12-01

The purposes of this perspective article are: (1) to explore models of disability from the perspective of the academic discipline of disability studies (DS), (2) to consider the paradox of improving functional capacities while valuing disability as diversity, (3) to identify how physical therapy's use of the International Classification of Functioning, Disability and Health (ICF) disablement model intersects with various disability models, and (4) to apply this broader understanding of disability to physical therapist practice, education, and research. The DS literature has been critical of rehabilitation professionals, particularly targeting the medical model of disability. In contrast, advocates for a social model of disability recognize disability as diversity. It is paradoxical for physical therapy to simultaneously work to ameliorate disability while celebrating it as diversity. The ICF biopsychosocial disablement model offers a mechanism to practice within this paradox and suggests that it is no longer sufficient to conceptualize disability as a purely individual matter that requires attention in isolation from the impact of the larger society.

Reinterpretaion of the friendship paradox

NASA Astrophysics Data System (ADS)

Fu, Jingcheng; Wu, Jianliang

The friendship paradox (FP) is a sociological phenomenon stating that most people have fewer friends than their friends do. It is to say that in a social network, the number of friends that most individuals have is smaller than the average number of friends of friends. This has been verified by Feld. We call this interpreting method mean value version. But is it the best choice to portray the paradox? In this paper, we propose a probability method to reinterpret this paradox, and we illustrate that the explanation using our method is more persuasive. An individual satisfies the FP if his (her) randomly chosen friend has more friends than him (her) with probability not less than 1/2. Comparing the ratios of nodes satisfying the FP in networks, rp, we can see that the probability version is stronger than the mean value version in real networks both online and offline. We also show some results about the effects of several parameters on rp in random network models. Most importantly, rp is a quadratic polynomial of the power law exponent γ in Price model, and rp is higher when the average clustering coefficient is between 0.4 and 0.5 in Petter-Beom (PB) model. The introduction of the probability method to FP can shed light on understanding the network structure in complex networks especially in social networks.

Autoreceptor control of peptide/neurotransmitter corelease from PDF neurons determines allocation of circadian activity in drosophila.

PubMed

Choi, Charles; Cao, Guan; Tanenhaus, Anne K; McCarthy, Ellena V; Jung, Misun; Schleyer, William; Shang, Yuhua; Rosbash, Michael; Yin, Jerry C P; Nitabach, Michael N

2012-08-30

Drosophila melanogaster flies concentrate behavioral activity around dawn and dusk. This organization of daily activity is controlled by central circadian clock neurons, including the lateral-ventral pacemaker neurons (LN(v)s) that secrete the neuropeptide PDF (pigment dispersing factor). Previous studies have demonstrated the requirement for PDF signaling to PDF receptor (PDFR)-expressing dorsal clock neurons in organizing circadian activity. Although LN(v)s also express functional PDFR, the role of these autoreceptors has remained enigmatic. Here, we show that (1) PDFR activation in LN(v)s shifts the balance of circadian activity from evening to morning, similar to behavioral responses to summer-like environmental conditions, and (2) this shift is mediated by stimulation of the Gα,s-cAMP pathway and a consequent change in PDF/neurotransmitter corelease from the LN(v)s. These results suggest another mechanism for environmental control of the allocation of circadian activity and provide new general insight into the role of neuropeptide autoreceptors in behavioral control circuits. Copyright © 2012 The Authors. Published by Elsevier Inc. All rights reserved.

Neuron matters: electric activation of neuronal tissue is dependent on the interaction between the neuron and the electric field.

PubMed

Ye, Hui; Steiger, Amanda

2015-08-12

In laboratory research and clinical practice, externally-applied electric fields have been widely used to control neuronal activity. It is generally accepted that neuronal excitability is controlled by electric current that depolarizes or hyperpolarizes the excitable cell membrane. What determines the amount of polarization? Research on the mechanisms of electric stimulation focus on the optimal control of the field properties (frequency, amplitude, and direction of the electric currents) to improve stimulation outcomes. Emerging evidence from modeling and experimental studies support the existence of interactions between the targeted neurons and the externally-applied electric fields. With cell-field interaction, we suggest a two-way process. When a neuron is positioned inside an electric field, the electric field will induce a change in the resting membrane potential by superimposing an electrically-induced transmembrane potential (ITP). At the same time, the electric field can be perturbed and re-distributed by the cell. This cell-field interaction may play a significant role in the overall effects of stimulation. The redistributed field can cause secondary effects to neighboring cells by altering their geometrical pattern and amount of membrane polarization. Neurons excited by the externally-applied electric field can also affect neighboring cells by ephaptic interaction. Both aspects of the cell-field interaction depend on the biophysical properties of the neuronal tissue, including geometric (i.e., size, shape, orientation to the field) and electric (i.e., conductivity and dielectricity) attributes of the cells. The biophysical basis of the cell-field interaction can be explained by the electromagnetism theory. Further experimental and simulation studies on electric stimulation of neuronal tissue should consider the prospect of a cell-field interaction, and a better understanding of tissue inhomogeneity and anisotropy is needed to fully appreciate the neural

Paradoxical Sleep Deprivation Causes Cardiac Dysfunction and the Impairment Is Attenuated by Resistance Training.

PubMed

Giampá, Sara Quaglia de Campos; Mônico-Neto, Marcos; de Mello, Marco Tulio; Souza, Helton de Sá; Tufik, Sergio; Lee, Kil Sun; Koike, Marcia Kiyomi; Dos Santos, Alexandra Alberta; Antonio, Ednei Luiz; Serra, Andrey Jorge; Tucci, Paulo José Ferreira; Antunes, Hanna Karen Moreira

2016-01-01

Paradoxical sleep deprivation activates the sympathetic nervous system and the hypothalamus-pituitary-adrenal axis, subsequently interfering with the cardiovascular system. The beneficial effects of resistance training are related to hemodynamic, metabolic and hormonal homeostasis. We hypothesized that resistance training can prevent the cardiac remodeling and dysfunction caused by paradoxical sleep deprivation. Male Wistar rats were distributed into four groups: control (C), resistance training (RT), paradoxical sleep deprivation for 96 hours (PSD96) and both resistance training and sleep deprivation (RT/PSD96). Doppler echocardiograms, hemodynamics measurements, cardiac histomorphometry, hormonal profile and molecular analysis were evaluated. Compared to the C group, PSD96 group had a higher left ventricular systolic pressure, heart rate and left atrium index. In contrast, the left ventricle systolic area and the left ventricle cavity diameter were reduced in the PSD96 group. Hypertrophy and fibrosis were also observed. Along with these alterations, reduced levels of serum testosterone and insulin-like growth factor-1 (IGF-1), as well as increased corticosterone and angiotensin II, were observed in the PSD96 group. Prophylactic resistance training attenuated most of these changes, except angiotensin II, fibrosis, heart rate and concentric remodeling of left ventricle, confirmed by the increased of NFATc3 and GATA-4, proteins involved in the pathologic cardiac hypertrophy pathway. Resistance training effectively attenuates cardiac dysfunction and hormonal imbalance induced by paradoxical sleep deprivation.

Where Was Everybody? Olaf Stapledon and the Fermi Paradox

NASA Astrophysics Data System (ADS)

Baxter, S.

In 1948 Olaf Stapledon gave an address to the BIS in which he summarised his vision of mankind's cosmic future: `One can imagine some sort of cosmical community of worlds ...' One might ask, however, since the universe is vastly older than mankind, why races on other worlds have not already built such a community. This is a `Fermi Paradox' question. The Paradox is based on the observation that there has been time for extraterrestrial intelligence to arise and colonise the Galaxy many times over, yet we see no sign of such endeavours. In this paper Stapledon's novels are retrospectively analysed from the point of view of the Fermi Paradox. In Last and First Men (1930) humanity is forever isolated because life and mind are rare in the Galaxy, and interstellar distances are too large ever to be traversed. These are classic candidate Fermi `solutions'. The `solution' implicit in Star Maker (1937) might be criticised in that it posits that humanity lives at a special epoch, with the cosmically transforming development of interstellar travel occurring a `mere' ten billion years after mankind, in a universe supposedly ~200bn years old. Stapledon died in 1950, the year the Paradox was formulated, and was probably unaware of the Paradox. However to apply retrospectively Fermi thinking to Stapledon's cosmologies is to gain a new insight into the author's philosophy.

Control of abdominal and expiratory intercostal muscle activity during vomiting - Role of ventral respiratory group expiratory neurons

NASA Technical Reports Server (NTRS)

Miller, Alan D.; Tan, L. K.; Suzuki, Ichiro

1987-01-01

The role of ventral respiratory group (VRG) expiratory (E) neurons in the control of abdominal and internal intercostal muscle activity during vomiting was investigated in cats. Two series of experiments were performed: in one, the activity of VRG E neurons was recorded during fictive vomiting in cats that were decerebrated, paralyzed, and artificially ventilated; in the second, the abdominal muscle activity during vomiting was compared before and after sectioning the axons of descending VRG E neurons in decerebrate spontaneously breathing cats. The results show that about two-thirds of VRG E neurons that project at least as far caudally as the lower thoracic cord contribute to internal intercostal muscle activity during vomiting. The remaining VRG E neurons contribute to abdominal muscle activation. As shown by severing the axons of the VRG E neurons, other, as yet unidenified, inputs (either descending from the brain stem or arising from spinal reflexes) can also produce abdominal muscle activation.

Quantum Bayesian networks with application to games displaying Parrondo's paradox

NASA Astrophysics Data System (ADS)

Pejic, Michael

Bayesian networks and their accompanying graphical models are widely used for prediction and analysis across many disciplines. We will reformulate these in terms of linear maps. This reformulation will suggest a natural extension, which we will show is equivalent to standard textbook quantum mechanics. Therefore, this extension will be termed quantum. However, the term quantum should not be taken to imply this extension is necessarily only of utility in situations traditionally thought of as in the domain of quantum mechanics. In principle, it may be employed in any modelling situation, say forecasting the weather or the stock market---it is up to experiment to determine if this extension is useful in practice. Even restricting to the domain of quantum mechanics, with this new formulation the advantages of Bayesian networks can be maintained for models incorporating quantum and mixed classical-quantum behavior. The use of these will be illustrated by various basic examples. Parrondo's paradox refers to the situation where two, multi-round games with a fixed winning criteria, both with probability greater than one-half for one player to win, are combined. Using a possibly biased coin to determine the rule to employ for each round, paradoxically, the previously losing player now wins the combined game with probabilitygreater than one-half. Using the extended Bayesian networks, we will formulate and analyze classical observed, classical hidden, and quantum versions of a game that displays this paradox, finding bounds for the discrepancy from naive expectations for the occurrence of the paradox. A quantum paradox inspired by Parrondo's paradox will also be analyzed. We will prove a bound for the discrepancy from naive expectations for this paradox as well. Games involving quantum walks that achieve this bound will be presented.

Intrinsic Innate Immunity Fails To Control Herpes Simplex Virus and Vesicular Stomatitis Virus Replication in Sensory Neurons and Fibroblasts

PubMed Central

Rosato, Pamela C.

2014-01-01

ABSTRACT Herpes simplex virus 1 (HSV-1) establishes lifelong latent infections in the sensory neurons of the trigeminal ganglia (TG), wherein it retains the capacity to reactivate. The interferon (IFN)-driven antiviral response is critical for the control of HSV-1 acute replication. We therefore sought to further investigate this response in TG neurons cultured from adult mice deficient in a variety of IFN signaling components. Parallel experiments were also performed in fibroblasts isolated concurrently. We showed that HSV-1 replication was comparable in wild-type (WT) and IFN signaling-deficient neurons and fibroblasts. Unexpectedly, a similar pattern was observed for the IFN-sensitive vesicular stomatitis virus (VSV). Despite these findings, TG neurons responded to IFN-β pretreatment with STAT1 nuclear localization and restricted replication of both VSV and an HSV-1 strain deficient in γ34.5, while wild-type HSV-1 replication was unaffected. This was in contrast to fibroblasts in which all viruses were restricted by the addition of IFN-β. Taken together, these data show that adult TG neurons can mount an effective antiviral response only if provided with an exogenous source of IFN-β, and HSV-1 combats this response through γ34.5. These results further our understanding of the antiviral response of neurons and highlight the importance of paracrine IFN-β signaling in establishing an antiviral state. IMPORTANCE Herpes simplex virus 1 (HSV-1) is a ubiquitous virus that establishes a lifelong latent infection in neurons. Reactivation from latency can cause cold sores, blindness, and death from encephalitis. Humans with deficiencies in innate immunity have significant problems controlling HSV infections. In this study, we therefore sought to elucidate the role of neuronal innate immunity in the control of viral infection. Using neurons isolated from mice, we found that the intrinsic capacity of neurons to restrict virus replication was unaffected by the presence

Ca2+ paradox injury mediated through TRPC channels in mouse ventricular myocytes

PubMed Central

Kojima, Akiko; Kitagawa, Hirotoshi; Omatsu-Kanbe, Mariko; Matsuura, Hiroshi; Nosaka, Shuichi

2010-01-01

BACKGROUND AND PURPOSE The Ca2+ paradox is an important phenomenon associated with Ca2+ overload-mediated cellular injury in myocardium. The present study was undertaken to elucidate molecular and cellular mechanisms for the development of the Ca2+ paradox. EXPERIMENTAL APPROACH Fluorescence imaging was performed on fluo-3 loaded quiescent mouse ventricular myocytes using confocal laser scanning microscope. KEY RESULTS The Ca2+ paradox was readily evoked by restoration of the extracellular Ca2+ following 10–20 min of nominally Ca2+-free superfusion. The Ca2+ paradox was significantly reduced by blockers of transient receptor potential canonical (TRPC) channels (2-aminoethoxydiphenyl borate, Gd3+, La3+) and anti-TRPC1 antibody. The sarcoplasmic reticulum (SR) Ca2+ content, assessed by caffeine application, gradually declined during Ca2+-free superfusion, which was further accelerated by metabolic inhibition. Block of SR Ca2+ leak by tetracaine prevented Ca2+ paradox. The Na+/Ca2+ exchange (NCX) blocker KB-R7943 significantly inhibited Ca2+ paradox when applied throughout superfusion period, but had little effect when added for a period of 3 min before and during Ca2+ restoration. The SR Ca2+ content was better preserved during Ca2+ depletion by KB-R7943. Immunocytochemistry confirmed the expression of TRPC1, in addition to TRPC3 and TRPC4, in mouse ventricular myocytes. CONCLUSIONS AND IMPLICATIONS These results provide evidence that (i) the Ca2+ paradox is primarily mediated by Ca2+ entry through TRPC (probably TRPC1) channels that are presumably activated by SR Ca2+ depletion; and (ii) reverse mode NCX contributes little to the Ca2+ paradox, whereas inhibition of NCX during Ca2+ depletion improves SR Ca2+ loading, and is associated with reduced incidence of Ca2+ paradox in mouse ventricular myocytes. PMID:20718730

Orexin neurons are necessary for the circadian control of REM sleep.

PubMed

Kantor, Sandor; Mochizuki, Takatoshi; Janisiewicz, Agnieszka M; Clark, Erika; Nishino, Seiji; Scammell, Thomas E

2009-09-01

The orexin-producing neurons are hypothesized to be essential for the circadian control of sleep/wake behavior, but it remains unknown whether these rhythms are mediated by the orexin peptides or by other signaling molecules released by these neurons such as glutamate or dynorphin. To determine the roles of these neurotransmitters, we examined the circadian rhythms of sleep/wake behavior in mice lacking the orexin neurons (ataxin-3 [Atx] mice) and mice lacking just the orexin neuropeptides (orexin knockout [KO] mice). We instrumented mice for recordings of sleep-wake behavior, locomotor activity (LMA), and body temperature (Tb) and recorded behavior after 6 days in constant darkness. The amplitude of the rapid eye movement (REM) sleep rhythm was substantially reduced in Atx mice but preserved in orexin KO mice. This blunted rhythm in Atx mice was caused by an increase in the amount of REM sleep during the subjective night (active period) due to more transitions into REM sleep and longer REM sleep episodes. In contrast, the circadian variations of Tb, LMA, Wake, non-REM sleep, and cataplexy were normal, suggesting that the circadian timekeeping system and other output pathways are intact in both Atx and KO mice. These results indicate that the orexin neurons are necessary for the circadian suppression of REM sleep. Blunting of the REM sleep rhythm in Atx mice but not in orexin KO mice suggests that other signaling molecules such as dynorphin or glutamate may act in concert with orexins to suppress REM sleep during the active period.

Single neuron modeling and data assimilation in BNST neurons

NASA Astrophysics Data System (ADS)

Farsian, Reza

Neurons, although tiny in size, are vastly complicated systems, which are responsible for the most basic yet essential functions of any nervous system. Even the most simple models of single neurons are usually high dimensional, nonlinear, and contain many parameters and states which are unobservable in a typical neurophysiological experiment. One of the most fundamental problems in experimental neurophysiology is the estimation of these parameters and states, since knowing their values is essential in identification, model construction, and forward prediction of biological neurons. Common methods of parameter and state estimation do not perform well for neural models due to their high dimensionality and nonlinearity. In this dissertation, two alternative approaches for parameters and state estimation of biological neurons have been demonstrated: dynamical parameter estimation (DPE) and a Markov Chain Monte Carlo (MCMC) method. The first method uses elements of chaos control and synchronization theory for parameter and state estimation. MCMC is a statistical approach which uses a path integral formulation to evaluate a mean and an error bound for these unobserved parameters and states. These methods have been applied to biological system of neurons in Bed Nucleus of Stria Termialis neurons (BNST) of rats. State and parameters of neurons in both systems were estimated, and their value were used for recreating a realistic model and predicting the behavior of the neurons successfully. The knowledge of biological parameters can ultimately provide a better understanding of the internal dynamics of a neuron in order to build robust models of neuron networks.

Which Neurons Will Be the Engram - Activated Neurons and/or More Excitable Neurons?

PubMed

Kim, Ji-Il; Cho, Hye-Yeon; Han, Jin-Hee; Kaang, Bong-Kiun

2016-04-01

During past decades, the formation and storage principle of memory have received much attention in the neuroscience field. Although some studies have attempted to demonstrate the nature of the engram, elucidating the memory engram allocation mechanism was not possible because of the limitations of existing methods, which cannot specifically modulate the candidate neuronal population. Recently, the development of new techniques, which offer ways to mark and control specific populations of neurons, may accelerate solving this issue. Here, we review the recent advances, which have provided substantial evidence showing that both candidates (neuronal population that is activated by learning, and that has increased CREB level/excitability at learning) satisfy the criteria of the engram, which are necessary and sufficient for memory expression.

Which Neurons Will Be the Engram - Activated Neurons and/or More Excitable Neurons?

PubMed Central

Kim, Ji-il; Cho, Hye-Yeon; Han, Jin-Hee

2016-01-01

During past decades, the formation and storage principle of memory have received much attention in the neuroscience field. Although some studies have attempted to demonstrate the nature of the engram, elucidating the memory engram allocation mechanism was not possible because of the limitations of existing methods, which cannot specifically modulate the candidate neuronal population. Recently, the development of new techniques, which offer ways to mark and control specific populations of neurons, may accelerate solving this issue. Here, we review the recent advances, which have provided substantial evidence showing that both candidates (neuronal population that is activated by learning, and that has increased CREB level/excitability at learning) satisfy the criteria of the engram, which are necessary and sufficient for memory expression. PMID:27122991

Paradoxical Cerebral Fat Embolism in Revision Hip Surgery

PubMed Central

Piuzzi, Nicolás S.; Zanotti, Gerardo; Comba, Fernando M.; Buttaro, Martin A.; Piccaluga, Francisco

2014-01-01

The incidence of clinical fat embolism syndrome (FES) is low (<1%) whilst fat embolism (FE) of marrow fat appears to occur more often (Mellor and Soni (2001)). Paradoxical brain FE may occur in patients undergoing hip orthopedic surgery who have an undocumented patent foramen ovale (PFO). We report a case of an eighty-year-old male patient, who underwent a scheduled revision hip surgery suffering a paradoxical cerebral FE. PMID:25184065

Consistent resolution of some relativistic quantum paradoxes

NASA Astrophysics Data System (ADS)

Griffiths, Robert B.

2002-12-01

A relativistic version of the (consistent or decoherent) histories approach to quantum theory is developed on the basis of earlier work by Hartle, and used to discuss relativistic forms of the paradoxes of spherical wave packet collapse, Bohm's formulation of the Einstein-Podolsky-Rosen paradox, and Hardy's paradox. It is argued that wave function collapse is not needed for introducing probabilities into relativistic quantum mechanics, and in any case should never be thought of as a physical process. Alternative approaches to stochastic time dependence can be used to construct a physical picture of the measurement process that is less misleading than collapse models. In particular, one can employ a coarse-grained but fully quantum-mechanical description in which particles move along trajectories, with behavior under Lorentz transformations the same as in classical relativistic physics, and detectors are triggered by particles reaching them along such trajectories. States entangled between spacelike separate regions are also legitimate quantum descriptions, and can be consistently handled by the formalism presented here. The paradoxes in question arise because of using modes of reasoning which, while correct for classical physics, are inconsistent with the mathematical structure of quantum theory, and are resolved (or tamed) by using a proper quantum analysis. In particular, there is no need to invoke, nor any evidence for, mysterious long-range superluminal influences, and thus no incompatibility, at least from this source, between relativity theory and quantum mechanics.

Paradoxical Pain Perception in Posttraumatic Stress Disorder: The Unique Role of Anxiety and Dissociation.

PubMed

Defrin, Ruth; Schreiber, Shaul; Ginzburg, Karni

2015-10-01

Posttraumatic stress disorder (PTSD) and chronic pain often co-occur and exacerbate each other. Elucidating the mechanism of this co-occurrence therefore has clinical importance. Previously, patients with PTSD with chronic pain were found to demonstrate a unique paradoxical pain profile: hyperresponsiveness together with hyposensitivity to pain. Our aim was to examine whether 2 seemingly paradoxical facets of PTSD (anxiety and dissociation) underlie this paradoxical profile. Patients with PTSD (n = 32) and healthy control individuals (n = 43) underwent psychophysical testing and completed questionnaires. Patients with PTSD had higher pain thresholds and higher pain ratings to suprathreshold stimuli than control individuals. Pain thresholds were positively associated with dissociation levels and negatively associated with anxiety sensitivity levels. Experimental pain ratings were positively associated with anxiety sensitivity and negatively related to dissociation levels. Chronic pain intensity was associated with anxiety, anxiety sensitivity, and pain catastrophizing. It appears that reduced conscious attention toward incoming stimuli, resulting from dissociation, causes delayed response in pain threshold measurement, whereas biases toward threatening stimuli and decreased inhibition, possibly caused by increased anxiety, are responsible for the intensification of experimental and chronic pain. The paradoxical facets of PTSD and their particular influences over pain perception seem to reinforce the coexistence of PTSD and chronic pain, and should be considered when treating traumatized individuals. This article provides new information regarding the underlying mechanism of the coexistence of PTSD and chronic pain. This knowledge could help to provide better management of PTSD and chronic pain among individuals in the aftermath of trauma. Copyright © 2015 American Pain Society. Published by Elsevier Inc. All rights reserved.

Experimental joint weak measurement on a photon pair as a probe of Hardy's paradox.

PubMed

Lundeen, J S; Steinberg, A M

2009-01-16

It has been proposed that the ability to perform joint weak measurements on postselected systems would allow us to study quantum paradoxes. These measurements can investigate the history of those particles that contribute to the paradoxical outcome. Here we experimentally perform weak measurements of joint (i.e., nonlocal) observables. In an implementation of Hardy's paradox, we weakly measure the locations of two photons, the subject of the conflicting statements behind the paradox. Remarkably, the resulting weak probabilities verify all of these statements but, at the same time, resolve the paradox.

Design principles of paradoxical signaling in the immune system

NASA Astrophysics Data System (ADS)

Hart, Yuval

A widespread feature of cell-cell signaling systems is paradoxical pleiotropy: the same secreted signaling molecule can induce opposite effects in the responding cells. For example, the cytokine IL-2 can promote proliferation and death of T-cells. The role of such paradoxical signaling remains unclear. We suggest that this mechanism provides homeostatic concentration of cells, independent of initial conditions. The crux of the paradoxical mechanism is the combination of a positive and a negative feedback loops creating two stable states - an OFF state and an ON state. Experimentally, we found that CD4 + cells grown in culture with a 30-fold difference in initial concentrations reached a homeostatic concentration nearly independent of initial cell levels (ON-state). Below an initial threshold, cell density decayed to extinction (OFF-state). Mathematical modeling explained the observed cell and cytokine dynamics and predicted conditions that shifted cell fate from homeostasis to the OFF-state. We suggest that paradoxical signaling provides cell circuits with specific dynamical features that are robust to environmental perturbations.

Ventromedial medulla inhibitory neuron inactivation induces REM sleep without atonia and REM sleep behavior disorder.

PubMed

Valencia Garcia, Sara; Brischoux, Frédéric; Clément, Olivier; Libourel, Paul-Antoine; Arthaud, Sébastien; Lazarus, Michael; Luppi, Pierre-Hervé; Fort, Patrice

2018-02-05

Despite decades of research, there is a persistent debate regarding the localization of GABA/glycine neurons responsible for hyperpolarizing somatic motoneurons during paradoxical (or REM) sleep (PS), resulting in the loss of muscle tone during this sleep state. Combining complementary neuroanatomical approaches in rats, we first show that these inhibitory neurons are localized within the ventromedial medulla (vmM) rather than within the spinal cord. We then demonstrate their functional role in PS expression through local injections of adeno-associated virus carrying specific short-hairpin RNA in order to chronically impair inhibitory neurotransmission from vmM. After such selective genetic inactivation, rats display PS without atonia associated with abnormal and violent motor activity, concomitant with a small reduction of daily PS quantity. These symptoms closely mimic human REM sleep behavior disorder (RBD), a prodromal parasomnia of synucleinopathies. Our findings demonstrate the crucial role of GABA/glycine inhibitory vmM neurons in muscle atonia during PS and highlight a candidate brain region that can be susceptible to α-synuclein-dependent degeneration in RBD patients.

The paradox of enrichment in phytoplankton by induced competitive interactions

PubMed Central

Tubay, Jerrold M.; Ito, Hiromu; Uehara, Takashi; Kakishima, Satoshi; Morita, Satoru; Togashi, Tatsuya; Tainaka, Kei-ichi; Niraula, Mohan P.; Casareto, Beatriz E.; Suzuki, Yoshimi; Yoshimura, Jin

2013-01-01

The biodiversity loss of phytoplankton with eutrophication has been reported in many aquatic ecosystems, e.g., water pollution and red tides. This phenomenon seems similar, but different from the paradox of enrichment via trophic interactions, e.g., predator-prey systems. We here propose the paradox of enrichment by induced competitive interactions using multiple contact process (a lattice Lotka-Volterra competition model). Simulation results demonstrate how eutrophication invokes more competitions in a competitive ecosystem resulting in the loss of phytoplankton diversity in ecological time. The paradox is enhanced under local interactions, indicating that the limited dispersal of phytoplankton reduces interspecific competition greatly. Thus, the paradox of enrichment appears when eutrophication destroys an ecosystem either by elevated interspecific competition within a trophic level and/or destabilization by trophic interactions. Unless eutrophication due to human activities is ceased, the world's aquatic ecosystems will be at risk. PMID:24089056

DDT and Malaria Prevention: Addressing the Paradox

PubMed Central

Bouwman, Hindrik; van den Berg, Henk; Kylin, Henrik

2011-01-01

Background The debate regarding dichlorodiphenyltrichloroethane (DDT) in malaria prevention and human health is polarized and can be classified into three positions: anti-DDT, centrist-DDT, pro-DDT. Objective We attempted to arrive at a synthesis by matching a series of questions on the use of DDT for indoor residual spraying (IRS) with literature and insights, and to identify options and opportunities. Discussion Overall, community health is significantly improved through all available malaria control measures, which include IRS with DDT. Is DDT “good”? Yes, because it has saved many lives. Is DDT safe as used in IRS? Recent publications have increasingly raised concerns about the health implications of DDT. Therefore, an unqualified statement that DDT used in IRS is safe is untenable. Are inhabitants and applicators exposed? Yes, and to high levels. Should DDT be used? The fact that DDT is “good” because it saves lives, and “not safe” because it has health and environmental consequences, raises ethical issues. The evidence of adverse human health effects due to DDT is mounting. However, under certain circumstances, malaria control using DDT cannot yet be halted. Therefore, the continued use of DDT poses a paradox recognized by a centrist-DDT position. At the very least, it is now time to invoke precaution. Precautionary actions could include use and exposure reduction. Conclusions There are situations where DDT will provide the best achievable health benefit, but maintaining that DDT is safe ignores the cumulative indications of many studies. In such situations, addressing the paradox from a centrist-DDT position and invoking precaution will help design choices for healthier lives. PMID:21245017

Control of neuronal polarity and plasticity--a renaissance for microtubules?

PubMed

Hoogenraad, Casper C; Bradke, Frank

2009-12-01

Microtubules have been regarded as essential structures for stable neuronal morphology but new studies are highlighting their role in dynamic neuronal processes. Recent work demonstrates that the microtubule cytoskeleton has an active role during different phases of neuronal polarization - microtubules and their stability determine axon formation, they maintain the identity of axons and they regulate the dynamics of dendritic spines, the major sites of excitatory synaptic input. Although microtubules fulfill distinct cellular functions at different developmental stages, the underlying molecular mechanisms are remarkably similar. Reccurring themes are that microtubules direct specific membrane traffic and affect actin dynamics to locally organize axon growth and spine dynamics. We review the novel role of microtubules during neuronal development and discuss models for microtubule-dependent signaling in neuronal plasticity.

How Managers Use the Stockdale Paradox to Balance "the Now and the Next"

ERIC Educational Resources Information Center

Von Bergen, C. W.; Bressler, Martin S.

2017-01-01

Recent discussions of leadership paradoxes have suggested that managers who can hold seemingly opposed, yet interrelated perspectives, are more adaptive and effective. One such paradox that has received relatively little attention is the "Stockdale Paradox," named after Admiral James Stockdale, an American naval officer who was held…

Cav1.3 channels control D2-autoreceptor responses via NCS-1 in substantia nigra dopamine neurons

PubMed Central

Dragicevic, Elena; Poetschke, Christina; Duda, Johanna; Schlaudraff, Falk; Lammel, Stephan; Schiemann, Julia; Fauler, Michael; Hetzel, Andrea; Watanabe, Masahiko; Lujan, Rafael; Malenka, Robert C.; Striessnig, Joerg

2014-01-01

Dopamine midbrain neurons within the substantia nigra are particularly prone to degeneration in Parkinson’s disease. Their selective loss causes the major motor symptoms of Parkinson’s disease, but the causes for the high vulnerability of SN DA neurons, compared to neighbouring, more resistant ventral tegmental area dopamine neurons, are still unclear. Consequently, there is still no cure available for Parkinson’s disease. Current therapies compensate the progressive loss of dopamine by administering its precursor l-DOPA and/or dopamine D2-receptor agonists. D2-autoreceptors and Cav1.3-containing L-type Ca2+ channels both contribute to Parkinson’s disease pathology. L-type Ca2+ channel blockers protect SN DA neurons from degeneration in Parkinson’s disease and its mouse models, and they are in clinical trials for neuroprotective Parkinson’s disease therapy. However, their physiological functions in SN DA neurons remain unclear. D2-autoreceptors tune firing rates and dopamine release of SN DA neurons in a negative feedback loop through activation of G-protein coupled potassium channels (GIRK2, or KCNJ6). Mature SN DA neurons display prominent, non-desensitizing somatodendritic D2-autoreceptor responses that show pronounced desensitization in PARK-gene Parkinson’s disease mouse models. We analysed surviving human SN DA neurons from patients with Parkinson’s disease and from controls, and detected elevated messenger RNA levels of D2-autoreceptors and GIRK2 in Parkinson’s disease. By electrophysiological analysis of postnatal juvenile and adult mouse SN DA neurons in in vitro brain-slices, we observed that D2-autoreceptor desensitization is reduced with postnatal maturation. Furthermore, a transient high-dopamine state in vivo, caused by one injection of either l-DOPA or cocaine, induced adult-like, non-desensitizing D2-autoreceptor responses, selectively in juvenile SN DA neurons, but not ventral tegmental area dopamine neurons. With pharmacological

Cav1.3 channels control D2-autoreceptor responses via NCS-1 in substantia nigra dopamine neurons.

PubMed

Dragicevic, Elena; Poetschke, Christina; Duda, Johanna; Schlaudraff, Falk; Lammel, Stephan; Schiemann, Julia; Fauler, Michael; Hetzel, Andrea; Watanabe, Masahiko; Lujan, Rafael; Malenka, Robert C; Striessnig, Joerg; Liss, Birgit

2014-08-01

Dopamine midbrain neurons within the substantia nigra are particularly prone to degeneration in Parkinson's disease. Their selective loss causes the major motor symptoms of Parkinson's disease, but the causes for the high vulnerability of SN DA neurons, compared to neighbouring, more resistant ventral tegmental area dopamine neurons, are still unclear. Consequently, there is still no cure available for Parkinson's disease. Current therapies compensate the progressive loss of dopamine by administering its precursor l-DOPA and/or dopamine D2-receptor agonists. D2-autoreceptors and Cav1.3-containing L-type Ca(2+) channels both contribute to Parkinson's disease pathology. L-type Ca(2+) channel blockers protect SN DA neurons from degeneration in Parkinson's disease and its mouse models, and they are in clinical trials for neuroprotective Parkinson's disease therapy. However, their physiological functions in SN DA neurons remain unclear. D2-autoreceptors tune firing rates and dopamine release of SN DA neurons in a negative feedback loop through activation of G-protein coupled potassium channels (GIRK2, or KCNJ6). Mature SN DA neurons display prominent, non-desensitizing somatodendritic D2-autoreceptor responses that show pronounced desensitization in PARK-gene Parkinson's disease mouse models. We analysed surviving human SN DA neurons from patients with Parkinson's disease and from controls, and detected elevated messenger RNA levels of D2-autoreceptors and GIRK2 in Parkinson's disease. By electrophysiological analysis of postnatal juvenile and adult mouse SN DA neurons in in vitro brain-slices, we observed that D2-autoreceptor desensitization is reduced with postnatal maturation. Furthermore, a transient high-dopamine state in vivo, caused by one injection of either l-DOPA or cocaine, induced adult-like, non-desensitizing D2-autoreceptor responses, selectively in juvenile SN DA neurons, but not ventral tegmental area dopamine neurons. With pharmacological and genetic

Hindbrain Catecholamine Neurons Activate Orexin Neurons During Systemic Glucoprivation in Male Rats.

PubMed

Li, Ai-Jun; Wang, Qing; Elsarelli, Megan M; Brown, R Lane; Ritter, Sue

2015-08-01

Hindbrain catecholamine neurons are required for elicitation of feeding responses to glucose deficit, but the forebrain circuitry required for these responses is incompletely understood. Here we examined interactions of catecholamine and orexin neurons in eliciting glucoprivic feeding. Orexin neurons, located in the perifornical lateral hypothalamus (PeFLH), are heavily innervated by hindbrain catecholamine neurons, stimulate food intake, and increase arousal and behavioral activation. Orexin neurons may therefore contribute importantly to appetitive responses, such as food seeking, during glucoprivation. Retrograde tracing results showed that nearly all innervation of the PeFLH from the hindbrain originated from catecholamine neurons and some raphe nuclei. Results also suggested that many catecholamine neurons project collaterally to the PeFLH and paraventricular hypothalamic nucleus. Systemic administration of the antiglycolytic agent, 2-deoxy-D-glucose, increased food intake and c-Fos expression in orexin neurons. Both responses were eliminated by a lesion of catecholamine neurons innervating orexin neurons using the retrogradely transported immunotoxin, anti-dopamine-β-hydroxylase saporin, which is specifically internalized by dopamine-β-hydroxylase-expressing catecholamine neurons. Using designer receptors exclusively activated by designer drugs in transgenic rats expressing Cre recombinase under the control of tyrosine hydroxylase promoter, catecholamine neurons in cell groups A1 and C1 of the ventrolateral medulla were activated selectively by peripheral injection of clozapine-N-oxide. Clozapine-N-oxide injection increased food intake and c-Fos expression in PeFLH orexin neurons as well as in paraventricular hypothalamic nucleus neurons. In summary, catecholamine neurons are required for the activation of orexin neurons during glucoprivation. Activation of orexin neurons may contribute to appetitive responses required for glucoprivic feeding.

The paradox of control: An ethnographic analysis of opiate maintenance treatment in a Norwegian prison.

PubMed

Mjåland, Kristian

2015-08-01

Opiate maintenance treatment (OMT) is increasingly being offered in prisons throughout Europe. The benefits of OMT in prison have been found to be similar to those produced by OMT in community settings. However, prison-based OMT has been a controversial issue because of fear of the diversion of OMT medications and the development of black markets for prescription drugs such as buprenorphine and methadone. Prison-based OMT thus involves a delicate balance between the considerations of control and treatment. This article reports on an ethnographic study of a prison-based OMT programme in a closed Norwegian prison. The data include field notes from eight months of participant observation in the prison as well as qualitative interviews with 23 prisoners and 12 prison staff. Midway through the fieldwork, the prison authorities established a separate unit for OMT-enrolled prisoners to reduce the widespread diversion of buprenorphine. This "natural experiment" is explored in the analysis. The prison-based OMT programme was characterised by strict and repressive control to prevent the diversion of buprenorphine, and the control became even stricter after the establishment of the OMT unit. However, the diversion of buprenorphine increased rather than decreased after the establishment of the OMT unit. To understand this "paradox of control", the article engages with theories of legitimacy, power and resistance. The excessive and repressive control was perceived as illegitimate and unfair by the majority of study participants. In various ways, many prisoners protested, confronted and subverted the OMT programme. The increase in buprenorphine diversion is interpreted as a form of collective resistance towards the perceived unfairness of the OMT programme. The article demonstrates that an unbalanced and control-dominated approach to prison-based OMT may have the opposite effect of what is intended. Copyright © 2015 The Author. Published by Elsevier B.V. All rights reserved.

Neurons other than motor neurons in motor neuron disease.

PubMed

Ruffoli, Riccardo; Biagioni, Francesca; Busceti, Carla L; Gaglione, Anderson; Ryskalin, Larisa; Gambardella, Stefano; Frati, Alessandro; Fornai, Francesco

2017-11-01

Amyotrophic lateral sclerosis (ALS) is typically defined by a loss of motor neurons in the central nervous system. Accordingly, morphological analysis for decades considered motor neurons (in the cortex, brainstem and spinal cord) as the neuronal population selectively involved in ALS. Similarly, this was considered the pathological marker to score disease severity ex vivo both in patients and experimental models. However, the concept of non-autonomous motor neuron death was used recently to indicate the need for additional cell types to produce motor neuron death in ALS. This means that motor neuron loss occurs only when they are connected with other cell types. This concept originally emphasized the need for resident glia as well as non-resident inflammatory cells. Nowadays, the additional role of neurons other than motor neurons emerged in the scenario to induce non-autonomous motor neuron death. In fact, in ALS neurons diverse from motor neurons are involved. These cells play multiple roles in ALS: (i) they participate in the chain of events to produce motor neuron loss; (ii) they may even degenerate more than and before motor neurons. In the present manuscript evidence about multi-neuronal involvement in ALS patients and experimental models is discussed. Specific sub-classes of neurons in the whole spinal cord are reported either to degenerate or to trigger neuronal degeneration, thus portraying ALS as a whole spinal cord disorder rather than a disease affecting motor neurons solely. This is associated with a novel concept in motor neuron disease which recruits abnormal mechanisms of cell to cell communication.

Solution of Supplee's submarine paradox through special and general relativity

NASA Astrophysics Data System (ADS)

Vieira, R. S.

2016-12-01

In 1989 Supplee described an apparent relativistic paradox on which a submarine seems to sink to observers at rest within the ocean, but it rather seems to float in the submarine proper frame. In this letter, we show that the paradox arises from a misuse of the Archimedes principle in the relativistic case. Considering first the special relativity, we show that any relativistic force field can be written in the Lorentz form, so that it can always be decomposed into a static (electric-like) and a dynamic (magnetic-like) part. These gravitomagnetic effects provide a relativistic formulation of Archimedes principle, from which the paradox is explained. Besides, if the curved spacetime on the vicinity of the Earth is taken into account, we show that the gravitational force exerted by the Earth on a moving body must increase with the speed of the body. The submarine paradox is then analyzed again with this speed-dependent gravitational force.

The ethical use of paradoxical interventions in psychotherapy.

PubMed Central

Foreman, D M

1990-01-01

The purpose of this paper is to establish ethical guidelines for the use of paradoxical interventions in psychotherapy. These are defined as interventions which are counterintuitive, coercive, and which require non-observance by the client. Arguments are developed to show that such interventions are associated with a psychology that understands individuals solely in terms of their relationship: a 'strong interactionist' position. Ethical principles consistent with such a position are considered, and from these it is derived that: paradox is an ethical technique with resistive patients; it requires consent; its content should be consistent with general ethical principles, especially those of beneficence and non-maleficence; non-paradoxical techniques should be preferred when possible; and it should not be used as an assessment procedure. It is concluded that research is needed to explore the effect of such ethical guidelines of effectiveness, though preliminary impressions are encouraging. PMID:2287016

The paradox of enrichment in an adaptive world

PubMed Central

Mougi, Akihiko; Nishimura, Kinya

2008-01-01

Paradoxically, enrichment can destabilize a predator–prey food web. While adaptive dynamics can greatly influence the stability of interaction systems, few theoretical studies have examined the effect of the adaptive dynamics of interaction-related traits on the possibility of resolution of the paradox of enrichment. We consider the evolution of attack and defence traits of a predator and two prey species in a one predator–two prey system in which the predator practises optimal diet use. The results showed that optimal foraging alone cannot eliminate a pattern of destabilization with enrichment, but trait evolution of the predator or prey can change the pattern to one of stabilization, implying a possible resolution of the paradox of enrichment. Furthermore, trait evolution in all species can broaden the parameter range of stabilization. Importantly, rapid evolution can stabilize this system, but weaken its stability in the face of enrichment. PMID:18700201

On Johnson's Paradox: Hypothesis Verification

ERIC Educational Resources Information Center

Noble, Clyde E.

1975-01-01

When H. M. Johnson argued that all inductive reasoning is based on the fallacy of affirming the consequent and cannot therefore establish the 'truth' of scientific hypotheses, he posed a paradox for strict empiricists. Author examined Johnson's argument. (Editor/RK)

The Bohr paradox

NASA Astrophysics Data System (ADS)

Crease, Robert P.

2008-05-01

In his book Niels Bohr's Times, the physicist Abraham Pais captures a paradox in his subject's legacy by quoting three conflicting assessments. Pais cites Max Born, of the first generation of quantum physics, and Werner Heisenberg, of the second, as saying that Bohr had a greater influence on physics and physicists than any other scientist. Yet Pais also reports a distinguished younger colleague asking with puzzlement and scepticism "What did Bohr really do?".

The mean, the median, and the St. Petersburg paradox.

PubMed

Hayden, Benjamin Y; Platt, Michael L

2009-06-01

The St. Petersburg Paradox is a famous economic and philosophical puzzle that has generated numerous conflicting explanations. To shed empirical light on this phenomenon, we examined subjects' bids for one St. Petersburg gamble with a real monetary payment. We found that bids were typically lower than twice the smallest payoff, and thus much lower than is generally supposed. We also examined bids offered for several hypothetical variants of the St. Petersburg Paradox. We found that bids were weakly affected by truncating the gamble, were strongly affected by repeats of the gamble, and depended linearly on the initial "seed" value of the gamble. One explanation, which we call the median heuristic , strongly predicts these data. Subjects following this strategy evaluate a gamble as if they were taking the median rather than the mean of the payoff distribution. Finally, we argue that the distribution of outcomes embodied in the St. Petersburg paradox is so divergent from the Gaussian form that the statistical mean is a poor estimator of expected value, so that the expected value of the St. Petersburg gamble is undefined. These results suggest that this classic paradox has a straightforward explanation rooted in the use of a statistical heuristic.

A screen for constituents of motor control and decision making in Drosophila reveals visual distance-estimation neurons

PubMed Central

Triphan, Tilman; Nern, Aljoscha; Roberts, Sonia F.; Korff, Wyatt; Naiman, Daniel Q.; Strauss, Roland

2016-01-01

Climbing over chasms larger than step size is vital to fruit flies, since foraging and mating are achieved while walking. Flies avoid futile climbing attempts by processing parallax-motion vision to estimate gap width. To identify neuronal substrates of climbing control, we screened a large collection of fly lines with temporarily inactivated neuronal populations in a novel high-throughput assay described here. The observed climbing phenotypes were classified; lines in each group are reported. Selected lines were further analysed by high-resolution video cinematography. One striking class of flies attempts to climb chasms of unsurmountable width; expression analysis guided us to C2 optic-lobe interneurons. Inactivation of C2 or the closely related C3 neurons with highly specific intersectional driver lines consistently reproduced hyperactive climbing whereas strong or weak artificial depolarization of C2/C3 neurons strongly or mildly decreased climbing frequency. Contrast-manipulation experiments support our conclusion that C2/C3 neurons are part of the distance-evaluation system. PMID:27255169

Paramagnetism Paradoxes: Projectable Demonstrations

ERIC Educational Resources Information Center

Sauls, Frederick C.; Vitz, Ed

2008-01-01

Drops of oil in Mn(SO[subscript 4])(aq) and drops of the solution in oil show opposite effects when brought near a rare earth magnet. Oxygen, nitrogen, and air bubbles atop water show expected attraction, repulsion, and null behavior, respectively. Air bubbles atop aqueous Mn(SO[subscript 4]) show paradoxical behavior because the magnet's…

Paradoxes of the Presidency.

ERIC Educational Resources Information Center

Perlman, Daniel H.

1989-01-01

The many paradoxes of the profession of the college president are discussed, with focus on whether the presidency is a profession to which a person should aspire and can prepare. Some people feel the position of presidency should only be filled by people with a love of scholarship and the intellectual life. The expectation, especially at the more…

Behind the Mpemba paradox

PubMed Central

Sun, Chang Qing

2015-01-01

Mpemba paradox results from hydrogen-bond anomalous relaxation. Heating stretches the O:H nonbond and shortens the H‒O bond via Coulomb coupling; cooling reverses this process to emit heat at a rate depending on its initial storage. Skin ultra-low mass density raises the thermal diffusivity and favors outward heat flow from the liquid. PMID:27227000

A Hydrostatic Paradox Revisited

ERIC Educational Resources Information Center

Ganci, Salvatore

2012-01-01

This paper revisits a well-known hydrostatic paradox, observed when turning upside down a glass partially filled with water and covered with a sheet of light material. The phenomenon is studied in its most general form by including the mass of the cover. A historical survey of this experiment shows that a common misunderstanding of the phenomenon…

Obesity paradox in patients undergoing coronary intervention: A review

PubMed Central

Patel, Nirav; Elsaid, Ossama; Shenoy, Abhishek; Sharma, Abhishek; McFarlane, Samy I

2017-01-01

There is strong relationship exist between obesity and cardiovascular disease including coronary artery disease (CAD). However, better outcomes noted in obese patients undergoing percutaneous cardiovascular interventions for CAD, a phenomenon known as the obesity paradox. In this review, we performed extensive search for obesity paradox in obese patients undergoing percutaneous coronary intervention and discussed possible mechanism and disparities in different race and sex. PMID:29081905

Paradoxical Personality and Academic Achievement in College Students From Buenos Aires

PubMed Central

Freiberg Hoffmann, Agustín; Fernández Liporace, María Mercedes

2015-01-01

This paper presents a study on paradoxical personality, defined as a distinctive feature in creative persons, developed with 350 college students from Buenos Aires. Goals aimed at describing and analysing possible significant differences of paradoxical traits in students from diverse majors representing seven different fields of study, and examining the relationship between each bipolar trait and academic achievement. The sample was composed of 7 groups (n = 50 by group) representing fields of study typically offered in public universities, Biology, Computer Science, Engineering, Law, Nutrition, Psychology, and History of Art. Analyses by career provided descriptive information about students of these majors, concerning their paradoxical personality profiles. Correlational studies verified significant associations between academic achievement and most paradoxical traits in majors such as Computer Science, Nutrition and Psychology. Results are discussed regarding practical outcomes and teaching programs. PMID:27247680

Paradoxical self-esteem and selectivity in the processing of social information.

PubMed

Tafarodi, R W

1998-05-01

Paradoxical self-esteem is defined as contrasting levels of self-liking and self-competence. Consideration of the social and motivational implications of this uncommon form of self-esteem suggests that heightened selectivity in the processing of social information may be behind its persistence. Two experiments were conducted to confirm the prediction of heightened selectivity in paradoxicals. As expected, those paradoxically low in self-liking were more negatively biased in their memory for personality feedback (Study 1) and interpretation of valuatively ambiguous phrases (Study 2) than were their counterparts who shared the same low self-liking but were also low in self-competence. Symmetrical with this result, those paradoxically high in self-liking exhibited a heightened positive bias relative to those who were high in both self-liking and self-competence. The findings are discussed in relation to attitudes and motivation.

Development of a bench-top device for parallel climate-controlled recordings of neuronal cultures activity with microelectrode arrays.

PubMed

Regalia, Giulia; Biffi, Emilia; Achilli, Silvia; Ferrigno, Giancarlo; Menegon, Andrea; Pedrocchi, Alessandra

2016-02-01

Two binding requirements for in vitro studies on long-term neuronal networks dynamics are (i) finely controlled environmental conditions to keep neuronal cultures viable and provide reliable data for more than a few hours and (ii) parallel operation on multiple neuronal cultures to shorten experimental time scales and enhance data reproducibility. In order to fulfill these needs with a Microelectrode Arrays (MEA)-based system, we designed a stand-alone device that permits to uninterruptedly monitor neuronal cultures activity over long periods, overcoming drawbacks of existing MEA platforms. We integrated in a single device: (i) a closed chamber housing four MEAs equipped with access for chemical manipulations, (ii) environmental control systems and embedded sensors to reproduce and remotely monitor the standard in vitro culture environment on the lab bench (i.e. in terms of temperature, air CO2 and relative humidity), and (iii) a modular MEA interface analog front-end for reliable and parallel recordings. The system has been proven to assure environmental conditions stable, physiological and homogeneos across different cultures. Prolonged recordings (up to 10 days) of spontaneous and pharmacologically stimulated neuronal culture activity have not shown signs of rundown thanks to the environmental stability and have not required to withdraw the cells from the chamber for culture medium manipulations. This system represents an effective MEA-based solution to elucidate neuronal network phenomena with slow dynamics, such as long-term plasticity, effects of chronic pharmacological stimulations or late-onset pathological mechanisms. © 2015 Wiley Periodicals, Inc.

A history of the Allais paradox.

PubMed

Heukelom, Floris

2015-03-01

This article documents the history of the Allais paradox, and shows that underneath the many discussions of the various protagonists lay different, irreconcilable epistemological positions. Savage, like his mentor von Neumann and similar to economist Friedman, worked from an epistemology of generalized characterizations. Allais, on the other hand, like economists Samuelson and Baumol, started from an epistemology of exact descriptions in which every axiom was an empirical claim that could be refuted directly by observations. As a result, the two sides failed to find a common ground. Only a few decades later was the now so-called Allais paradox rediscovered as an important precursor when a new behavioural economic subdiscipline started to adopt the epistemology of exact descriptions and its accompanying falsifications of rational choice theory.

Control of axonal sprouting and dendrite branching by the Nrg-Ank complex at the neuron-glia interface.

PubMed

Yamamoto, Misato; Ueda, Ryu; Takahashi, Kuniaki; Saigo, Kaoru; Uemura, Tadashi

2006-08-22

Neurons are highly polarized cells with distinct subcellular compartments, including dendritic arbors and an axon. The proper function of the nervous system relies not only on correct targeting of axons, but also on development of neuronal-class-specific geometry of dendritic arbors [1-4]. To study the intercellular control of the shaping of dendritic trees in vivo, we searched for cell-surface proteins expressed by Drosophila dendritic arborization (da) neurons [5-7]. One of them was Neuroglian (Nrg), a member of the Ig superfamily ; Nrg and vertebrate L1-family molecules have been implicated in various aspects of neuronal wiring, such as axon guidance, axonal myelination, and synapse formation [9-12]. A subset of the da neurons in nrg mutant embryos exhibited deformed dendritic arbors and abnormal axonal sprouting. Our functional analysis in a cell-type-selective manner strongly suggested that those da neurons employed Nrg to interact with the peripheral glia for suppressing axonal sprouting and for forming second-order dendritic branches. At least for the former role, Nrg functioned in concert with the intracellular adaptor protein Ankyrin (Ank) [13]. Thus, the neuron-glia interaction that is mediated by Nrg, together with Ank under some situations, contributes to axonal and dendritic morphogenesis.

From induction to conduction: how intrinsic transcriptional priming of extrinsic neuronal connectivity shapes neuronal identity.

PubMed

Russ, Jeffrey B; Kaltschmidt, Julia A

2014-10-01

Every behaviour of an organism relies on an intricate and vastly diverse network of neurons whose identity and connectivity must be specified with extreme precision during development. Intrinsically, specification of neuronal identity depends heavily on the expression of powerful transcription factors that direct numerous features of neuronal identity, including especially properties of neuronal connectivity, such as dendritic morphology, axonal targeting or synaptic specificity, ultimately priming the neuron for incorporation into emerging circuitry. As the neuron's early connectivity is established, extrinsic signals from its pre- and postsynaptic partners feedback on the neuron to further refine its unique characteristics. As a result, disruption of one component of the circuitry during development can have vital consequences for the proper identity specification of its synaptic partners. Recent studies have begun to harness the power of various transcription factors that control neuronal cell fate, including those that specify a neuron's subtype-specific identity, seeking insight for future therapeutic strategies that aim to reconstitute damaged circuitry through neuronal reprogramming.

Killing Mosquitoes and Keeping Practice: Teacher Education as Sustaining Paradox

ERIC Educational Resources Information Center

Keiser, David Lee

2013-01-01

The moral and ethical charge of teaching and teacher education includes sustaining equanimity and paradox, and maintaining poise amongst contradicting policies and interests. This paper draws upon the wisdom of the Tao Te Ching to address some paradoxes in education and teacher preparation. Specifically, the article looks at four chapters of the…

Intraspinal serotonergic neurons consist of two, temporally distinct populations in developing zebrafish

PubMed Central

Montgomery, Jacob E.; Wiggin, Timothy D.; Rivera-Perez, Luis M.; Lillesaar, Christina; Masino, Mark A.

2015-01-01

Zebrafish intraspinal serotonergic neuron (ISN) morphology and distribution have been examined in detail at different ages; however, some aspects of the development of these cells remain unclear. Although antibodies to serotonin (5-HT) have detected ISNs in the ventral spinal cord of embryos, larvae, and adults, the only tryptophan hydroxylase (tph) transcript that has been described in the spinal cord is tph1a. Paradoxically, spinal tph1a is expressed transiently in embryos, which brings the source of 5-HT in the ISNs of larvae and adults into question. Because the pet1 and tph2 promoters drive transgene expression in the spinal cord, we hypothesized that tph2 is expressed in spinal cords of zebrafish larvae. We confirmed this hypothesis through in situ hybridization. Next, we used 5-HT antibody labeling and transgenic markers of tph2-expressing neurons to identify a transient population of ISNs in embryos that was distinct from ISNs that appeared later in development. The existence of separate ISN populations may not have been recognized previously due to their shared location in the ventral spinal cord. Finally, we used transgenic markers and immunohistochemical labeling to identify the transient ISN population as GABAergic Kolmer-Agduhr double-prime (KA″) neurons. Altogether, this study revealed a novel developmental paradigm in which KA″ neurons are transiently serotonergic before the appearance of a stable population of tph2-expressing ISNs. PMID:26437856

Short-chain fatty acids regulate the enteric neurons and control gastrointestinal motility in rats.

PubMed

Soret, Rodolphe; Chevalier, Julien; De Coppet, Pierre; Poupeau, Guillaume; Derkinderen, Pascal; Segain, Jean Pierre; Neunlist, Michel

2010-05-01

Little is known about the environmental and nutritional regulation of the enteric nervous system (ENS), which controls gastrointestinal motility. Short-chain fatty acids (SCFAs) such as butyrate regulate colonic mucosa homeostasis and can modulate neuronal excitability. We investigated their effects on the ENS and colonic motility. Effects of butyrate on the ENS were studied in colons of rats given a resistant starch diet (RSD) or intracecal perfusion of SCFAs. Effects of butyrate were also studied in primary cultures of ENS. The neurochemical phenotype of the ENS was analyzed with antibodies against Hu, choline acetyltransferase (ChAT), and neuronal nitric oxide synthase (nNOS) and by quantitative polymerase chain reaction. Signaling pathways involved were analyzed by pharmacologic and molecular biology methods. Colonic motility was assessed in vivo and ex vivo. In vivo and in vitro, RSD and butyrate significantly increased the proportion of ChAT- but not nNOS-immunoreactive myenteric neurons. Acetate and propionate did not reproduce the effects of butyrate. Enteric neurons expressed monocarboxylate transporter 2 (MCT2). Small interfering RNAs silenced MCT2 and prevented the increase in the proportion of ChAT- immunoreactive neurons induced by butyrate. Butyrate and trichostatin A increased histone H3 acetylation in enteric neurons. Effects of butyrate were prevented by inhibitors of the Src signaling pathway. RSD increased colonic transit, and butyrate increased the cholinergic-mediated colonic circular muscle contractile response ex vivo. Butyrate or histone deacetylase inhibitors might be used, along with nutritional approaches, to treat various gastrointestinal motility disorders associated with inhibition of colonic transit. Copyright 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.

Paradoxical consequences of prohibitions.

PubMed

Sheikh, Sana; Janoff-Bulman, Ronnie

2013-08-01

Explanations based in attribution theory claim that strong external controls such as parental restrictiveness and punishment undermine moral internalization. In contrast, 3 studies provide evidence that parental punishment does socialize morality, but of a particular sort: a morality focused on prohibitions (i.e., proscriptive orientation) rather than positive obligations (i.e., prescriptive orientation). Study 1 found young adults' accounts of parental restrictiveness and punishment activated their sensitivity to prohibitions and predicted a proscriptive orientation. Consistent with the greater potency of temptations for proscriptively oriented children, as well as past research linking shame to proscriptive morality, Study 2 found that restrictive parenting was also associated with greater suppression of temptations. Finally, Studies 3A and 3B found that suppressing these immoral thoughts is paradoxically harder for those with strong proscriptive orientations; more specifically, priming a proscriptive (versus prescriptive) orientation and inducing mental suppression of "immoral" thoughts led to the most ego depletion for those with restrictive parents. Overall, individuals who had restrictive parents had the lowest self-regulatory ability to resist their "immoral" temptations after prohibitions were activated. In contrast to common attributional explanations, these studies suggest that harsh external control by parents does not undercut moral socialization but rather undermines individuals' ability to resist temptation.

Cerebellar Nuclear Neurons Use Time and Rate Coding to Transmit Purkinje Neuron Pauses.

PubMed

Sudhakar, Shyam Kumar; Torben-Nielsen, Benjamin; De Schutter, Erik

2015-12-01

Neurons of the cerebellar nuclei convey the final output of the cerebellum to their targets in various parts of the brain. Within the cerebellum their direct upstream connections originate from inhibitory Purkinje neurons. Purkinje neurons have a complex firing pattern of regular spikes interrupted by intermittent pauses of variable length. How can the cerebellar nucleus process this complex input pattern? In this modeling study, we investigate different forms of Purkinje neuron simple spike pause synchrony and its influence on candidate coding strategies in the cerebellar nuclei. That is, we investigate how different alignments of synchronous pauses in synthetic Purkinje neuron spike trains affect either time-locking or rate-changes in the downstream nuclei. We find that Purkinje neuron synchrony is mainly represented by changes in the firing rate of cerebellar nuclei neurons. Pause beginning synchronization produced a unique effect on nuclei neuron firing, while the effect of pause ending and pause overlapping synchronization could not be distinguished from each other. Pause beginning synchronization produced better time-locking of nuclear neurons for short length pauses. We also characterize the effect of pause length and spike jitter on the nuclear neuron firing. Additionally, we find that the rate of rebound responses in nuclear neurons after a synchronous pause is controlled by the firing rate of Purkinje neurons preceding it.

Desynchronization in an ensemble of globally coupled chaotic bursting neuronal oscillators by dynamic delayed feedback control

NASA Astrophysics Data System (ADS)

Che, Yanqiu; Yang, Tingting; Li, Ruixue; Li, Huiyan; Han, Chunxiao; Wang, Jiang; Wei, Xile

2015-09-01

In this paper, we propose a dynamic delayed feedback control approach or desynchronization of chaotic-bursting synchronous activities in an ensemble of globally coupled neuronal oscillators. We demonstrate that the difference signal between an ensemble's mean field and its time delayed state, filtered and fed back to the ensemble, can suppress the self-synchronization in the ensemble. These individual units are decoupled and stabilized at the desired desynchronized states while the stimulation signal reduces to the noise level. The effectiveness of the method is illustrated by examples of two different populations of globally coupled chaotic-bursting neurons. The proposed method has potential for mild, effective and demand-controlled therapy of neurological diseases characterized by pathological synchronization.

Brownian motion and gambling: from ratchets to paradoxical games

NASA Astrophysics Data System (ADS)

Parrondo, J. M. R.; Dinís, Luis

2004-02-01

Two losing gambling games, when alternated in a periodic or random fashion, can produce a winning game. This paradox has been inspired by certain physical systems capable of rectifying fluctuations: the so-called Brownian ratchets. In this paper we review this paradox, from Brownian ratchets to the most recent studies on collective games, providing some intuitive explanations of the unexpected phenomena that we will find along the way.

Two Paradoxes of the "Seller's Market" of Chinese Higher Education

ERIC Educational Resources Information Center

Huang, J.

2005-01-01

In recent years, two "paradoxes" have emerged in the "seller's market" of Chinese higher education. One is a strong demand for buying educational services and a weak demand for consumption; a second is the coexistence of an entry to the seller's market and an exit point from the buyer's market. These two "paradoxes"…

Scientific progress despite irreproducibility: A seeming paradox

PubMed Central

Shiffrin, Richard M.; Stigler, Stephen M.

2018-01-01

It appears paradoxical that science is producing outstanding new results and theories at a rapid rate at the same time that researchers are identifying serious problems in the practice of science that cause many reports to be irreproducible and invalid. Certainly, the practice of science needs to be improved, and scientists are now pursuing this goal. However, in this perspective, we argue that this seeming paradox is not new, has always been part of the way science works, and likely will remain so. We first introduce the paradox. We then review a wide range of challenges that appear to make scientific success difficult. Next, we describe the factors that make science work—in the past, present, and presumably also in the future. We then suggest that remedies for the present practice of science need to be applied selectively so as not to slow progress and illustrate with a few examples. We conclude with arguments that communication of science needs to emphasize not just problems but the enormous successes and benefits that science has brought and is now bringing to all elements of modern society. PMID:29531095

Leptin Acts via Lateral Hypothalamic Area Neurotensin Neurons to Inhibit Orexin Neurons by Multiple GABA-Independent Mechanisms

PubMed Central

Goforth, Paulette B.; Leinninger, Gina M.; Patterson, Christa M.

2014-01-01

The adipocyte-derived hormone leptin modulates neural systems appropriately for the status of body energy stores. Leptin inhibits lateral hypothalamic area (LHA) orexin (OX; also known as hypocretin)-producing neurons, which control feeding, activity, and energy expenditure, among other parameters. Our previous results suggest that GABAergic LHA leptin receptor (LepRb)-containing and neurotensin (Nts)-containing (LepRbNts) neurons lie in close apposition with OX neurons and control Ox mRNA expression. Here, we show that, similar to leptin, activation of LHA Nts neurons by the excitatory hM3Dq DREADD (designer receptor exclusively activated by designer drugs) hyperpolarizes membrane potential and suppresses action potential firing in OX neurons in mouse hypothalamic slices. Furthermore, ablation of LepRb from Nts neurons abrogated the leptin-mediated inhibition, demonstrating that LepRbNts neurons mediate the inhibition of OX neurons by leptin. Leptin did not significantly enhance GABAA-mediated inhibitory synaptic transmission, and GABA receptor antagonists did not block leptin-mediated inhibition of OX neuron activity. Rather, leptin diminished the frequency of spontaneous EPSCs onto OX neurons. Furthermore, leptin indirectly activated an ATP-sensitive potassium (KATP) channel in OX neurons, which was required for the hyperpolarization of OX neurons by leptin. Although Nts did not alter OX activity, galanin, which is coexpressed in LepRbNts neurons, inhibited OX neurons, whereas the galanin receptor antagonist M40 (galanin-(1–12)-Pro3-(Ala-Leu)2-Ala amide) prevented the leptin-induced hyperpolarization of OX cells. These findings demonstrate that leptin indirectly inhibits OX neurons by acting on LHA LepRbNts neurons to mediate two distinct GABA-independent mechanisms of inhibition: the presynaptic inhibition of excitatory neurotransmission and the opening of KATP channels. PMID:25143620

Leptin acts via lateral hypothalamic area neurotensin neurons to inhibit orexin neurons by multiple GABA-independent mechanisms.

PubMed

Goforth, Paulette B; Leinninger, Gina M; Patterson, Christa M; Satin, Leslie S; Myers, Martin G

2014-08-20

The adipocyte-derived hormone leptin modulates neural systems appropriately for the status of body energy stores. Leptin inhibits lateral hypothalamic area (LHA) orexin (OX; also known as hypocretin)-producing neurons, which control feeding, activity, and energy expenditure, among other parameters. Our previous results suggest that GABAergic LHA leptin receptor (LepRb)-containing and neurotensin (Nts)-containing (LepRb(Nts)) neurons lie in close apposition with OX neurons and control Ox mRNA expression. Here, we show that, similar to leptin, activation of LHA Nts neurons by the excitatory hM3Dq DREADD (designer receptor exclusively activated by designer drugs) hyperpolarizes membrane potential and suppresses action potential firing in OX neurons in mouse hypothalamic slices. Furthermore, ablation of LepRb from Nts neurons abrogated the leptin-mediated inhibition, demonstrating that LepRb(Nts) neurons mediate the inhibition of OX neurons by leptin. Leptin did not significantly enhance GABAA-mediated inhibitory synaptic transmission, and GABA receptor antagonists did not block leptin-mediated inhibition of OX neuron activity. Rather, leptin diminished the frequency of spontaneous EPSCs onto OX neurons. Furthermore, leptin indirectly activated an ATP-sensitive potassium (K(ATP)) channel in OX neurons, which was required for the hyperpolarization of OX neurons by leptin. Although Nts did not alter OX activity, galanin, which is coexpressed in LepRb(Nts) neurons, inhibited OX neurons, whereas the galanin receptor antagonist M40 (galanin-(1-12)-Pro3-(Ala-Leu)2-Ala amide) prevented the leptin-induced hyperpolarization of OX cells. These findings demonstrate that leptin indirectly inhibits OX neurons by acting on LHA LepRb(Nts) neurons to mediate two distinct GABA-independent mechanisms of inhibition: the presynaptic inhibition of excitatory neurotransmission and the opening of K(ATP) channels. Copyright © 2014 the authors 0270-6474/14/3411405-11$15.00/0.

Paradoxical articular manifestations in patients with inflammatory bowel diseases treated with infliximab.

PubMed

Thiebault, Henri; Boyard-Lasselin, Pauline; Guignant, Caroline; Guillaume, Nicolas; Wacrenier, Adrien; Sabbagh, Charles; Rebibo, Lionel; Brazier, Franck; Meynier, Jonathan; Nguyen-Khac, Eric; Dupas, Jean-Louis; Goëb, Vincent; Fumery, Mathurin

2016-08-01

Articular involvement is the most common extraintestinal manifestation associated with inflammatory bowel diseases (IBDs). Manifestations are 'paradoxical' when they occur during treatment, notably with anti-tumor necrosis factor (anti-TNF) drugs, which are expected to prevent or treat them. The aim of this study was to assess the frequency, characteristics, and associated factors of paradoxical articular manifestations in patients with IBD treated with anti-TNF. In this prospective single-center study, an examination by a rheumatologist was systematically offered to all patients with IBD treated with infliximab (IFX) to assess the prevalence of articular manifestations and distinguish between those related to treatment and those associated with intestinal disease. Paradoxical manifestations were defined as the occurrence of articular manifestations (excluding induced lupus and hypersensitivity reactions) during anti-TNF therapy in patients with intestinal remission. Measures of biological inflammatory, immunological markers, HLA-B27 allele, IFX trough levels, and anti-IFX antibody (Ab) were performed for all patients. Between May 2013 and April 2014, 65 patients with Crohn's disease and 15 with patients ulcerative colitis treated with IFX were included. The median duration of anti-TNF therapy was 66 months [quartile (Q)1=23 months-Q3=81 months]. Articular manifestations were observed in 50 (62%) patients treated with IFX. Eleven percent (n=9) were considered to be associated with IBD and 16% (n=13) to be associated with anti-TNF therapy. Among articular manifestations associated with anti-TNF therapy, nine (11%) patients were considered paradoxical, two (2%) as drug-induced lupus, and two (2%) as a hypersensitivity reaction. Among the nine patients with paradoxical manifestations, all had Crohn's disease in clinical remission, three patients presented a spondyloarthropathy, and three developed associated paradoxical psoriasis. No patient discontinued anti

High-resolution optical control of spatiotemporal neuronal activity patterns in zebrafish using a digital micromirror device.

PubMed

Zhu, Peixin; Fajardo, Otto; Shum, Jennifer; Zhang Schärer, Yan-Ping; Friedrich, Rainer W

2012-06-28

Optogenetic approaches allow the manipulation of neuronal activity patterns in space and time by light, particularly in small animals such as zebrafish. However, most techniques cannot control neuronal activity independently at different locations. Here we describe equipment and provide a protocol for single-photon patterned optical stimulation of neurons using a digital micromirror device (DMD). This method can create arbitrary spatiotemporal light patterns with spatial and temporal resolutions in the micrometer and submillisecond range, respectively. Different options to integrate a DMD into a multiphoton microscope are presented and compared. We also describe an ex vivo preparation of the adult zebrafish head that greatly facilitates optogenetic and other experiments. After assembly, the initial alignment takes about one day and the zebrafish preparation takes <30 min. The method has previously been used to activate channelrhodopsin-2 and manipulate oscillatory synchrony among spatially distributed neurons in the zebrafish olfactory bulb. It can be adapted easily to a wide range of other species, optogenetic probes and scientific applications.

Generalized friendship paradox in complex networks: The case of scientific collaboration

NASA Astrophysics Data System (ADS)

Eom, Young-Ho; Jo, Hang-Hyun

2014-04-01

The friendship paradox states that your friends have on average more friends than you have. Does the paradox ``hold'' for other individual characteristics like income or happiness? To address this question, we generalize the friendship paradox for arbitrary node characteristics in complex networks. By analyzing two coauthorship networks of Physical Review journals and Google Scholar profiles, we find that the generalized friendship paradox (GFP) holds at the individual and network levels for various characteristics, including the number of coauthors, the number of citations, and the number of publications. The origin of the GFP is shown to be rooted in positive correlations between degree and characteristics. As a fruitful application of the GFP, we suggest effective and efficient sampling methods for identifying high characteristic nodes in large-scale networks. Our study on the GFP can shed lights on understanding the interplay between network structure and node characteristics in complex networks.

Wireless Sensor Network Congestion Control Based on Standard Particle Swarm Optimization and Single Neuron PID

PubMed Central

Yang, Xiaoping; Chen, Xueying; Xia, Riting; Qian, Zhihong

2018-01-01

Aiming at the problem of network congestion caused by the large number of data transmissions in wireless routing nodes of wireless sensor network (WSN), this paper puts forward an algorithm based on standard particle swarm–neural PID congestion control (PNPID). Firstly, PID control theory was applied to the queue management of wireless sensor nodes. Then, the self-learning and self-organizing ability of neurons was used to achieve online adjustment of weights to adjust the proportion, integral and differential parameters of the PID controller. Finally, the standard particle swarm optimization to neural PID (NPID) algorithm of initial values of proportion, integral and differential parameters and neuron learning rates were used for online optimization. This paper describes experiments and simulations which show that the PNPID algorithm effectively stabilized queue length near the expected value. At the same time, network performance, such as throughput and packet loss rate, was greatly improved, which alleviated network congestion and improved network QoS. PMID:29671822

Wireless Sensor Network Congestion Control Based on Standard Particle Swarm Optimization and Single Neuron PID.

PubMed

Yang, Xiaoping; Chen, Xueying; Xia, Riting; Qian, Zhihong

2018-04-19

Aiming at the problem of network congestion caused by the large number of data transmissions in wireless routing nodes of wireless sensor network (WSN), this paper puts forward an algorithm based on standard particle swarm⁻neural PID congestion control (PNPID). Firstly, PID control theory was applied to the queue management of wireless sensor nodes. Then, the self-learning and self-organizing ability of neurons was used to achieve online adjustment of weights to adjust the proportion, integral and differential parameters of the PID controller. Finally, the standard particle swarm optimization to neural PID (NPID) algorithm of initial values of proportion, integral and differential parameters and neuron learning rates were used for online optimization. This paper describes experiments and simulations which show that the PNPID algorithm effectively stabilized queue length near the expected value. At the same time, network performance, such as throughput and packet loss rate, was greatly improved, which alleviated network congestion and improved network QoS.

The Paradoxical Signals of Two TrkC Receptor Isoforms Supports a Rationale for Novel Therapeutic Strategies in ALS

PubMed Central

Barcelona, Pablo F.; Galan, Alba; Aboulkassim, Tahar; Teske, Katrina; Rogers, Mary-Louise; Bertram, Lisa; Wang, Jing; Yousefi, Masoud; Rush, Robert; Fabian, Marc; Cashman, Neil

2016-01-01

Full length TrkC (TrkC-FL) is a receptor tyrosine kinase whose mRNA can be spliced to a truncated TrkC.T1 isoform lacking the kinase domain. Neurotrophin-3 (NT-3) activates TrkC-FL to maintain motor neuron health and function and TrkC.T1 to produce neurotoxic TNF-α; hence resulting in opposing pathways. In mouse and human ALS spinal cord, the reduction of miR-128 that destabilizes TrkC.T1 mRNA results in up-regulated TrkC.T1 and TNF-α in astrocytes. We exploited conformational differences to develop an agonistic mAb 2B7 that selectively activates TrkC-FL, to circumvent TrkC.T1 activation. In mouse ALS, 2B7 activates spinal cord TrkC-FL signals, improves spinal cord motor neuron phenotype and function, and significantly prolongs life-span. Our results elucidate biological paradoxes of receptor isoforms and their role in disease progression, validate the concept of selectively targeting conformational epitopes in naturally occurring isoforms, and may guide the development of pro-neuroprotective (TrkC-FL) and anti-neurotoxic (TrkC.T1) therapeutic strategies. PMID:27695040

Arcuate NPY neurons sense and integrate peripheral metabolic signals to control feeding.

PubMed

Kohno, Daisuke; Yada, Toshihiko

2012-12-01

NPY neuron in the hypothalamic arcuate nucleus is a key feeding center. Studies have shown that NPY neuron in the arcuate nucleus has a role to induce food intake. The arcuate nucleus is structurally unique with lacking blood brain barrier. Peripheral energy signals including hormones and nutrition can reach the arcuate nucleus. In this review, we discuss sensing and integrating peripheral signals in NPY neurons. In the arcuate nucleus, ghrelin mainly activates NPY neurons. Leptin and insulin suppress the ghrelin-induced activation in 30-40% of the ghrelin-activated NPY neurons. Lowering glucose concentration activates 40% of NPY neurons. These results indicate that NPY neuron in the arcuate nucleus is a feeding center in which major peripheral energy signals are directly sensed and integrated. Furthermore, there are subpopulations of NPY neurons in regard to their responsiveness to peripheral signals. These findings suggest that NPY neuron in the arcuate nucleus is an essential feeding center to induce food intake in response to peripheral metabolic state. Copyright © 2012 Elsevier Ltd. All rights reserved.

Art's Pedagogical Paradox

ERIC Educational Resources Information Center

Kalin, Nadine M.

2014-01-01

This article contributes to conversations concerning art education futures through engaging alternative relations between art, education, and democracy that mobilize education as art projects associated with the "pedagogical turn" as sites of liminality and paradox. An analysis of the art project, Pedagogical Factory, is used to outline…

Review Essay: Pondering Pedagogical Paradoxes

ERIC Educational Resources Information Center

Spencer, Leland G.

2015-01-01

Herein, Leland Spencer provides a review of four book selections while reflecting on paradoxes regularly faced by feminist teachers (and scholars, activists, and thinkers). The books include: (1) Bradley, Harriet. "Gender." Cambridge: Polity, 2012. Print; (2) Murphy, Michael J., and Elizabeth N. Ribarsky, eds. "Activities for…

Reconstruction of phrenic neuron identity in embryonic stem cell-derived motor neurons

PubMed Central

Machado, Carolina Barcellos; Kanning, Kevin C.; Kreis, Patricia; Stevenson, Danielle; Crossley, Martin; Nowak, Magdalena; Iacovino, Michelina; Kyba, Michael; Chambers, David; Blanc, Eric; Lieberam, Ivo

2014-01-01

Air breathing is an essential motor function for vertebrates living on land. The rhythm that drives breathing is generated within the central nervous system and relayed via specialised subsets of spinal motor neurons to muscles that regulate lung volume. In mammals, a key respiratory muscle is the diaphragm, which is innervated by motor neurons in the phrenic nucleus. Remarkably, relatively little is known about how this crucial subtype of motor neuron is generated during embryogenesis. Here, we used direct differentiation of motor neurons from mouse embryonic stem cells as a tool to identify genes that direct phrenic neuron identity. We find that three determinants, Pou3f1, Hoxa5 and Notch, act in combination to promote a phrenic neuron molecular identity. We show that Notch signalling induces Pou3f1 in developing motor neurons in vitro and in vivo. This suggests that the phrenic neuron lineage is established through a local source of Notch ligand at mid-cervical levels. Furthermore, we find that the cadherins Pcdh10, which is regulated by Pou3f1 and Hoxa5, and Cdh10, which is controlled by Pou3f1, are both mediators of like-like clustering of motor neuron cell bodies. This specific Pcdh10/Cdh10 activity might provide the means by which phrenic neurons are assembled into a distinct nucleus. Our study provides a framework for understanding how phrenic neuron identity is conferred and will help to generate this rare and inaccessible yet vital neuronal subtype directly from pluripotent stem cells, thus facilitating subsequent functional investigations. PMID:24496616

Reconstruction of phrenic neuron identity in embryonic stem cell-derived motor neurons.

PubMed

Machado, Carolina Barcellos; Kanning, Kevin C; Kreis, Patricia; Stevenson, Danielle; Crossley, Martin; Nowak, Magdalena; Iacovino, Michelina; Kyba, Michael; Chambers, David; Blanc, Eric; Lieberam, Ivo

2014-02-01

Air breathing is an essential motor function for vertebrates living on land. The rhythm that drives breathing is generated within the central nervous system and relayed via specialised subsets of spinal motor neurons to muscles that regulate lung volume. In mammals, a key respiratory muscle is the diaphragm, which is innervated by motor neurons in the phrenic nucleus. Remarkably, relatively little is known about how this crucial subtype of motor neuron is generated during embryogenesis. Here, we used direct differentiation of motor neurons from mouse embryonic stem cells as a tool to identify genes that direct phrenic neuron identity. We find that three determinants, Pou3f1, Hoxa5 and Notch, act in combination to promote a phrenic neuron molecular identity. We show that Notch signalling induces Pou3f1 in developing motor neurons in vitro and in vivo. This suggests that the phrenic neuron lineage is established through a local source of Notch ligand at mid-cervical levels. Furthermore, we find that the cadherins Pcdh10, which is regulated by Pou3f1 and Hoxa5, and Cdh10, which is controlled by Pou3f1, are both mediators of like-like clustering of motor neuron cell bodies. This specific Pcdh10/Cdh10 activity might provide the means by which phrenic neurons are assembled into a distinct nucleus. Our study provides a framework for understanding how phrenic neuron identity is conferred and will help to generate this rare and inaccessible yet vital neuronal subtype directly from pluripotent stem cells, thus facilitating subsequent functional investigations.

Bolzano's Approach to the Paradoxes of Infinity: Implications for Teaching

ERIC Educational Resources Information Center

Waldegg, Guillermina

2005-01-01

In this paper we analyze excerpts of "Paradoxes of the Infinite", the posthumous work of Bernard Bolzano (1781-1848), in order to show that Georg Cantor's (1845-1918) approach to the problem of defining actual mathematical infinity is not the most natural. In fact, Bolzano's approach to the paradoxes of infinity is more intuitive, while remaining…

Winning Is(n't) Everything: The Paradox of Excellence and the Challenge of Organizational Epideictic

ERIC Educational Resources Information Center

Stahley, Melissa Bigam; Boyd, Josh

2006-01-01

Encompassing both the controlled messages of values advocacy and less explicit rhetorical actions such as philanthropy, community programs, and volunteerism, organizational epideictic affirms common values. This essay argues that such common values are problematized by the presence of paradox even in seemingly innocuous epideictic subjects.…

The mean, the median, and the St. Petersburg paradox

PubMed Central

Hayden, Benjamin Y.; Platt, Michael L.

2013-01-01

The St. Petersburg Paradox is a famous economic and philosophical puzzle that has generated numerous conflicting explanations. To shed empirical light on this phenomenon, we examined subjects’ bids for one St. Petersburg gamble with a real monetary payment. We found that bids were typically lower than twice the smallest payoff, and thus much lower than is generally supposed. We also examined bids offered for several hypothetical variants of the St. Petersburg Paradox. We found that bids were weakly affected by truncating the gamble, were strongly affected by repeats of the gamble, and depended linearly on the initial “seed” value of the gamble. One explanation, which we call the median heuristic, strongly predicts these data. Subjects following this strategy evaluate a gamble as if they were taking the median rather than the mean of the payoff distribution. Finally, we argue that the distribution of outcomes embodied in the St. Petersburg paradox is so divergent from the Gaussian form that the statistical mean is a poor estimator of expected value, so that the expected value of the St. Petersburg gamble is undefined. These results suggest that this classic paradox has a straightforward explanation rooted in the use of a statistical heuristic. PMID:24179560

The happiness–income paradox revisited

PubMed Central

Easterlin, Richard A.; McVey, Laura Angelescu; Switek, Malgorzata; Sawangfa, Onnicha; Zweig, Jacqueline Smith

2010-01-01

The striking thing about the happiness–income paradox is that over the long-term —usually a period of 10 y or more—happiness does not increase as a country's income rises. Heretofore the evidence for this was limited to developed countries. This article presents evidence that the long term nil relationship between happiness and income holds also for a number of developing countries, the eastern European countries transitioning from socialism to capitalism, and an even wider sample of developed countries than previously studied. It also finds that in the short-term in all three groups of countries, happiness and income go together, i.e., happiness tends to fall in economic contractions and rise in expansions. Recent critiques of the paradox, claiming the time series relationship between happiness and income is positive, are the result either of a statistical artifact or a confusion of the short-term relationship with the long-term one. PMID:21149705

An experimental study of the Online Information Paradox: Does en-route information improve road network performance?

PubMed Central

2017-01-01

This study investigates the empirical presence of a theoretical transportation paradox, defined as the “Online Information Paradox” (OIP). The paradox suggests that, for certain road networks, the provision of online information deteriorate travel conditions for all users of that network relative to the situation where no online information is provided to users. The analytical presence of the paradox was derived for a specific network structure by using two equilibrium models, the first being the Expected User Equilibrium (EUE) solution (no information scenario) and the other being the User Equilibrium with Recourse (UER) solution (with information scenario). An incentivised computerised route choice game was designed using the concepts of experimental economics and administered in a controlled laboratory environment to investigate the physical presence of the paradox. Aggregate statistics of path flows and Total System Travel Costs (TSTC) were used to compare the experimental results with the theoretical findings. A total of 12 groups of 12 participants completed the experiment and the OIP and the occurrence of the OIP being significant was observed in 11 of the 12 cases. Though information increased travel costs for users on average, it reduced the volatility of travel costs experienced in the no information scenario indicating that information can achieve a more reliable system. Further replications of similar experiments and more importantly field based identification of the phenomena will force transport professionals to be aware of the emergence of the paradox. In addition, studies such as this emphasise the need for the adoption of adaptive traffic assignment techniques to appropriately model the acquisition of information on a road network. PMID:28902854

A joint analysis of the Drake equation and the Fermi paradox

NASA Astrophysics Data System (ADS)

Prantzos, Nikos

2013-07-01

I propose a unified framework for a joint analysis of the Drake equation and the Fermi paradox, which enables a simultaneous, quantitative study of both of them. The analysis is based on a simplified form of the Drake equation and on a fairly simple scheme for the colonization of the Milky Way. It appears that for sufficiently long-lived civilizations, colonization of the Galaxy is the only reasonable option to gain knowledge about other life forms. This argument allows one to define a region in the parameter space of the Drake equation, where the Fermi paradox definitely holds (`Strong Fermi paradox').

Rhythmogenic neuronal networks, emergent leaders, and k-cores.

PubMed

Schwab, David J; Bruinsma, Robijn F; Feldman, Jack L; Levine, Alex J

2010-11-01

Neuronal network behavior results from a combination of the dynamics of individual neurons and the connectivity of the network that links them together. We study a simplified model, based on the proposal of Feldman and Del Negro (FDN) [Nat. Rev. Neurosci. 7, 232 (2006)], of the preBötzinger Complex, a small neuronal network that participates in the control of the mammalian breathing rhythm through periodic firing bursts. The dynamics of this randomly connected network of identical excitatory neurons differ from those of a uniformly connected one. Specifically, network connectivity determines the identity of emergent leader neurons that trigger the firing bursts. When neuronal desensitization is controlled by the number of input signals to the neurons (as proposed by FDN), the network's collective desensitization--required for successful burst termination--is mediated by k-core clusters of neurons.

Adaptationism Fails to Resolve Fermi's Paradox

NASA Astrophysics Data System (ADS)

Cirkovic, M. M.; Dragicevic, I.; Beric-Bjedov, T.

2005-06-01

One of the most interesting problems in the nascent discipline of astrobiology is more than half-century old Fermi's paradox: why, considering extraordinary young age of Earth and the Solar System in the Galactic context, don't we perceive much older intelligent communities or signposts of their activity? In spite of a vigorous research activity in recent years, especially bolstered by successes of astrobiology in finding extrasolar planets and extremophiles, this problem (also known as the "Great Silence" or "astrosociological" paradox) remains as open as ever. In a previous paper, we have discussed a particular evolutionary solution suggested by Karl Schroeder based on the currently dominant evolutionary doctrine of adaptationism. Here, we extend that discussion with emphasis on the problems such a solution is bound to face, and conclude that it is ultimately quite unlikely.

A subset of neurons controls the permeability of the peritrophic matrix and midgut structure in Drosophila adults.

PubMed

Kenmoku, Hiroyuki; Ishikawa, Hiroki; Ote, Manabu; Kuraishi, Takayuki; Kurata, Shoichiro

2016-08-01

The metazoan gut performs multiple physiological functions, including digestion and absorption of nutrients, and also serves as a physical and chemical barrier against ingested pathogens and abrasive particles. Maintenance of these functions and structures is partly controlled by the nervous system, yet the precise roles and mechanisms of the neural control of gut integrity remain to be clarified in Drosophila Here, we screened for GAL4 enhancer-trap strains and labeled a specific subsets of neurons, using Kir2.1 to inhibit their activity. We identified an NP3253 line that is susceptible to oral infection by Gram-negative bacteria. The subset of neurons driven by the NP3253 line includes some of the enteric neurons innervating the anterior midgut, and these flies have a disorganized proventricular structure with high permeability of the peritrophic matrix and epithelial barrier. The findings of the present study indicate that neural control is crucial for maintaining the barrier function of the gut, and provide a route for genetic dissection of the complex brain-gut axis in adults of the model organism Drosophila. © 2016. Published by The Company of Biologists Ltd.

The neuronal control of cardiac functions in Molluscs☆

PubMed Central

Kodirov, Sodikdjon A.

2017-01-01

In this manuscript, I review the current and relevant classical studies on properties of the Mollusca heart and their central nervous system including ganglia, neurons, and nerves involved in cardiomodulation. Similar to mammalian brain hemispheres, these invertebrates possess symmetrical pairs of ganglia albeit visceral (only one) ganglion and the parietal ganglia (the right ganglion is bigger than the left one). Furthermore, there are two major regulatory drives into the compartments (pericard, auricle, and ventricle) and cardiomyocytes of the heart. These are the excitatory and inhibitory signals that originate from a few designated neurons and their putative neurotransmitters. Many of these neurons are well-identified, their specific locations within the corresponding ganglion are mapped, and some are termed as either heart excitatory (HE) or inhibitory (HI) cells. The remaining neurons are classified as cardio-regulatory, and their direct and indirect actions on the heart’s function have been documented. The cardiovascular anatomy of frequently used experimental animals, Achatina, Aplysia, Helix, and Lymnaea is relatively simple. However, as in humans, it possesses all major components including even trabeculae and atrio-ventricular valves. Since the myocardial cells are enzymatically dispersible, multiple voltage dependent cationic currents in isolated cardiomyocytes are described. The latter include at least the A-type K+, delayed rectifier K+, TTX-sensitive Na+, and L-type Ca2+ channels. PMID:21736949

Control of Amygdala Circuits by 5-HT Neurons via 5-HT and Glutamate Cotransmission.

PubMed

Sengupta, Ayesha; Bocchio, Marco; Bannerman, David M; Sharp, Trevor; Capogna, Marco

2017-02-15

The serotonin (5-HT) system and the amygdala are key regulators of emotional behavior. Several lines of evidence suggest that 5-HT transmission in the amygdala is implicated in the susceptibility and drug treatment of mood disorders. Therefore, elucidating the physiological mechanisms through which midbrain 5-HT neurons modulate amygdala circuits could be pivotal in understanding emotional regulation in health and disease. To shed light on these mechanisms, we performed patch-clamp recordings from basal amygdala (BA) neurons in brain slices from mice with channelrhodopsin genetically targeted to 5-HT neurons. Optical stimulation of 5-HT terminals at low frequencies (≤1 Hz) evoked a short-latency excitation of BA interneurons (INs) that was depressed at higher frequencies. Pharmacological analysis revealed that this effect was mediated by glutamate and not 5-HT because it was abolished by ionotropic glutamate receptor antagonists. Optical stimulation of 5-HT terminals at higher frequencies (10-20 Hz) evoked both slow excitation and slow inhibition of INs. These effects were mediated by 5-HT because they were blocked by antagonists of 5-HT 2A and 5-HT 1A receptors, respectively. These fast glutamate- and slow 5-HT-mediated responses often coexisted in the same neuron. Interestingly, fast-spiking and non-fast-spiking INs displayed differential modulation by glutamate and 5-HT. Furthermore, optical stimulation of 5-HT terminals did not evoke glutamate release onto BA principal neurons, but inhibited these cells directly via activation of 5-HT 1A receptors and indirectly via enhanced GABA release. Collectively, these findings suggest that 5-HT neurons exert a frequency-dependent, cell-type-specific control over BA circuitry via 5-HT and glutamate co-release to inhibit the BA output. SIGNIFICANCE STATEMENT The modulation of the amygdala by serotonin (5-HT) is important for emotional regulation and is implicated in the pathogenesis and treatment of affective disorders

Control of Amygdala Circuits by 5-HT Neurons via 5-HT and Glutamate Cotransmission

PubMed Central

Bannerman, David M.

2017-01-01

The serotonin (5-HT) system and the amygdala are key regulators of emotional behavior. Several lines of evidence suggest that 5-HT transmission in the amygdala is implicated in the susceptibility and drug treatment of mood disorders. Therefore, elucidating the physiological mechanisms through which midbrain 5-HT neurons modulate amygdala circuits could be pivotal in understanding emotional regulation in health and disease. To shed light on these mechanisms, we performed patch-clamp recordings from basal amygdala (BA) neurons in brain slices from mice with channelrhodopsin genetically targeted to 5-HT neurons. Optical stimulation of 5-HT terminals at low frequencies (≤1 Hz) evoked a short-latency excitation of BA interneurons (INs) that was depressed at higher frequencies. Pharmacological analysis revealed that this effect was mediated by glutamate and not 5-HT because it was abolished by ionotropic glutamate receptor antagonists. Optical stimulation of 5-HT terminals at higher frequencies (10–20 Hz) evoked both slow excitation and slow inhibition of INs. These effects were mediated by 5-HT because they were blocked by antagonists of 5-HT2A and 5-HT1A receptors, respectively. These fast glutamate- and slow 5-HT-mediated responses often coexisted in the same neuron. Interestingly, fast-spiking and non-fast-spiking INs displayed differential modulation by glutamate and 5-HT. Furthermore, optical stimulation of 5-HT terminals did not evoke glutamate release onto BA principal neurons, but inhibited these cells directly via activation of 5-HT1A receptors and indirectly via enhanced GABA release. Collectively, these findings suggest that 5-HT neurons exert a frequency-dependent, cell-type-specific control over BA circuitry via 5-HT and glutamate co-release to inhibit the BA output. SIGNIFICANCE STATEMENT The modulation of the amygdala by serotonin (5-HT) is important for emotional regulation and is implicated in the pathogenesis and treatment of affective disorders

Activity of Raphé Serotonergic Neurons Controls Emotional Behaviors.

PubMed

Teissier, Anne; Chemiakine, Alexei; Inbar, Benjamin; Bagchi, Sneha; Ray, Russell S; Palmiter, Richard D; Dymecki, Susan M; Moore, Holly; Ansorge, Mark S

2015-12-01

Despite the well-established role of serotonin signaling in mood regulation, causal relationships between serotonergic neuronal activity and behavior remain poorly understood. Using a pharmacogenetic approach, we find that selectively increasing serotonergic neuronal activity in wild-type mice is anxiogenic and reduces floating in the forced-swim test, whereas inhibition has no effect on the same measures. In a developmental mouse model of altered emotional behavior, increased anxiety and depression-like behaviors correlate with reduced dorsal raphé and increased median raphé serotonergic activity. These mice display blunted responses to serotonergic stimulation and behavioral rescues through serotonergic inhibition. Furthermore, we identify opposing consequences of dorsal versus median raphé serotonergic neuron inhibition on floating behavior, together suggesting that median raphé hyperactivity increases anxiety, whereas a low dorsal/median raphé serotonergic activity ratio increases depression-like behavior. Thus, we find a critical role of serotonergic neuronal activity in emotional regulation and uncover opposing roles of median and dorsal raphé function. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Revisiting the 'Low BirthWeight paradox' using a model-based definition.

PubMed

Juárez, Sol; Ploubidis, George B; Clarke, Lynda

2014-01-01

Immigrant mothers in Spain have a lower risk of delivering Low BirthWeight (LBW) babies in comparison to Spaniards (LBW paradox). This study aimed at revisiting this finding by applying a model-based threshold as an alternative to the conventional definition of LBW. Vital information data from Madrid was used (2005-2006). LBW was defined in two ways (less than 2500g and Wilcox's proposal). Logistic and linear regression models were run. According to common definition of LBW (less than 2500g) there is evidence to support the LBW paradox in Spain. Nevertheless, when an alternative model-based definition of LBW is used, the paradox is only clearly present in mothers from the rest of Southern America, suggesting a possible methodological bias effect. In the future, any examination of the existence of the LBW paradox should incorporate model-based definitions of LBW in order to avoid methodological bias. Copyright © 2013 SESPAS. Published by Elsevier Espana. All rights reserved.

Generalized friendship paradox in complex networks: The case of scientific collaboration

PubMed Central

Eom, Young-Ho; Jo, Hang-Hyun

2014-01-01

The friendship paradox states that your friends have on average more friends than you have. Does the paradox “hold” for other individual characteristics like income or happiness? To address this question, we generalize the friendship paradox for arbitrary node characteristics in complex networks. By analyzing two coauthorship networks of Physical Review journals and Google Scholar profiles, we find that the generalized friendship paradox (GFP) holds at the individual and network levels for various characteristics, including the number of coauthors, the number of citations, and the number of publications. The origin of the GFP is shown to be rooted in positive correlations between degree and characteristics. As a fruitful application of the GFP, we suggest effective and efficient sampling methods for identifying high characteristic nodes in large-scale networks. Our study on the GFP can shed lights on understanding the interplay between network structure and node characteristics in complex networks. PMID:24714092

Sleep-Active Neurons: Conserved Motors of Sleep

PubMed Central

Bringmann, Henrik

2018-01-01

Sleep is crucial for survival and well-being. This behavioral and physiological state has been studied in all major genetically accessible model animals, including rodents, fish, flies, and worms. Genetic and optogenetic studies have identified several neurons that control sleep, making it now possible to compare circuit mechanisms across species. The “motor” of sleep across animal species is formed by neurons that depolarize at the onset of sleep to actively induce this state by directly inhibiting wakefulness. These sleep-inducing neurons are themselves controlled by inhibitory or activating upstream pathways, which act as the “drivers” of the sleep motor: arousal inhibits “sleep-active” neurons whereas various sleep-promoting “tiredness” pathways converge onto sleep-active neurons to depolarize them. This review provides the first overview of sleep-active neurons across the major model animals. The occurrence of sleep-active neurons and their regulation by upstream pathways in both vertebrate and invertebrate species suggests that these neurons are general and ancient components that evolved early in the history of nervous systems. PMID:29618588

Integrated microfluidic platforms for investigating neuronal networks

NASA Astrophysics Data System (ADS)

Kim, Hyung Joon

This dissertation describes the development and application of integrated microfluidics-based assay platforms to study neuronal activities in the nervous system in-vitro. The assay platforms were fabricated using soft lithography and micro/nano fabrication including microfluidics, surface patterning, and nanomaterial synthesis. The use of integrated microfluidics-based assay platform allows culturing and manipulating many types of neuronal tissues in precisely controlled microenvironment. Furthermore, they provide organized multi-cellular in-vitro model, long-term monitoring with live cell imaging, and compatibility with molecular biology techniques and electrophysiology experiment. In this dissertation, the integrated microfluidics-based assay platforms are developed for investigation of neuronal activities such as local protein synthesis, impairment of axonal transport by chemical/physical variants, growth cone path finding under chemical/physical cues, and synaptic transmission in neuronal circuit. Chapter 1 describes the motivation, objectives, and scope for developing in-vitro platform to study various neuronal activities. Chapter 2 introduces microfluidic culture platform for biochemical assay with large-scale neuronal tissues that are utilized as model system in neuroscience research. Chapter 3 focuses on the investigation of impaired axonal transport by beta-Amyloid and oxidative stress. The platform allows to control neuronal processes and to quantify mitochondrial movement in various regions of axons away from applied drugs. Chapter 4 demonstrates the development of microfluidics-based growth cone turning assay to elucidate the mechanism underlying axon guidance under soluble factors and shear flow. Using this platform, the behaviors of growth cone of mammalian neurons are verified under the gradient of inhibitory molecules and also shear flow in well-controlled manner. In Chapter 5, I combine in-vitro multicellular model with microfabricated MEA

A Hebbian learning rule gives rise to mirror neurons and links them to control theoretic inverse models.

PubMed

Hanuschkin, A; Ganguli, S; Hahnloser, R H R

2013-01-01

Mirror neurons are neurons whose responses to the observation of a motor act resemble responses measured during production of that act. Computationally, mirror neurons have been viewed as evidence for the existence of internal inverse models. Such models, rooted within control theory, map-desired sensory targets onto the motor commands required to generate those targets. To jointly explore both the formation of mirrored responses and their functional contribution to inverse models, we develop a correlation-based theory of interactions between a sensory and a motor area. We show that a simple eligibility-weighted Hebbian learning rule, operating within a sensorimotor loop during motor explorations and stabilized by heterosynaptic competition, naturally gives rise to mirror neurons as well as control theoretic inverse models encoded in the synaptic weights from sensory to motor neurons. Crucially, we find that the correlational structure or stereotypy of the neural code underlying motor explorations determines the nature of the learned inverse model: random motor codes lead to causal inverses that map sensory activity patterns to their motor causes; such inverses are maximally useful, by allowing the imitation of arbitrary sensory target sequences. By contrast, stereotyped motor codes lead to less useful predictive inverses that map sensory activity to future motor actions. Our theory generalizes previous work on inverse models by showing that such models can be learned in a simple Hebbian framework without the need for error signals or backpropagation, and it makes new conceptual connections between the causal nature of inverse models, the statistical structure of motor variability, and the time-lag between sensory and motor responses of mirror neurons. Applied to bird song learning, our theory can account for puzzling aspects of the song system, including necessity of sensorimotor gating and selectivity of auditory responses to bird's own song (BOS) stimuli.

A Hebbian learning rule gives rise to mirror neurons and links them to control theoretic inverse models

PubMed Central

Hanuschkin, A.; Ganguli, S.; Hahnloser, R. H. R.

2013-01-01

Mirror neurons are neurons whose responses to the observation of a motor act resemble responses measured during production of that act. Computationally, mirror neurons have been viewed as evidence for the existence of internal inverse models. Such models, rooted within control theory, map-desired sensory targets onto the motor commands required to generate those targets. To jointly explore both the formation of mirrored responses and their functional contribution to inverse models, we develop a correlation-based theory of interactions between a sensory and a motor area. We show that a simple eligibility-weighted Hebbian learning rule, operating within a sensorimotor loop during motor explorations and stabilized by heterosynaptic competition, naturally gives rise to mirror neurons as well as control theoretic inverse models encoded in the synaptic weights from sensory to motor neurons. Crucially, we find that the correlational structure or stereotypy of the neural code underlying motor explorations determines the nature of the learned inverse model: random motor codes lead to causal inverses that map sensory activity patterns to their motor causes; such inverses are maximally useful, by allowing the imitation of arbitrary sensory target sequences. By contrast, stereotyped motor codes lead to less useful predictive inverses that map sensory activity to future motor actions. Our theory generalizes previous work on inverse models by showing that such models can be learned in a simple Hebbian framework without the need for error signals or backpropagation, and it makes new conceptual connections between the causal nature of inverse models, the statistical structure of motor variability, and the time-lag between sensory and motor responses of mirror neurons. Applied to bird song learning, our theory can account for puzzling aspects of the song system, including necessity of sensorimotor gating and selectivity of auditory responses to bird's own song (BOS) stimuli. PMID

Cholinergic Neurons in the Basal Forebrain Promote Wakefulness by Actions on Neighboring Non-Cholinergic Neurons: An Opto-Dialysis Study.

PubMed

Zant, Janneke C; Kim, Tae; Prokai, Laszlo; Szarka, Szabolcs; McNally, James; McKenna, James T; Shukla, Charu; Yang, Chun; Kalinchuk, Anna V; McCarley, Robert W; Brown, Ritchie E; Basheer, Radhika

2016-02-10

Understanding the control of sleep-wake states by the basal forebrain (BF) poses a challenge due to the intermingled presence of cholinergic, GABAergic, and glutamatergic neurons. All three BF neuronal subtypes project to the cortex and are implicated in cortical arousal and sleep-wake control. Thus, nonspecific stimulation or inhibition studies do not reveal the roles of these different neuronal types. Recent studies using optogenetics have shown that "selective" stimulation of BF cholinergic neurons increases transitions between NREM sleep and wakefulness, implicating cholinergic projections to cortex in wake promotion. However, the interpretation of these optogenetic experiments is complicated by interactions that may occur within the BF. For instance, a recent in vitro study from our group found that cholinergic neurons strongly excite neighboring GABAergic neurons, including the subset of cortically projecting neurons, which contain the calcium-binding protein, parvalbumin (PV) (Yang et al., 2014). Thus, the wake-promoting effect of "selective" optogenetic stimulation of BF cholinergic neurons could be mediated by local excitation of GABA/PV or other non-cholinergic BF neurons. In this study, using a newly designed opto-dialysis probe to couple selective optical stimulation with simultaneous in vivo microdialysis, we demonstrated that optical stimulation of cholinergic neurons locally increased acetylcholine levels and increased wakefulness in mice. Surprisingly, the enhanced wakefulness caused by cholinergic stimulation was abolished by simultaneous reverse microdialysis of cholinergic receptor antagonists into BF. Thus, our data suggest that the wake-promoting effect of cholinergic stimulation requires local release of acetylcholine in the basal forebrain and activation of cortically projecting, non-cholinergic neurons, including the GABAergic/PV neurons. Optogenetics is a revolutionary tool to assess the roles of particular groups of neurons in behavioral

Cholinergic Neurons in the Basal Forebrain Promote Wakefulness by Actions on Neighboring Non-Cholinergic Neurons: An Opto-Dialysis Study

PubMed Central

Zant, Janneke C.; Kim, Tae; Prokai, Laszlo; Szarka, Szabolcs; McNally, James; McKenna, James T.; Shukla, Charu; Yang, Chun; Kalinchuk, Anna V.; McCarley, Robert W.; Brown, Ritchie E.

2016-01-01

Understanding the control of sleep–wake states by the basal forebrain (BF) poses a challenge due to the intermingled presence of cholinergic, GABAergic, and glutamatergic neurons. All three BF neuronal subtypes project to the cortex and are implicated in cortical arousal and sleep–wake control. Thus, nonspecific stimulation or inhibition studies do not reveal the roles of these different neuronal types. Recent studies using optogenetics have shown that “selective” stimulation of BF cholinergic neurons increases transitions between NREM sleep and wakefulness, implicating cholinergic projections to cortex in wake promotion. However, the interpretation of these optogenetic experiments is complicated by interactions that may occur within the BF. For instance, a recent in vitro study from our group found that cholinergic neurons strongly excite neighboring GABAergic neurons, including the subset of cortically projecting neurons, which contain the calcium-binding protein, parvalbumin (PV) (Yang et al., 2014). Thus, the wake-promoting effect of “selective” optogenetic stimulation of BF cholinergic neurons could be mediated by local excitation of GABA/PV or other non-cholinergic BF neurons. In this study, using a newly designed opto-dialysis probe to couple selective optical stimulation with simultaneous in vivo microdialysis, we demonstrated that optical stimulation of cholinergic neurons locally increased acetylcholine levels and increased wakefulness in mice. Surprisingly, the enhanced wakefulness caused by cholinergic stimulation was abolished by simultaneous reverse microdialysis of cholinergic receptor antagonists into BF. Thus, our data suggest that the wake-promoting effect of cholinergic stimulation requires local release of acetylcholine in the basal forebrain and activation of cortically projecting, non-cholinergic neurons, including the GABAergic/PV neurons. SIGNIFICANCE STATEMENT Optogenetics is a revolutionary tool to assess the roles of

Management of Paradoxical Response in Pediatric Tubercular Meningitis with Methylprednisolone

PubMed Central

Nema, Nitin; Verma, Abha; Singh, Kuldeep; Mehar, Virendra

2014-01-01

Paradoxical response to anti-tubercular drugs remains a diagnostic dilemma. In India where tuberculosis is quite prevalent, paradoxical response to anti-tubercular treatment (ATT) is either misdiagnosed or under-diagnosed. We report two cases of optochiasmatic arachnoiditis due to paradoxical response in children suffering from tuberculous meningitis. Visual acuity was recorded as no light perception in all eyes of both patients while they were taking 4-drug ATT (isoniazid, rifampicin, pyrazinamide and ethambutol). However their systemic conditions did not worsen. They were treated with intravenous methylprednisolone for five days followed by systemic corticosteroids on a tapering dose for four weeks along with ATT. This case report highlights the importance of early recognition of this sight-threatening complication and timely, effective treatment to prevent permanent blindness. PMID:24791114

Does an Obesity Paradox Really Exist After Cardiovascular Intervention?: A Systematic Review and Meta-Analysis of Randomized Controlled Trials and Observational Studies.

PubMed

Bundhun, Pravesh Kumar; Li, Nuo; Chen, Meng-Hua

2015-11-01

Several studies have shown the existence of an obesity paradox after Percutaneous Coronary Intervention (PCI). However, other studies have shown its absence. This study sought to perform a systematic review and meta-analysis of studies comparing the mortality risk between high body mass index patients and normal weight patients after PCI.We have searched PubMed, Embase, and Chinese medical journal for randomized controlled trials (RCTs) and observational studies published between the year 2000 and 2015 by typing the keywords "percutaneous coronary intervention" and "obesity paradox." The main outcome was "all-cause mortality". RevMan 5.3 software was used to calculate the risk ratio (RR) with 95% confidence interval (CI) to express the pooled effect on discontinuous variables.Twenty-two studies have been included in this meta-analysis consisting of a total of 242,377 patients with 73,143 normal weight patients, 103,608 overweight, and 65,626 obese patients. Younger age, higher cardiovascular risk factors and the intensive use of medications have mainly been observed among obese patients followed by overweight and normal weight patients respectively. In-hospital, 12 months and ≥ 1 year (long-term) mortality risks were significantly lower in the overweight and obese groups with (RR: 0.67; 95% CI: 0.63-0.72, P < 0.00001) and (RR: 0.60; 95% CI: 0.56-0.65, P < 0.00001) respectively in the in-hospital follow-up (RR: 0.62; 95% CI: 0.55-0.71 and 0.57; 95% CI: 0.52-0.63, P < 0.00001) at 12 months, and (RR: 0.70; 95% CI: 0.64-0.76; P < 0.00001) and (RR: 0.80; 95% CI: 0.71-0.91, P = 0.0006) respectively for the long-term follow-up after PCI.This "obesity paradox" does exist after PCI. The mortality in overweight and obese patients is really significantly lower compared to the normal weight patients. However, the exact reasons for this phenomenon need further exploration and research in the future.

Ionic mechanisms of spinal neuronal cold hypersensitivity in ciguatera.

PubMed

Patel, Ryan; Brice, Nicola L; Lewis, Richard J; Dickenson, Anthony H

2015-12-01

Cold hypersensitivity is evident in a range of neuropathies and can evoke sensations of paradoxical burning cold pain. Ciguatoxin poisoning is known to induce a pain syndrome caused by consumption of contaminated tropical fish that can persist for months and include pruritus and cold allodynia; at present no suitable treatment is available. This study examined, for the first time, the neural substrates and molecular components of Pacific ciguatoxin-2-induced cold hypersensitivity. Electrophysiological recordings of dorsal horn lamina V/VI wide dynamic range neurones were made in non-sentient rats. Subcutaneous injection of 10 nm ciguatoxin-2 into the receptive field increased neuronal responses to innocuous and noxious cooling. In addition, neuronal responses to low-threshold but not noxious punctate mechanical stimuli were also elevated. The resultant cold hypersensitivity was not reversed by 6-({2-[2-fluoro-6-(trifluoromethyl)phenoxy]-2-methylpropyl}carbamoyl)pyridine-3-carboxylic acid, an antagonist of transient receptor potential melastatin 8 (TRPM8). Both mechanical and cold hypersensitivity were completely prevented by co-injection with the Nav 1.8 antagonist A803467, whereas the transient receptor potential ankyrin 1 (TRPA1) antagonist A967079 only prevented hypersensitivity to innocuous cooling and partially prevented hypersensitivity to noxious cooling. In naive rats, neither innocuous nor noxious cold-evoked neuronal responses were inhibited by antagonists of Nav 1.8, TRPA1 or TRPM8 alone. Ciguatoxins may confer cold sensitivity to a subpopulation of cold-insensitive Nav 1.8/TRPA1-positive primary afferents, which could underlie the cold allodynia reported in ciguatera. These data expand the understanding of central spinal cold sensitivity under normal conditions and the role of these ion channels in this translational rat model of ciguatoxin-induced hypersensitivity. © 2015 The Authors. European Journal of Neuroscience published by Federation of

Somatomotor and oculomotor inferior olivary neurons have distinct electrophysiological phenotypes

PubMed Central

Urbano, Francisco J.; Simpson, John I.; Llinás, Rodolfo R.

2006-01-01

The electrophysiological properties of rat inferior olive (IO) neurons in the dorsal cap of Kooy (DCK) and the adjacent ventrolateral outgrowth (VLO) were compared with those of IO neurons in the principal olive (PO). Whereas DCK/VLO neurons are involved in eye movement control via their climbing fiber projection to the cerebellar flocculus, PO neurons control limb and digit movements via their climbing fiber projection to the lateral cerebellar hemisphere. In vitro patch recordings from DCK/VLO neurons revealed that low threshold calcium currents, Ih currents, and subthreshold oscillations are lacking in this subset of IO neurons. The recordings of activity in DCK neurons obtained by using voltage-sensitive dye imaging showed that activity is not limited to a single neuron, but rather that clusters of DCK neurons can be active in unison. These electrophysiological results show that the DCK/VLO neurons have unique properties that set them apart from the neurons in the PO nucleus. This finding indicates that motor control, from the perspective of the olivocerebellar system, is fundamentally different for the oculomotor and the somatomotor systems. PMID:17050678

The effect of smoking on lung cancer: ethnic differences and the smoking paradox

PubMed Central

2016-01-01

The objectives of this review were to determine whether the smoking paradox still exists and to summarize possible explanations for the smoking paradox. Based on published data, we compared the risk of cigarette smoking for lung cancer in Western and Asian countries. We extracted data from the relevant studies about annual tobacco consumption, lung cancer mortality rates according to smoking status from each country, and possible explanations for the smoking paradox. A significantly greater risk of lung cancer death was found among current smokers in Asian countries than among nonsmokers, with relative risks (RRs) of 4.0 to 4.6 for Koreans, 3.7 to 5.1 for Japanese, and 2.4 to 6.5 for Chinese. Although a significantly greater risk of lung cancer was present among current smokers in Asian countries, the RRs in Asian countries were much lower than those reported in Western countries (range, 9.4 to 23.2). Possible explanations for the smoking paradox included epidemiologic characteristics, such as the smoking amount, age at smoking initiation, and the use of filtered or mild tobacco. The smoking paradox definitely exists, but may be explained by major epidemiologic characteristics. Therefore, the smoking paradox should not be interpreted as indicating that tobacco is safer or less harmful for Asians. PMID:28092929

MCM Paradox: Abundance of Eukaryotic Replicative Helicases and Genomic Integrity.

PubMed

Das, Mitali; Singh, Sunita; Pradhan, Satyajit; Narayan, Gopeshwar

2014-01-01

As a crucial component of DNA replication licensing system, minichromosome maintenance (MCM) 2-7 complex acts as the eukaryotic DNA replicative helicase. The six related MCM proteins form a heterohexamer and bind with ORC, CDC6, and Cdt1 to form the prereplication complex. Although the MCMs are well known as replicative helicases, their overabundance and distribution patterns on chromatin present a paradox called the "MCM paradox." Several approaches had been taken to solve the MCM paradox and describe the purpose of excess MCMs distributed beyond the replication origins. Alternative functions of these MCMs rather than a helicase had also been proposed. This review focuses on several models and concepts generated to solve the MCM paradox coinciding with their helicase function and provides insight into the concept that excess MCMs are meant for licensing dormant origins as a backup during replication stress. Finally, we extend our view towards the effect of alteration of MCM level. Though an excess MCM constituent is needed for normal cells to withstand stress, there must be a delineation of the threshold level in normal and malignant cells. This review also outlooks the future prospects to better understand the MCM biology.

ApoER2 Controls Not Only Neuronal Migration in the Intermediate Zone But Also Termination of Migration in the Developing Cerebral Cortex.

PubMed

Hirota, Yuki; Kubo, Ken-Ichiro; Fujino, Takahiro; Yamamoto, Tokuo T; Nakajima, Kazunori

2018-01-01

Neuronal migration contributes to the establishment of mammalian brain. The extracellular protein Reelin sends signals to various downstream molecules by binding to its receptors, the apolipoprotein E receptor 2 (ApoER2) and very low-density lipoprotein receptor and exerts essential roles in the neuronal migration and formation of the layered neocortex. However, the cellular and molecular functions of Reelin signaling in the cortical development are not yet fully understood. Here, to gain insight into the role of Reelin signaling during cortical development, we examined the migratory behavior of Apoer2-deficient neurons in the developing brain. Stage-specific labeling of newborn neurons revealed that the neurons ectopically invaded the marginal zone (MZ) and that neuronal migration of both early- and late-born neurons was disrupted in the intermediate zone (IZ) in the Apoer2 KO mice. Rescue experiments showed that ApoER2 functions both in cell-autonomous and noncell-autonomous manners, that Rap1, integrin, and Akt are involved in the termination of migration beneath the MZ, and that Akt also controls neuronal migration in the IZ downstream of ApoER2. These data indicate that ApoER2 controls multiple processes in neuronal migration, including the early stage of radial migration and termination of migration beneath the MZ in the developing neocortex. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Molecular Pathological Epidemiology Gives Clues to Paradoxical Findings

PubMed Central

Nishihara, Reiko; VanderWeele, Tyler J.; Shibuya, Kenji; Mittleman, Murray A.; Wang, Molin; Field, Alison E.; Giovannucci, Edward; Lochhead, Paul; Ogino, Shuji

2015-01-01

A number of epidemiologic studies have described what appear to be paradoxical associations, where an incongruous relationship is observed between a certain well-established risk factor for disease incidence and favorable clinical outcome among patients with that disease. For example, the “obesity paradox” represents the association between obesity and better survival among patients with a certain disease such as coronary heart disease. Paradoxical observations cause vexing clinical and public health problems as they raise questions on causal relationships and hinder the development of effective interventions. Compelling evidence indicates that pathogenic processes encompass molecular alterations within cells and the microenvironment, influenced by various exogenous and endogenous exposures, and that interpersonal heterogeneity in molecular pathology and pathophysiology exists among patients with any given disease. In this article, we introduce methods of the emerging integrative interdisciplinary field of molecular pathological epidemiology (MPE), which is founded on the unique disease principle and disease continuum theory. We analyze and decipher apparent paradoxical findings, utilizing the MPE approach and available literature data on tumor somatic genetic and epigenetic characteristics. Through our analyses in colorectal cancer, renal cell carcinoma, and glioblastoma (malignant brain tumor), we can readily explain paradoxical associations between disease risk factors and better prognosis among disease patients. The MPE paradigm and approach can be applied to not only neoplasms but also various non-neoplastic diseases where there exists indisputable ubiquitous heterogeneity of pathogenesis and molecular pathology. The MPE paradigm including consideration of disease heterogeneity plays an essential role in advancements of precision medicine and public health. PMID:26445996

Granularity of the mirror neuron system: A complex endeavor. Comment on "Grasping synergies: A motor-control approach to the mirror neuron mechanism" by A. D'Ausilio et al.

NASA Astrophysics Data System (ADS)

Swinnen, S. P.; Alaerts, K.

2015-03-01

The review paper by D'Ausilio and coauthors [3] is very timely and addresses one of the long-standing issues with respect to the coding features of mirror neurons. Through the history of mirror neuron research, there has been some controversy with respect to the level of granularity of the mirror neuron system, as studied in animal and human systems. While some researchers have suggested that abstract (high level) features of movement are coded, others have claimed evidence for more muscle specific (low level) coding properties (for an example, see [1,2]). D'Ausilio et al. [3] take a strong position in their review, suggesting a convergence between basic mechanisms of movement control and the mirror neuron system. Their suggestion is inspired by Bernstein's influential work on the so-called degrees of freedom problem. Even though a goal can in principle be reached in an infinite number of ways, consistent and stereotypical patterns of kinematics and muscle activation are often observed [4]. This has led to the notion of movement synergies as the basic building blocks for movement control. Even though it is essentially possible to contract isolated muscles or even motor units, Bernstein suggested that control of complex movement relies on movement synergies or coordinative structures, referring to a group of muscles that behave as a functional unit. This reduces the computational demands of the central nervous system considerably by assigning more responsibility to the lower levels of the movement control system. Bernstein's approach has inspired the dynamical systems perspective that has focused on a better understanding of complex biological systems such as interlimb coordination in humans [8]. For example, the upper limbs behave as a coordinative structure whereby simultaneous activation of the homologous muscle groups constitutes the default or preferred coordination mode that has to be defied when alternative patterns of coordination need to be performed or

Qualities and Inequalities in Online Social Networks through the Lens of the Generalized Friendship Paradox.

PubMed

Momeni, Naghmeh; Rabbat, Michael

2016-01-01

The friendship paradox is the phenomenon that in social networks, people on average have fewer friends than their friends do. The generalized friendship paradox is an extension to attributes other than the number of friends. The friendship paradox and its generalized version have gathered recent attention due to the information they provide about network structure and local inequalities. In this paper, we propose several measures of nodal qualities which capture different aspects of their activities and influence in online social networks. Using these measures we analyse the prevalence of the generalized friendship paradox over Twitter and we report high levels of prevalence (up to over 90% of nodes). We contend that this prevalence of the friendship paradox and its generalized version arise because of the hierarchical nature of the connections in the network. This hierarchy is nested as opposed to being star-like. We conclude that these paradoxes are collective phenomena not created merely by a minority of well-connected or high-attribute nodes. Moreover, our results show that a large fraction of individuals can experience the generalized friendship paradox even in the absence of a significant correlation between degrees and attributes.

Parkin Mutations Reduce the Complexity of Neuronal Processes in iPSC-derived Human Neurons

PubMed Central

Ren, Yong; Jiang, Houbo; Hu, Zhixing; Fan, Kevin; Wang, Jun; Janoschka, Stephen; Wang, Xiaomin; Ge, Shaoyu; Feng, Jian

2015-01-01

Parkinson’s disease (PD) is characterized by the degeneration of nigral dopaminergic (DA) neurons and non-DA neurons in many parts of the brain. Mutations of parkin, an E3 ubiquitin ligase that strongly binds to microtubules, are the most frequent cause of recessively inherited Parkinson’s disease. The lack of robust PD phenotype in parkin knockout mice suggests a unique vulnerability of human neurons to parkin mutations. Here, we show that the complexity of neuronal processes as measured by total neurite length, number of terminals, number of branch points and Sholl analysis, was greatly reduced in induced pluripotent stem cell (iPSC)-derived TH+ or TH− neurons from PD patients with parkin mutations. Consistent with these, microtubule stability was significantly decreased by parkin mutations in iPSC-derived neurons. Overexpression of parkin, but not its PD-linked mutant nor GFP, restored the complexity of neuronal processes and the stability of microtubules. Consistent with these, the microtubule-depolymerizing agent colchicine mimicked the effect of parkin mutations by decreasing neurite length and complexity in control neurons while the microtubule-stabilizing drug taxol mimicked the effect of parkin overexpression by enhancing the morphology of parkin-deficient neurons. The results suggest that parkin maintains the morphological complexity of human neurons by stabilizing microtubules. PMID:25332110

Crosstalks between kisspeptin neurons and somatostatin neurons are not photoperiod dependent in the ewe hypothalamus.

PubMed

Dufourny, Laurence; Lomet, Didier

2017-12-01

Seasonal reproduction is under the control of gonadal steroid feedback, itself synchronized by day-length or photoperiod. As steroid action on GnRH neurons is mostly indirect and therefore exerted through interneurons, we looked for neuroanatomical interactions between kisspeptin (KP) neurons and somatostatin (SOM) neurons, two populations targeted by sex steroids, in three diencephalic areas involved in the central control of ovulation and/or sexual behavior: the arcuate nucleus (ARC), the preoptic area (POA) and the ventrolateral part of the ventromedial hypothalamus (VMHvl). KP is the most potent secretagogue of GnRH secretion while SOM has been shown to centrally inhibit LH pulsatile release. Notably, hypothalamic contents of these two neuropeptides vary with photoperiod in specific seasonal species. Our hypothesis is that SOM inhibits KP neuron activity and therefore indirectly modulate GnRH release and that this effect may be seasonally regulated. We used sections from ovariectomized estradiol-replaced ewes killed after photoperiodic treatment mimicking breeding or anestrus season. We performed triple immunofluorescent labeling to simultaneously detect KP, SOM and synapsin, a marker for synaptic vesicles. Sections from the POA and from the mediobasal hypothalamus were examined using a confocal microscope. Randomly selected KP or SOM neurons were observed in the POA and ARC. SOM neurons were also observed in the VMHvl. In both the ARC and POA, nearly all KP neurons presented numerous SOM contacts. SOM neurons presented KP terminals more frequently in the ARC than in the POA and VMHvl. Quantitative analysis failed to demonstrate major seasonal variations of KP and SOM interactions. Our data suggest a possible inhibitory action of SOM on all KP neurons in both photoperiodic statuses. On the other hand, the physiological significance of KP modulation of SOM neuron activity and vice versa remain to be determined. Copyright © 2017 Elsevier Inc. All rights reserved.

Epidemiology of Myocardial Infarction Caused by Presumed Paradoxical Embolism via a Patent Foramen Ovale.

PubMed

Kleber, Franz X; Hauschild, Telse; Schulz, Antonia; Winkelmann, Anne; Bruch, Leonhard

2017-09-25

Despite several negative prospective randomized trials on the efficacy of patent foramen ovale (PFO) occlusion, the discussion on indications is ongoing. Because the incidence of paradoxical coronary embolism through a PFO is unknown, we investigated the risk of paradoxical embolic myocardial infarction over a period of 13 years.Methods and Results:We conducted a retrospective and a prospective study. In the former, we searched the hospital database of a tertiary referral center for cases of acute myocardial infarction (AMI) during the past 10 years and screened them for possible paradoxical MIs. On this basis we started a prospective evaluation over 39 months in another tertiary referral center. All patients with AMI and normal coronary arteries were screened for PFO and if no other reason for the AMI could be found, the case was judged as presumed paradoxical embolism. In the retrospective analysis we found 22 cases (0.45%) of presumed paradoxical coronary artery embolism under 4,848 AMI. In the prospective study there were 11 presumed paradoxical coronary artery embolisms among 1,654 patients with AMI, representing an incidence of 0.67%. Our findings demonstrated that well below 1% of AMIs are caused by paradoxical embolism via an interatrial communication. Although this percentage appears low, it is not a negligible number of patients based on the huge number of MIs occurring in the industrialized world.

Fibroblast growth factor receptor signaling affects development and function of dopamine neurons - inhibition results in a schizophrenia-like syndrome in transgenic mice.

PubMed

Klejbor, Ilona; Myers, Jason M; Hausknecht, Kathy; Corso, Thomas D; Gambino, Angelo S; Morys, Janusz; Maher, Pamela A; Hard, Robert; Richards, Jerry; Stachowiak, Ewa K; Stachowiak, Michal K

2006-06-01

Developing and mature midbrain dopamine (DA) neurons express fibroblast growth factor (FGF) receptor-1 (FGFR1). To determine the role of FGFR1 signaling in the development of DA neurons, we generated transgenic mice expressing a dominant negative mutant [FGFR1(TK-)] from the catecholaminergic, neuron-specific tyrosine hydroxylase (TH) gene promoter. In homozygous th(tk-)/th(tk-) mice, significant reductions in the size of TH-immunoreactive neurons were found in the substantia nigra compacta (SNc) and the ventral tegmental area (VTA) at postnatal days 0 and 360. Newborn th(tk-)/th(tk-) mice had a reduced density of DA neurons in both SNc and VTA, and the changes in SNc were maintained into adulthood. The reduced density of DA transporter in the striatum further demonstrated an impaired development of the nigro-striatal DA system. Paradoxically, the th(tk-)/th(tk-) mice had increased levels of DA, homovanilic acid and 3-methoxytyramine in the striatum, indicative of excessive DA transmission. These structural and biochemical changes in DA neurons are similar to those reported in human patients with schizophrenia and, furthermore, these th(tk-)/th(tk-) mice displayed an impaired prepulse inhibition that was reversed by a DA receptor antagonist. Thus, this study establishes a new developmental model for a schizophrenia-like disorder in which the inhibition of FGF signaling leads to alterations in DA neurons and DA-mediated behavior.

Neurons of self-defence: neuronal innervation of the exocrine defence glands in stick insects.

PubMed

Stolz, Konrad; von Bredow, Christoph-Rüdiger; von Bredow, Yvette M; Lakes-Harlan, Reinhard; Trenczek, Tina E; Strauß, Johannes

2015-01-01

Stick insects (Phasmatodea) use repellent chemical substances (allomones) for defence which are released from so-called defence glands in the prothorax. These glands differ in size between species, and are under neuronal control from the CNS. The detailed neural innervation and possible differences between species are not studied so far. Using axonal tracing, the neuronal innervation is investigated comparing four species. The aim is to document the complexity of defence gland innervation in peripheral nerves and central motoneurons in stick insects. In the species studied here, the defence gland is innervated by the intersegmental nerve complex (ISN) which is formed by three nerves from the prothoracic (T1) and suboesophageal ganglion (SOG), as well as a distinct suboesophageal nerve (Nervus anterior of the suboesophageal ganglion). In Carausius morosus and Sipyloidea sipylus, axonal tracing confirmed an innervation of the defence glands by this N. anterior SOG as well as N. anterior T1 and N. posterior SOG from the intersegmental nerve complex. In Peruphasma schultei, which has rather large defence glands, only the innervation by the N. anterior SOG was documented by axonal tracing. In the central nervous system of all species, 3-4 neuron types are identified by axonal tracing which send axons in the N. anterior SOG likely innervating the defence gland as well as adjacent muscles. These neurons are mainly suboesophageal neurons with one intersegmental neuron located in the prothoracic ganglion. The neuron types are conserved in the species studied, but the combination of neuron types is not identical. In addition, the central nervous system in S. sipylus contains one suboesophageal and one prothoracic neuron type with axons in the intersegmental nerve complex contacting the defence gland. Axonal tracing shows a very complex innervation pattern of the defence glands of Phasmatodea which contains different neurons in different nerves from two adjacent body segments

The Power of Why: Engaging the Goal Paradox in Program Evaluation

ERIC Educational Resources Information Center

Friedman, Victor J.; Rothman, Jay; Withers, Bill

2006-01-01

Clearly defined and measurable goals are commonly considered prerequisites for effective evaluation. Goal setting, however, presents a paradox to evaluators because it takes place at the interface of rationality and values. The objective of this article is to demonstrate a method for unlocking this paradox by making goal setting a process of…

Differential control of metabolic and cardiovascular functions by melanocortin-4 receptors in proopiomelanocortin neurons

PubMed Central

da Silva, Alexandre A.; Rushing, John S.; Pace, Benjamin; Hall, John E.

2013-01-01

We examined the role of melanocortin-4 receptors (MC4R) in proopiomelanocortin (Pomc) neurons in regulating metabolic and cardiovascular functions. Using Cre-loxP technology, we selectively rescued MC4R in Pomc neurons of mice with whole body MC4R deficiency (MC4R-Pomc-Cre mice). Body weight, food intake, and whole body oxygen consumption (V̇o2) were determined daily, and blood pressure (BP), heart rate (HR), and body temperature were measured 24 h/day by telemetry. An intracerebroventricular cannula was placed in the right lateral ventricle for intracerebroventricular infusions. Littermate MC4R-deficient (LoxTB-MC4R) mice were used as controls. After control measurements, the MC4R antagonist (SHU-9119; 1 nmol/h) was infused intracerebroventricularly for 7 days. Compared with LoxTB-MC4R mice, MC4R-Pomc-Cre mice were less obese (47 ± 2 vs. 52 ± 2 g) and had increased energy expenditure (2,174 ± 98 vs. 1,990 ± 68 ml·kg−1·min−1), but food intake (4.4 ± 0.2 vs. 4.3 ± 0.3 g/day), BP (112 ± 1 vs. 109 ± 3 mmHg), and HR [557 ± 9 vs. 551 ± 14 beats per minute (bpm)] were similar between groups. Chronic SHU-9119 infusion increased food intake (4.2 ± 0.2 to 6.1 ± 0.5 g/day) and body weight (47 ± 2 to 52 ± 2 g) in MC4R-Pomc-Cre mice, while no changes were observed in LoxTB-MC4R mice. Chronic SHU-9119 infusion also increased BP and HR by 5 ± 1 mmHg and 60 ± 8 bpm in MC4R-Pomc-Cre mice without altering BP or HR in LoxTB-MC4R mice. These results indicate that MC4Rs in Pomc neurons are important for regulation of energy balance. In contrast, while activation of MC4R in Pomc neurons facilitates the BP response to acute stress, our data do not support a major role of MC4R in Pomc neurons in regulating baseline BP and HR. PMID:23842677

Differential control of metabolic and cardiovascular functions by melanocortin-4 receptors in proopiomelanocortin neurons.

PubMed

do Carmo, Jussara M; da Silva, Alexandre A; Rushing, John S; Pace, Benjamin; Hall, John E

2013-08-15

We examined the role of melanocortin-4 receptors (MC4R) in proopiomelanocortin (Pomc) neurons in regulating metabolic and cardiovascular functions. Using Cre-loxP technology, we selectively rescued MC4R in Pomc neurons of mice with whole body MC4R deficiency (MC4R-Pomc-Cre mice). Body weight, food intake, and whole body oxygen consumption (Vo2) were determined daily, and blood pressure (BP), heart rate (HR), and body temperature were measured 24 h/day by telemetry. An intracerebroventricular cannula was placed in the right lateral ventricle for intracerebroventricular infusions. Littermate MC4R-deficient (LoxTB-MC4R) mice were used as controls. After control measurements, the MC4R antagonist (SHU-9119; 1 nmol/h) was infused intracerebroventricularly for 7 days. Compared with LoxTB-MC4R mice, MC4R-Pomc-Cre mice were less obese (47 ± 2 vs. 52 ± 2 g) and had increased energy expenditure (2,174 ± 98 vs. 1,990 ± 68 ml·kg⁻¹·min⁻¹), but food intake (4.4 ± 0.2 vs. 4.3 ± 0.3 g/day), BP (112 ± 1 vs. 109 ± 3 mmHg), and HR [557 ± 9 vs. 551 ± 14 beats per minute (bpm)] were similar between groups. Chronic SHU-9119 infusion increased food intake (4.2 ± 0.2 to 6.1 ± 0.5 g/day) and body weight (47 ± 2 to 52 ± 2 g) in MC4R-Pomc-Cre mice, while no changes were observed in LoxTB-MC4R mice. Chronic SHU-9119 infusion also increased BP and HR by 5 ± 1 mmHg and 60 ± 8 bpm in MC4R-Pomc-Cre mice without altering BP or HR in LoxTB-MC4R mice. These results indicate that MC4Rs in Pomc neurons are important for regulation of energy balance. In contrast, while activation of MC4R in Pomc neurons facilitates the BP response to acute stress, our data do not support a major role of MC4R in Pomc neurons in regulating baseline BP and HR.

Fatty acids increase neuronal hypertrophy of Pten knockdown neurons

PubMed Central

Fricano, Catherine J.; DeSpenza, Tyrone; Frazel, Paul W.; Li, Meijie; O'Malley, A. James; Westbrook, Gary L.; Luikart, Bryan W.

2014-01-01

Phosphatase and tensin homolog (Pten) catalyzes the reverse reaction of PI3K by dephosphorylating PIP3 to PIP2. This negatively regulates downstream Akt/mTOR/S6 signaling resulting in decreased cellular growth and proliferation. Co-injection of a lentivirus knocking Pten down with a control lentivirus allows us to compare the effects of Pten knockdown between individual neurons within the same animal. We find that knockdown of Pten results in neuronal hypertrophy by 21 days post-injection. This neuronal hypertrophy is correlated with increased p-S6 and p-mTOR in individual neurons. We used this system to test whether an environmental factor that has been implicated in cellular hypertrophy could influence the severity of the Pten knockdown-induced hypertrophy. Implantation of mini-osmotic pumps delivering fatty acids results in increased neuronal hypertrophy and p-S6/p-mTOR staining. These hypertrophic effects were reversed in response to rapamycin treatment. However, we did not observe a similar increase in hypertrophy in response to dietary manipulations of fatty acids. Thus, we conclude that by driving growth signaling with fatty acids and knocking down a critical regulator of growth, Pten, we are able to observe an additive morphological phenotype of increased soma size mediated by the mTOR pathway. PMID:24795563

Colloquium: The Einstein-Podolsky-Rosen paradox: From concepts to applications

NASA Astrophysics Data System (ADS)

Reid, M. D.; Drummond, P. D.; Bowen, W. P.; Cavalcanti, E. G.; Lam, P. K.; Bachor, H. A.; Andersen, U. L.; Leuchs, G.

2009-10-01

This Colloquium examines the field of the Einstein, Podolsky, and Rosen (EPR) gedanken experiment, from the original paper of Einstein, Podolsky, and Rosen, through to modern theoretical proposals of how to realize both the continuous-variable and discrete versions of the EPR paradox. The relationship with entanglement and Bell’s theorem are analyzed, and the progress to date towards experimental confirmation of the EPR paradox is summarized, with a detailed treatment of the continuous-variable paradox in laser-based experiments. Practical techniques covered include continuous-wave parametric amplifier and optical fiber quantum soliton experiments. Current proposals for extending EPR experiments to massive-particle systems are discussed, including spin squeezing, atomic position entanglement, and quadrature entanglement in ultracold atoms. Finally, applications of this technology to quantum key distribution, quantum teleportation, and entanglement swapping are examined.

Geologic appraisal of Paradox basin salt deposits for water emplacement

USGS Publications Warehouse

Hite, Robert J.; Lohman, Stanley William

1973-01-01

Thick salt deposits of Middle Pennsylvanian age are present in an area of 12,000 square miles in the Paradox basin of southeast Utah and southwest Colorado. The deposits are in the Paradox Member of the Hermosa Formation. The greatest thickness of this evaporite sequence is in a troughlike depression adjacent to the Uncompahgre uplift on the northeast side of the basin.The salt deposits consist of a cyclical sequence of thick halite units separated by thin units of black shale, dolomite, and anhydrite. Many halite units are several hundred feet thick and locally contain economically valuable potash deposits.Over much of the Paradox basin the salt deposits occur at depths of more than 5,000 feet. Only in a series of salt anticlines located along the northeastern side of the basin do the salt deposits rise to relatively shallow depths. The salt anticlines can be divided geographically and structurally into five major systems. Each system consists of a long undulating welt of thickened salt over which younger rocks are arched in anticlinal form. Locally there are areas along the axes of the anticlines where the Paradox Member was never covered by younger sediments. This allowed large-scale migration of Paradox strata toward and up through these holes in the sediment cover forming diapiric anticlines.The central or salt-bearing cores of the anticlines range in thickness from about 2,500 to 14,000 feet. Structure in the central core of the salt anticlines is the result of both regional-compression and flowage of the Paradox Member into the anticlines from adjacent synclines. Structure in the central cores of the salt anticlines ranges from relatively undeformed beds to complexly folded and faulted masses, in which stratigraphic continuity is undemonstrable.The presence of thick cap rock .over many of the salt anticlines is evidence of removal of large volumes of halite by groundwater. Available geologic and hydrologic information suggests that this is a relatively slow

Dynamics of neurons controlling movements of a locust hind leg. III. Extensor tibiae motor neurons.

PubMed

Newland, P L; Kondoh, Y

1997-06-01

Imposed movements of the apodeme of the femoral chordotonal organ (FeCO) of the locust hind leg elicit resistance reflexes in extensor and flexor tibiae motor neurons. The synaptic responses of the fast and slow extensor tibiae motor neurons (FETi and SETi, respectively) and the spike responses of SETi were analyzed with the use of the Wiener kernel white noise method to determine their response properties. The first-order Wiener kernels computed from soma recordings were essentially monophasic, or low passed, indicating that the motor neurons were primarily sensitive to the position of the tibia about the femorotibial joint. The responses of both extensor motor neurons had large nonlinear components. The second-order kernels of the synaptic responses of FETi and SETi had large on-diagonal peaks with two small off-diagonal valleys. That of SETi had an additional elongated valley on the diagonal, which was accompanied by two off-diagonal depolarizing peaks at a cutoff frequency of 58 Hz. These second-order components represent a half-wave rectification of the position-sensitive depolarizing response in FETi and SETi, and a delayed inhibitory input to SETi, indicating that both motor neurons were directionally sensitive. Model predictions of the responses of the motor neurons showed that the first-order (linear) characterization poorly predicted the actual responses of FETi and SETi to FeCO stimulation, whereas the addition of the second-order (nonlinear) term markedly improved the performance of the model. Simultaneous recordings from the soma and a neuropilar process of FETi showed that its synaptic responses to FeCO stimulation were phase delayed by about -30 degrees at 20 Hz, and reduced in amplitude by 30-40% when recorded in the soma. Similar configurations of the first and second-order kernels indicated that the primary process of FETi acted as a low-pass filter. Cross-correlation between a white noise stimulus and a unitized spike discharge of SETi again

Control of somatic membrane potential in nociceptive neurons and its implications for peripheral nociceptive transmission

PubMed Central

Du, Xiaona; Hao, Han; Gigout, Sylvain; Huang, Dongyang; Yang, Yuehui; Li, Li; Wang, Caixue; Sundt, Danielle; Jaffe, David B.; Zhang, Hailin; Gamper, Nikita

2014-01-01

Peripheral sensory ganglia contain somata of afferent fibres conveying somatosensory inputs to the central nervous system. Growing evidence suggests that the somatic/perisomatic region of sensory neurons can influence peripheral sensory transmission. Control of resting membrane potential (Erest) is an important mechanism regulating excitability, but surprisingly little is known about how Erest is regulated in sensory neuron somata or how changes in somatic/perisomatic Erest affect peripheral sensory transmission. We first evaluated the influence of several major ion channels on Erest in cultured small-diameter, mostly capsaicin-sensitive (presumed nociceptive) dorsal root ganglion (DRG) neurons. The strongest and most prevalent effect on Erest was achieved by modulating M channels, K2P and 4-aminopiridine-sensitive KV channels, while hyperpolarization-activated cyclic nucleotide-gated, voltage-gated Na+, and T-type Ca2+ channels to a lesser extent also contributed to Erest. Second, we investigated how varying somatic/perisomatic membrane potential, by manipulating ion channels of sensory neurons within the DRG, affected peripheral nociceptive transmission in vivo. Acute focal application of M or KATP channel enhancers or a hyperpolarization-activated cyclic nucleotide-gated channel blocker to L5 DRG in vivo significantly alleviated pain induced by hind paw injection of bradykinin. Finally, we show with computational modelling how somatic/perisomatic hyperpolarization, in concert with the low-pass filtering properties of the t-junction within the DRG, can interfere with action potential propagation. Our study deciphers a complement of ion channels that sets the somatic Erest of nociceptive neurons and provides strong evidence for a robust filtering role of the somatic and perisomatic compartments of peripheral nociceptive neuron. PMID:25168672

Neuronal codes for the inhibitory control of impulsive actions in the rat infralimbic cortex.

PubMed

Tsutsui-Kimura, Iku; Ohmura, Yu; Izumi, Takeshi; Matsushima, Toshiya; Amita, Hidetoshi; Yamaguchi, Taku; Yoshida, Takayuki; Yoshioka, Mitsuhiro

2016-01-01

Poor impulse control is a debilitating condition observed in various psychiatric disorders and could be a risk factor for drug addiction, criminal involvement, and suicide. The rat infralimbic cortex (IL), located in the ventral portion of the medial prefrontal cortex, has been implicated in impulse control. To elucidate the neurophysiological basis of impulse control, we recorded single unit activity in the IL of a rat performing a 3-choiceserial reaction time task (3-CSRTT) and 2-choice task (2-CT), which are animal models for impulsivity. The inactivation of IL neuronal activity with an injection of muscimol (0.1 μg /side) disrupted impulse control in the 3-CSRTT. More than 60% (38/56) of isolated IL units were linked to impulse control, while approximately 30% of all units were linked to attentional function in the 3-CSRTT. To avoid confounding motor-related units with the impulse control-related units, we further conducted the 2-CT in which the animals' motor activities were restricted during recording window. More than 30% (14/44) of recorded IL units were linked to impulse control in the 2-CT. Several types of impulse control-related units were identified. Only 16% of all units were compatible with the results of the muscimol experiment, which showed a transient decline in the firing rate immediately before the release of behavioral inhibition. This is the first study to elucidate the neurophysiological basis of impulse control in the IL and to propose that IL neurons control impulsive actions in a more complex manner than previously considered. Copyright © 2015 Elsevier B.V. All rights reserved.

Using affordable LED arrays for photo-stimulation of neurons.

PubMed

Valley, Matthew; Wagner, Sebastian; Gallarda, Benjamin W; Lledo, Pierre-Marie

2011-11-15

Standard slice electrophysiology has allowed researchers to probe individual components of neural circuitry by recording electrical responses of single cells in response to electrical or pharmacological manipulations(1,2). With the invention of methods to optically control genetically targeted neurons (optogenetics), researchers now have an unprecedented level of control over specific groups of neurons in the standard slice preparation. In particular, photosensitive channel rhodopsin-2 (ChR2) allows researchers to activate neurons with light(3,4). By combining careful calibration of LED-based photostimulation of ChR2 with standard slice electrophysiology, we are able to probe with greater detail the role of adult-born interneurons in the olfactory bulb, the first central relay of the olfactory system. Using viral expression of ChR2-YFP specifically in adult-born neurons, we can selectively control young adult-born neurons in a milieu of older and mature neurons. Our optical control uses a simple and inexpensive LED system, and we show how this system can be calibrated to understand how much light is needed to evoke spiking activity in single neurons. Hence, brief flashes of blue light can remotely control the firing pattern of ChR2-transduced newborn cells.

Mechanisms regulating neuronal excitability and seizure development following mTOR pathway hyperactivation.

PubMed

Lasarge, Candi L; Danzer, Steve C

2014-01-01

The phosphatidylinositol-3-kinase/phosphatase and tensin homolog (PTEN)-mammalian target of rapamycin (mTOR) pathway regulates a variety of neuronal functions, including cell proliferation, survival, growth, and plasticity. Dysregulation of the pathway is implicated in the development of both genetic and acquired epilepsies. Indeed, several causal mutations have been identified in patients with epilepsy, the most prominent of these being mutations in PTEN and tuberous sclerosis complexes 1 and 2 (TSC1, TSC2). These genes act as negative regulators of mTOR signaling, and mutations lead to hyperactivation of the pathway. Animal models deleting PTEN, TSC1, and TSC2 consistently produce epilepsy phenotypes, demonstrating that increased mTOR signaling can provoke neuronal hyperexcitability. Given the broad range of changes induced by altered mTOR signaling, however, the mechanisms underlying seizure development in these animals remain uncertain. In transgenic mice, cell populations with hyperactive mTOR have many structural abnormalities that support recurrent circuit formation, including somatic and dendritic hypertrophy, aberrant basal dendrites, and enlargement of axon tracts. At the functional level, mTOR hyperactivation is commonly, but not always, associated with enhanced synaptic transmission and plasticity. Moreover, these populations of abnormal neurons can affect the larger network, inducing secondary changes that may explain paradoxical findings reported between cell and network functioning in different models or at different developmental time points. Here, we review the animal literature examining the link between mTOR hyperactivation and epileptogenesis, emphasizing the impact of enhanced mTOR signaling on neuronal form and function.

Ventromedial hypothalamic neurons control a defensive emotion state

PubMed Central

Kunwar, Prabhat S; Zelikowsky, Moriel; Remedios, Ryan; Cai, Haijiang; Yilmaz, Melis; Meister, Markus; Anderson, David J

2015-01-01

Defensive behaviors reflect underlying emotion states, such as fear. The hypothalamus plays a role in such behaviors, but prevailing textbook views depict it as an effector of upstream emotion centers, such as the amygdala, rather than as an emotion center itself. We used optogenetic manipulations to probe the function of a specific hypothalamic cell type that mediates innate defensive responses. These neurons are sufficient to drive multiple defensive actions, and required for defensive behaviors in diverse contexts. The behavioral consequences of activating these neurons, moreover, exhibit properties characteristic of emotion states in general, including scalability, (negative) valence, generalization and persistence. Importantly, these neurons can also condition learned defensive behavior, further refuting long-standing claims that the hypothalamus is unable to support emotional learning and therefore is not an emotion center. These data indicate that the hypothalamus plays an integral role to instantiate emotion states, and is not simply a passive effector of upstream emotion centers. DOI: http://dx.doi.org/10.7554/eLife.06633.001 PMID:25748136

Einstein-Podolsky-Rosen paradox in single pairs of images.

PubMed

Lantz, Eric; Denis, Séverine; Moreau, Paul-Antoine; Devaux, Fabrice

2015-10-05

Spatially entangled twin photons provide a test of the Einstein-Podolsky-Rosen (EPR) paradox in its original form of position (image plane) versus impulsion (Fourier plane). We show that recording a single pair of images in each plane is sufficient to safely demonstrate an EPR paradox. On each pair of images, we have retrieved the fluctuations by subtracting the fitted deterministic intensity shape and then have obtained an intercorrelation peak with a sufficient signal to noise ratio to safely distinguish this peak from random fluctuations. A 95% confidence interval has been determined, confirming a high degree of paradox whatever the considered single pairs. Last, we have verified that the value of the variance of the difference between twin images is always below the quantum (poissonian) limit, in order to ensure the particle character of the demonstration. Our demonstration shows that a single image pattern can reveal the quantum and non-local behavior of light.

Teaching Quantum Physics without Paradoxes

ERIC Educational Resources Information Center

Hobson, Art

2007-01-01

Although the resolution to the wave-particle paradox has been known for 80 years, it is seldom presented. Briefly, the resolution is that material particles and photons are the quanta of extended spatially continuous but energetically quantized fields. But because the resolution resides in quantum field theory and is not usually spelled out in…

Cadherin-8 expression, synaptic localization, and molecular control of neuronal form in prefrontal corticostriatal circuits.

PubMed

Friedman, Lauren G; Riemslagh, Fréderike W; Sullivan, Josefa M; Mesias, Roxana; Williams, Frances M; Huntley, George W; Benson, Deanna L

2015-01-01

Neocortical interactions with the dorsal striatum support many motor and executive functions, and such underlying functional networks are particularly vulnerable to a variety of developmental, neurological, and psychiatric brain disorders, including autism spectrum disorders, Parkinson's disease, and Huntington's disease. Relatively little is known about the development of functional corticostriatal interactions, and in particular, virtually nothing is known of the molecular mechanisms that control generation of prefrontal cortex-striatal circuits. Here, we used regional and cellular in situ hybridization techniques coupled with neuronal tract tracing to show that Cadherin-8 (Cdh8), a homophilic adhesion protein encoded by a gene associated with autism spectrum disorders and learning disability susceptibility, is enriched within striatal projection neurons in the medial prefrontal cortex and in striatal medium spiny neurons forming the direct or indirect pathways. Developmental analysis of quantitative real-time polymerase chain reaction and western blot data show that Cdh8 expression peaks in the prefrontal cortex and striatum at P10, when cortical projections start to form synapses in the striatum. High-resolution immunoelectron microscopy shows that Cdh8 is concentrated at excitatory synapses in the dorsal striatum, and Cdh8 knockdown in cortical neurons impairs dendritic arborization and dendrite self-avoidance. Taken together, our findings indicate that Cdh8 delineates developing corticostriatal circuits where it is a strong candidate for regulating the generation of normal cortical projections, neuronal morphology, and corticostriatal synapses. © 2014 Wiley Periodicals, Inc.

The plasmasphere electron content paradox

NASA Astrophysics Data System (ADS)

Krall, J.; Huba, J. D.

2016-09-01

Measurements show that plasmasphere refilling rates decrease with increasing solar activity, while paradoxically, the vertical integration of the plasmasphere electron density (pTEC) increases with increasing solar activity. Using the Naval Research Laboratory SAMI2 (Sami2 is Another Model of the Ionosphere) and SAMI3 (Sami3 is Also a Model of the Ionosphere) codes, we simulate plasmasphere refilling following a model storm, reproducing this observed phenomenon. In doing so, we find that the refilling rate and resulting pTEC values are sensitive to the oxygen profile in the thermosphere and exosphere: the supply of H+ in the topside ionosphere is limited by the local O+ density, through H+O+→H++O charge exchange. At solar minimum, the O+ supply simply increases with the O density in the exosphere. At solar maximum, we find that O-O+ collisions limit the O+ density in the topside ionosphere such that it decreases with increasing O density. The paradox occurs because the pTEC metric gives electrons in the topside ionosphere more weight than electrons in the plasmasphere.

Mechanosensory neurons control sweet sensing in Drosophila

PubMed Central

Jeong, Yong Taek; Oh, Soo Min; Shim, Jaewon; Seo, Jeong Taeg; Kwon, Jae Young; Moon, Seok Jun

2016-01-01

Animals discriminate nutritious food from toxic substances using their sense of taste. Since taste perception requires taste receptor cells to come into contact with water-soluble chemicals, it is a form of contact chemosensation. Concurrent with that contact, mechanosensitive cells detect the texture of food and also contribute to the regulation of feeding. Little is known, however, about the extent to which chemosensitive and mechanosensitive circuits interact. Here, we show Drosophila prefers soft food at the expense of sweetness and that this preference requires labellar mechanosensory neurons (MNs) and the mechanosensory channel Nanchung. Activation of these labellar MNs causes GABAergic inhibition of sweet-sensing gustatory receptor neurons, reducing the perceived intensity of a sweet stimulus. These findings expand our understanding of the ways different sensory modalities cooperate to shape animal behaviour. PMID:27641708

Experimental test of the irreducible four-qubit Greenberger-Horne-Zeilinger paradox

NASA Astrophysics Data System (ADS)

Su, Zu-En; Tang, Wei-Dong; Wu, Dian; Cai, Xin-Dong; Yang, Tao; Li, Li; Liu, Nai-Le; Lu, Chao-Yang; Żukowski, Marek; Pan, Jian-Wei

2017-03-01

The paradox of Greenberger-Horne-Zeilinger (GHZ) disproves directly the concept of EPR elements of reality, based on the EPR correlations, in an all-versus-nothing way. A three-qubit experimental demonstration of the GHZ paradox was achieved nearly 20 years ago, followed by demonstrations for more qubits. Still, the GHZ contradictions underlying the tests can be reduced to a three-qubit one. We show an irreducible four-qubit GHZ paradox, and report its experimental demonstration. The bound of a three-setting-per-party Bell-GHZ inequality is violated by 7 σ . The fidelity of the GHZ state was around 81 % , and an entanglement witness reveals a violation of the separability threshold by 19 σ .

Fault-tolerant Greenberger-Horne-Zeilinger paradox based on non-Abelian anyons.

PubMed

Deng, Dong-Ling; Wu, Chunfeng; Chen, Jing-Ling; Oh, C H

2010-08-06

We propose a scheme to test the Greenberger-Horne-Zeilinger paradox based on braidings of non-Abelian anyons, which are exotic quasiparticle excitations of topological states of matter. Because topological ordered states are robust against local perturbations, this scheme is in some sense "fault-tolerant" and might close the detection inefficiency loophole problem in previous experimental tests of the Greenberger-Horne-Zeilinger paradox. In turn, the construction of the Greenberger-Horne-Zeilinger paradox reveals the nonlocal property of non-Abelian anyons. Our results indicate that the non-Abelian fractional statistics is a pure quantum effect and cannot be described by local realistic theories. Finally, we present a possible experimental implementation of the scheme based on the anyonic interferometry technologies.

Steering, Entanglement, Nonlocality, and the EPR Paradox

NASA Astrophysics Data System (ADS)

Wiseman, Howard; Jones, Steve; Andrew, Doherty

2007-06-01

The concept of steering was introduced by Schroedinger in 1935 as a generalization of the EPR paradox for arbitrary pure bipartite entangled states and arbitrary measurements by one party. Until now, it has never been rigorously defined, so it has not been known (for example) what mixed states are steerable (that is, can be used to exhibit steering). We provide an operational definition, from which we prove (by considering Werner states and Isotropic states) that steerable states are a strict subset of the entangled states, and a strict superset of the states that can exhibit Bell-nonlocality. For arbitrary bipartite Gaussian states we derive a linear matrix inequality that decides the question of steerability via Gaussian measurements, and we relate this to the original EPR paradox.

A Canadian paradox: Tommy Douglas and eugenics.

PubMed

Shevell, Michael

2012-01-01

Tommy Douglas is an icon of Canadian 20th Century political history and is considered by many as the "Father" of Medicare, a key component of our national identity. Throughout his career, he was associated at both the provincial and federal levels with progressive causes concerning disadvantaged populations. In his sociology Master's thesis written in the early 1930's, Douglas endorsed eugenic oriented solutions such as segregation and sterilization to address what was perceived to be an endemic and biologically determined problem. At first glance, this endorsement of eugenics appears to be paradoxical, but careful analysis revealed that this paradox has multiple roots in religion, political belief, historical exposure and our own desire to view our collective history in a favourable light.

Exercise-induced neuronal plasticity in central autonomic networks: role in cardiovascular control.

PubMed

Michelini, Lisete C; Stern, Javier E

2009-09-01

It is now well established that brain plasticity is an inherent property not only of the developing but also of the adult brain. Numerous beneficial effects of exercise, including improved memory, cognitive function and neuroprotection, have been shown to involve an important neuroplastic component. However, whether major adaptive cardiovascular adjustments during exercise, needed to ensure proper blood perfusion of peripheral tissues, also require brain neuroplasticity, is presently unknown. This review will critically evaluate current knowledge on proposed mechanisms that are likely to underlie the continuous resetting of baroreflex control of heart rate during/after exercise and following exercise training. Accumulating evidence indicates that not only somatosensory afferents (conveyed by skeletal muscle receptors, baroreceptors and/or cardiopulmonary receptors) but also projections arising from central command neurons (in particular, peptidergic hypothalamic pre-autonomic neurons) converge into the nucleus tractus solitarii (NTS) in the dorsal brainstem, to co-ordinate complex cardiovascular adaptations during dynamic exercise. This review focuses in particular on a reciprocally interconnected network between the NTS and the hypothalamic paraventricular nucleus (PVN), which is proposed to act as a pivotal anatomical and functional substrate underlying integrative feedforward and feedback cardiovascular adjustments during exercise. Recent findings supporting neuroplastic adaptive changes within the NTS-PVN reciprocal network (e.g. remodelling of afferent inputs, structural and functional neuronal plasticity and changes in neurotransmitter content) will be discussed within the context of their role as important underlying cellular mechanisms supporting the tonic activation and improved efficacy of these central pathways in response to circulatory demand at rest and during exercise, both in sedentary and in trained individuals. We hope this review will stimulate

Speed and segmentation control mechanisms characterized in rhythmically-active circuits created from spinal neurons produced from genetically-tagged embryonic stem cells

PubMed Central

Sternfeld, Matthew J; Hinckley, Christopher A; Moore, Niall J; Pankratz, Matthew T; Hilde, Kathryn L; Driscoll, Shawn P; Hayashi, Marito; Amin, Neal D; Bonanomi, Dario; Gifford, Wesley D; Sharma, Kamal; Goulding, Martyn; Pfaff, Samuel L

2017-01-01

Flexible neural networks, such as the interconnected spinal neurons that control distinct motor actions, can switch their activity to produce different behaviors. Both excitatory (E) and inhibitory (I) spinal neurons are necessary for motor behavior, but the influence of recruiting different ratios of E-to-I cells remains unclear. We constructed synthetic microphysical neural networks, called circuitoids, using precise combinations of spinal neuron subtypes derived from mouse stem cells. Circuitoids of purified excitatory interneurons were sufficient to generate oscillatory bursts with properties similar to in vivo central pattern generators. Inhibitory V1 neurons provided dual layers of regulation within excitatory rhythmogenic networks - they increased the rhythmic burst frequency of excitatory V3 neurons, and segmented excitatory motor neuron activity into sub-networks. Accordingly, the speed and pattern of spinal circuits that underlie complex motor behaviors may be regulated by quantitatively gating the intra-network cellular activity ratio of E-to-I neurons. DOI: http://dx.doi.org/10.7554/eLife.21540.001 PMID:28195039

Introducing the Levinthal's Protein Folding Paradox and Its Solution

ERIC Educational Resources Information Center

Martínez, Leandro

2014-01-01

The protein folding (Levinthal's) paradox states that it would not be possible in a physically meaningful time to a protein to reach the native (functional) conformation by a random search of the enormously large number of possible structures. This paradox has been solved: it was shown that small biases toward the native conformation result…

The Use of Paradoxical Intention in the Treatment of Panic Attacks.

ERIC Educational Resources Information Center

Dattilio, Frank M.

1987-01-01

Discusses the counseling use of paradoxical intention, in which clients are told to perform responses that seem incompatible with the goal for which they are seeking help. The use of paradoxical intention in the treatment of panic attacks is described and a case example is included. The nature and implementation of the technique are discussed.…

Facing Paradox Everyday: A Heideggerian Approach to the Ethics of Teaching

ERIC Educational Resources Information Center

d'Agnese, Vasco

2016-01-01

In this paper, I wish to offer insight into the role of paradox in teaching. I will do so by analyzing teachers' everyday work, taking a qualitative approach and constructing a small-scale empirical study. Philosophically, my attempt is framed by Heidegger's thought. Drawing from research data, I argue the following: (a) paradoxes and dilemmas are…

Autonomic control network active in Aplysia during locomotion includes neurons that express splice variants of R15-neuropeptides.

PubMed

Romanova, Elena V; McKay, Natasha; Weiss, Klaudiusz R; Sweedler, Jonathan V; Koester, John

2007-01-01

Splice-variant products of the R15 neuropeptide gene are differentially expressed within the CNS of Aplysia. The goal of this study was to test whether the neurons in the abdominal ganglion that express the peptides encoded by this gene are part of a common circuit. Expression of R15 peptides had been demonstrated previously in neuron R15. Using a combination of immunocytochemical and analytical methods, this study demonstrated that R15 peptides are also expressed in heart exciter neuron RB(HE), the two L9(G) gill motoneurons, and L40--a newly identified interneuron. Mass spectrometric profiling of individual neurons that exhibit R15 peptide-like immunoreactivity confirmed the mutually exclusive expression of two splice-variant forms of R15 peptides in different neurons. The L9(G) cells were found to co-express pedal peptide in addition to the R15 peptides. The R15 peptide-expressing neurons examined here were shown to be part of an autonomic control circuit that is active during fictive locomotion. Activity in this circuit contributes to implementing a central command that may help to coordinate autonomic activity with escape locomotion. Chronic extracellular nerve recording was used to determine the activity patterns of a subset of neurons of this circuit in vivo. These results demonstrate the potential utility of using shared patterns of neuropeptide expression as a guide for neural circuit identification.

Regulatory logic of pan-neuronal gene expression in C. elegans

PubMed Central

Stefanakis, Nikolaos; Carrera, Ines; Hobert, Oliver

2015-01-01

While neuronal cell types display an astounding degree of phenotypic diversity, most if not all neuron types share a core panel of terminal features. However, little is known about how pan-neuronal expression patterns are genetically programmed. Through an extensive analysis of the cis-regulatory control regions of a battery of pan-neuronal C.elegans genes, including genes involved in synaptic vesicle biology and neuropeptide signaling, we define a common organizational principle in the regulation of pan-neuronal genes in the form of a surprisingly complex array of seemingly redundant, parallel-acting cis-regulatory modules that direct expression to broad, overlapping domains throughout the nervous system. These parallel-acting cis-regulatory modules are responsive to a multitude of distinct trans-acting factors. Neuronal gene expression programs therefore fall into two fundamentally distinct classes. Neuron type-specific genes are generally controlled by discrete and non-redundantly acting regulatory inputs, while pan-neuronal gene expression is controlled by diverse, coincident and seemingly redundant regulatory inputs. PMID:26291158

Hypothalamic neurones governing glucose homeostasis.

PubMed

Coppari, R

2015-06-01

The notion that the brain directly controls the level of glucose in the blood (glycaemia) independent of its known action on food intake and body weight has been known ever since 1849. That year, the French physiologist Dr Claude Bernard reported that physical puncture of the floor of the fourth cerebral ventricle rapidly leads to an increased level of sugar in the blood (and urine) in rabbits. Despite this important discovery, it took approximately 150 years before significant efforts aimed at understanding the underlying mechanism of brain-mediated control of glucose metabolism were made. Technological developments allowing for genetically-mediated manipulation of selected molecular pathways in a neurone-type-specific fashion unravelled the importance of specific molecules in specific neuronal populations. These neuronal pathways govern glucose metabolism in the presence and even in the absence of insulin. Also, a peculiarity of these pathways is that certain biochemically-defined neurones govern glucose metabolism in a tissue-specific fashion. © 2015 British Society for Neuroendocrinology.

The Paradox of Painful Art

ERIC Educational Resources Information Center

Smuts, Aaron

2007-01-01

Many of the most popular genres of narrative art are designed to elicit negative emotions: emotions that are experienced as painful or involving some degree of pain, which people generally avoid in their daily lives. Traditionally, the question of why people seek out such experiences of painful art has been presented as the paradox of tragedy, and…

Mechanical Paradox: The Uphill Roller

ERIC Educational Resources Information Center

Cortes, Emilio; Cortes-Poza, D.

2011-01-01

We analyse in detail the dynamics of a mechanical system which is a rigid body with the geometry of a double cone. This double cone is apparently able to spontaneously roll uphill along inclined rails. The experiment has been known for some centuries, and because of its peculiar behaviour, it has been named "mechanical paradox". Although this…

CCC and the Fermi paradox

NASA Astrophysics Data System (ADS)

Gurzadyan, V. G.; Penrose, R.

2016-01-01

Within the scheme of conformal cyclic cosmology (CCC), information can be transmitted from aeon to aeon. Accordingly, the "Fermi paradox" and the SETI programme --of communication by remote civilizations-- may be examined from a novel perspective: such information could, in principle, be encoded in the cosmic microwave background. The current empirical status of CCC is also discussed.

MCM Paradox: Abundance of Eukaryotic Replicative Helicases and Genomic Integrity

PubMed Central

Das, Mitali; Singh, Sunita; Pradhan, Satyajit

2014-01-01

As a crucial component of DNA replication licensing system, minichromosome maintenance (MCM) 2–7 complex acts as the eukaryotic DNA replicative helicase. The six related MCM proteins form a heterohexamer and bind with ORC, CDC6, and Cdt1 to form the prereplication complex. Although the MCMs are well known as replicative helicases, their overabundance and distribution patterns on chromatin present a paradox called the “MCM paradox.” Several approaches had been taken to solve the MCM paradox and describe the purpose of excess MCMs distributed beyond the replication origins. Alternative functions of these MCMs rather than a helicase had also been proposed. This review focuses on several models and concepts generated to solve the MCM paradox coinciding with their helicase function and provides insight into the concept that excess MCMs are meant for licensing dormant origins as a backup during replication stress. Finally, we extend our view towards the effect of alteration of MCM level. Though an excess MCM constituent is needed for normal cells to withstand stress, there must be a delineation of the threshold level in normal and malignant cells. This review also outlooks the future prospects to better understand the MCM biology. PMID:25386362

The upregulation of specific interleukin (IL) receptor antagonists and paradoxical enhancement of neuronal apoptosis due to electrode induced strain and brain micromotion.

PubMed

Karumbaiah, Lohitash; Norman, Sharon E; Rajan, Nithish B; Anand, Sanjay; Saxena, Tarun; Betancur, Martha; Patkar, Radhika; Bellamkonda, Ravi V

2012-09-01

The high mechanical mismatch between stiffness of silicon and metal microelectrodes and soft cortical tissue, induces strain at the neural interface which likely contributes to failure of the neural interface. However, little is known about the molecular outcomes of electrode induced low-magnitude strain (1-5%) on primary astrocytes, microglia and neurons. In this study we simulated brain micromotion at the electrode-brain interface by subjecting astrocytes, microglia and primary cortical neurons to low-magnitude cyclical strain using a biaxial stretch device, and investigated the molecular outcomes of induced strain in vitro. In addition, we explored the functional consequence of astrocytic and microglial strain on neural health, when they are themselves subjected to strain. Quantitative real-time PCR array (qRT-PCR Array) analysis of stretched astrocytes and microglia showed strain specific upregulation of an Interleukin receptor antagonist - IL-36Ra (previously IL-1F5), to ≈ 1018 and ≈ 236 fold respectively. Further, IL-36Ra gene expression remained unchanged in astrocytes and microglia treated with bacterial lipopolysaccharide (LPS) indicating that the observed upregulation in stretched astrocytes and microglia is potentially strain specific. Zymogram and western blot analysis revealed that mechanically strained astrocytes and microglia upregulated matrix metalloproteinases (MMPs) 2 and 9, and other markers of reactive gliosis such as glial fibrillary acidic protein (GFAP) and neurocan when compared to controls. Primary cortical neurons when stretched with and without IL-36Ra, showed a ≈ 400 fold downregulation of tumor necrosis factor receptor superfamily, member 11b (TNFRSF11b). Significant upregulation of members of the caspase cysteine proteinase family and other pro-apoptotic genes was also observed in the presence of IL-36Ra than in the absence of IL-36Ra. Adult rats when implanted with microwire electrodes showed upregulation of IL-36Ra (≈ 20

Neuronal machinery of sleep homeostasis in Drosophila.

PubMed

Donlea, Jeffrey M; Pimentel, Diogo; Miesenböck, Gero

2014-02-19

Sleep is under homeostatic control, but the mechanisms that sense sleep need and correct sleep deficits remain unknown. Here, we report that sleep-promoting neurons with projections to the dorsal fan-shaped body (FB) form the output arm of Drosophila's sleep homeostat. Homeostatic sleep control requires the Rho-GTPase-activating protein encoded by the crossveinless-c (cv-c) gene in order to transduce sleep pressure into increased electrical excitability of dorsal FB neurons. cv-c mutants exhibit decreased sleep time, diminished sleep rebound, and memory deficits comparable to those after sleep loss. Targeted ablation and rescue of Cv-c in sleep-control neurons of the dorsal FB impair and restore, respectively, normal sleep patterns. Sleep deprivation increases the excitability of dorsal FB neurons, but this homeostatic adjustment is disrupted in short-sleeping cv-c mutants. Sleep pressure thus shifts the input-output function of sleep-promoting neurons toward heightened activity by modulating ion channel function in a mechanism dependent on Cv-c. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Temperature manipulation of neuronal dynamics in a forebrain motor control nucleus

PubMed Central

Mindlin, Gabriel B.

2017-01-01

Different neuronal types within brain motor areas contribute to the generation of complex motor behaviors. A widely studied songbird forebrain nucleus (HVC) has been recognized as fundamental in shaping the precise timing characteristics of birdsong. This is based, among other evidence, on the stretching and the “breaking” of song structure when HVC is cooled. However, little is known about the temperature effects that take place in its neurons. To address this, we investigated the dynamics of HVC both experimentally and computationally. We developed a technique where simultaneous electrophysiological recordings were performed during temperature manipulation of HVC. We recorded spontaneous activity and found three effects: widening of the spike shape, decrease of the firing rate and change in the interspike interval distribution. All these effects could be explained with a detailed conductance based model of all the neurons present in HVC. Temperature dependence of the ionic channel time constants explained the first effect, while the second was based in the changes of the maximal conductance using single synaptic excitatory inputs. The last phenomenon, only emerged after introducing a more realistic synaptic input to the inhibitory interneurons. Two timescales were present in the interspike distributions. The behavior of one timescale was reproduced with different input balances received form the excitatory neurons, whereas the other, which disappears with cooling, could not be found assuming poissonian synaptic inputs. Furthermore, the computational model shows that the bursting of the excitatory neurons arises naturally at normal brain temperature and that they have an intrinsic delay at low temperatures. The same effect occurs at single synapses, which may explain song stretching. These findings shed light on the temperature dependence of neuronal dynamics and present a comprehensive framework to study neuronal connectivity. This study, which is based on

Optogenetic identification of hypothalamic orexin neuron projections to paraventricular spinally projecting neurons.

PubMed

Dergacheva, Olga; Yamanaka, Akihiro; Schwartz, Alan R; Polotsky, Vsevolod Y; Mendelowitz, David

2017-04-01

Orexin neurons, and activation of orexin receptors, are generally thought to be sympathoexcitatory; however, the functional connectivity between orexin neurons and a likely sympathetic target, the hypothalamic spinally projecting neurons (SPNs) in the paraventricular nucleus of the hypothalamus (PVN) has not been established. To test the hypothesis that orexin neurons project directly to SPNs in the PVN, channelrhodopsin-2 (ChR2) was selectively expressed in orexin neurons to enable photoactivation of ChR2-expressing fibers while examining evoked postsynaptic currents in SPNs in rat hypothalamic slices. Selective photoactivation of orexin fibers elicited short-latency postsynaptic currents in all SPNs tested ( n = 34). These light-triggered responses were heterogeneous, with a majority being excitatory glutamatergic responses (59%) and a minority of inhibitory GABAergic (35%) and mixed glutamatergic and GABAergic currents (6%). Both glutamatergic and GABAergic responses were present in the presence of tetrodotoxin and 4-aminopyridine, suggesting a monosynaptic connection between orexin neurons and SPNs. In addition to generating postsynaptic responses, photostimulation facilitated action potential firing in SPNs (current clamp configuration). Glutamatergic, but not GABAergic, postsynaptic currents were diminished by application of the orexin receptor antagonist almorexant, indicating orexin release facilitates glutamatergic neurotransmission in this pathway. This work identifies a neuronal circuit by which orexin neurons likely exert sympathoexcitatory control of cardiovascular function. NEW & NOTEWORTHY This is the first study to establish, using innovative optogenetic approaches in a transgenic rat model, that there are robust heterogeneous projections from orexin neurons to paraventricular spinally projecting neurons, including excitatory glutamatergic and inhibitory GABAergic neurotransmission. Endogenous orexin release modulates glutamatergic, but not

The rapid reproducers paradox: population control and individual procreative rights.

PubMed

Wissenburg, M

1998-01-01

This article argues that population policies need to be evaluated from macro and micro perspectives and to consider individual rights. Ecological arguments that are stringent conditions of liberal democracy are assessed against a moral standard. The moral standard is applied to a series of reasons for limiting procreative rights in the cause of sustainability. The focus is directly on legally enforced antinatalist measures and not on indirect policies with incentives and disincentives. The explicit assumption is that population policy violates the fairness to individuals for societal gain and that population policies are incompatible with stringent conditions of liberal democracy. The author identifies the individual-societal tradeoff as the "rapid reproducers paradox." The perfect sustainable population level is either not possible or is a repugnant alternative. 12 ecological arguments are presented, and none are found compatible with notions of a liberal democracy. Three alternative antinatalist options are the acceptance of less rigid and still coercive policies, amendments to the conception of liberal democracy, or loss of hope and choice of noncoercive solutions to sustainability, none of which is found viable. If voluntary abstinence and distributive solutions fail, then frugal demand options and technological supply options both will be necessary.

A Probabilistic Analysis of the Fermi Paradox

NASA Astrophysics Data System (ADS)

Solomonides, Evan; Terzian, Yervant

2016-06-01

The Fermi paradox uses an appeal to the mediocrity principle to make it seem counterintuitive that humanity has not been contacted by extraterrestrial intelligence. A numerical, statistical analysis was conducted to determine whether this apparent loneliness is, in fact, unexpected. An inequality was derived to relate the frequency of life arising and developing technology on a suitable planet in the galaxy; the average length of time since the first broadcast of such a civilization; and a constant term. An analysis of the sphere reached thus far by human communication was also conducted, considering our local neighborhood and planets of particular interest. These analyses both conclude that the Fermi paradox is not, in fact, unexpected. By the mediocrity principle and numerical modeling, it is actually unlikely that the Earth would have been reached by extraterrestrial communication at this point. We predict that under 1% of the galaxy has been reached at all thus far, and we do not anticipate to be reached until approximately 50% of stars/planets have been reached. We offer a prediction that we should not expect this until at least 1,500 years in the future. Thus the Fermi paradox is not a shocking observation- or lack thereof- and humanity may very well be contacted within our species’ lifespan (we can begin to expect to be contacted 1,500 years in the future).

Obesity and poverty paradox in developed countries.

PubMed

Żukiewicz-Sobczak, Wioletta; Wróblewska, Paula; Zwoliński, Jacek; Chmielewska-Badora, Jolanta; Adamczuk, Piotr; Krasowska, Ewelina; Zagórski, Jerzy; Oniszczuk, Anna; Piątek, Jacek; Silny, Wojciech

2014-01-01

Obesity is a civilization disease and the proportion of people suffering from it continues to grow, especially in the developed countries. Number of obese people in Europe has increased threefold over the last 20 years. The paradox of obesity and poverty relationship is observed especially in the developed and developing countries. In developing countries, along with economic development and income growth, the number of people with overweight and obesity is increasing. This paradox has a relationship with both the easy availability and low cost of highly processed foods containing 'empty calories' and no nutritional value. To date, this paradox has been described in the United States and the United Kingdom, although many European countries are also experiencing high percentages of obese people. Among the reasons for the growing obesity in the population of poor people are: higher unemployment, lower education level, and irregular meals. Another cause of obesity is low physical activity, which among the poor is associated with a lack of money for sports equipment. Due to the large rate of deaths caused by diseases directly linked to obesity, the governments of many countries implement prevention programmes of overweight and obesity. These programmes are based primarily on educating the public about a healthy lifestyle based on healthy eating, daily physical activity and avoiding alcohol and cigarettes.

Sensory neurons do not induce motor neuron loss in a human stem cell model of spinal muscular atrophy.

PubMed

Schwab, Andrew J; Ebert, Allison D

2014-01-01

Spinal muscular atrophy (SMA) is an autosomal recessive disorder leading to paralysis and early death due to reduced SMN protein. It is unclear why there is such a profound motor neuron loss, but recent evidence from fly and mouse studies indicate that cells comprising the whole sensory-motor circuit may contribute to motor neuron dysfunction and loss. Here, we used induced pluripotent stem cells derived from SMA patients to test whether sensory neurons directly contribute to motor neuron loss. We generated sensory neurons from SMA induced pluripotent stem cells and found no difference in neuron generation or survival, although there was a reduced calcium response to depolarizing stimuli. Using co-culture of SMA induced pluripotent stem cell derived sensory neurons with control induced pluripotent stem cell derived motor neurons, we found no significant reduction in motor neuron number or glutamate transporter boutons on motor neuron cell bodies or neurites. We conclude that SMA sensory neurons do not overtly contribute to motor neuron loss in this human stem cell system.

[The detector, the command neuron and plastic convergence].

PubMed

Sokolov, E N

1977-01-01

The paper deals with the structure of detectors, the function of commanding neurones and the problem of relationship between detectors and commanding neurons. An example of hierarchial organization of detectors is provided by the colour analyser in which a layer of receptors, a layer of opponent neurones and a layer of colour-selective detectors are singled out. The colour detector is selectively sensitive to a certain combination of excitations at the input. If the detector is selectively activated by a certain combination of excitations at the input, the selective activation of the commanding neurone through a pool of motoneurones brings about a reaction at the output, specific in its organization. The reflexogenic zone of the reaction is determined by the detectors which converge on the commanding neurone controlling the given reaction. The plasticity of the reaction results from a plastic convergence of the detectors on the commanding neurone which controls the reaction. This comprises selective switching off the detectors from the commanding neurone (habituation) and connecting the detectors to the commanding neurone (facilitation).

Space Curvature and the "Heavy Banana 'Paradox.'"

ERIC Educational Resources Information Center

Gruber, Ronald P.; And Others

1991-01-01

Two ways to visually enhance the concept of space curvature are described. Viewing space curvature as a meterstick contraction and the heavy banana "paradox" are discussed. The meterstick contraction is mathematically explained. (KR)

Genetic activation, inactivation and deletion reveal a limited and nuanced role for somatostatin-containing basal forebrain neurons in behavioral state control.

PubMed

Anaclet, Christelle; De Luca, Roberto; Venner, Anne; Malyshevskaya, Olga; Lazarus, Michael; Arrigoni, Elda; Fuller, Patrick M

2018-05-07

Recent studies have identified an especially important role for basal forebrain GABAergic (BF VGAT ) neurons in the regulation of behavioral waking and fast cortical rhythms associated with cognition. However, BF VGAT neurons comprise several neurochemically and anatomically distinct sub-populations, including parvalbumin- and somatostatin-containing BF VGAT neurons (BF Parv and BF SOM ), and it was recently reported that optogenetic activation of BF SOM neurons increases the probability of a wakefulness to non-rapid-eye movement (NREM) sleep transition when stimulated during the animal's rest period. This finding was unexpected given that most BF SOM neurons are not NREM sleep active and that central administration of the synthetic SOM analog, octreotide, suppresses NREM sleep or increases REM sleep. Here we employed a combination of genetically-driven chemogenetic and optogenetic activation, chemogenetic inhibition and ablation approaches to further explore the in vivo role of BF SOM neurons in arousal control. Our findings indicate that acute activation or inhibition of BF SOM neurons is neither wakefulness- nor NREM sleep-promoting, is without significant effect on the EEG, and that chronic loss of these neurons is without effect on total 24h sleep amounts, although a small but significant increase in waking was observed in the lesioned mice during the early active period. Our in vitro cell recordings further reveal electrophysiological heterogeneity in BF SOM neurons, specifically suggesting at least two distinct sub-populations. Taken together our data support the more nuanced view that BF SOM are electrically heterogeneous and are not NREM sleep- or wake-promoting per se , but may exert, in particular during the early active period, a modest inhibitory influence on arousal circuitry. SIGNIFICANCE STATEMENT The cellular basal forebrain (BF) is a highly complex area of the brain that is implicated in a wide-range of higher-level neurobiological processes

Matrix stiffness modulates formation and activity of neuronal networks of controlled architectures.

PubMed

Lantoine, Joséphine; Grevesse, Thomas; Villers, Agnès; Delhaye, Geoffrey; Mestdagh, Camille; Versaevel, Marie; Mohammed, Danahe; Bruyère, Céline; Alaimo, Laura; Lacour, Stéphanie P; Ris, Laurence; Gabriele, Sylvain

2016-05-01

The ability to construct easily in vitro networks of primary neurons organized with imposed topologies is required for neural tissue engineering as well as for the development of neuronal interfaces with desirable characteristics. However, accumulating evidence suggests that the mechanical properties of the culture matrix can modulate important neuronal functions such as growth, extension, branching and activity. Here we designed robust and reproducible laminin-polylysine grid micropatterns on cell culture substrates that have similar biochemical properties but a 100-fold difference in Young's modulus to investigate the role of the matrix rigidity on the formation and activity of cortical neuronal networks. We found that cell bodies of primary cortical neurons gradually accumulate in circular islands, whereas axonal extensions spread on linear tracks to connect circular islands. Our findings indicate that migration of cortical neurons is enhanced on soft substrates, leading to a faster formation of neuronal networks. Furthermore, the pre-synaptic density was two times higher on stiff substrates and consistently the number of action potentials and miniature synaptic currents was enhanced on stiff substrates. Taken together, our results provide compelling evidence to indicate that matrix stiffness is a key parameter to modulate the growth dynamics, synaptic density and electrophysiological activity of cortical neuronal networks, thus providing useful information on scaffold design for neural tissue engineering. Copyright © 2016 Elsevier Ltd. All rights reserved.

Motivational Modulation of Self-Initiated and Externally Triggered Movement Speed Induced by Threat of Shock: Experimental Evidence for Paradoxical Kinesis in Parkinson’s Disease

PubMed Central

McDonald, Louise M.; Griffin, Harry J.; Angeli, Aikaterini; Torkamani, Mariam; Georgiev, Dejan; Jahanshahi, Marjan

2015-01-01

Background Paradoxical kinesis has been observed in bradykinetic people with Parkinson’s disease. Paradoxical kinesis occurs in situations where an individual is strongly motivated or influenced by relevant external cues. Our aim was to induce paradoxical kinesis in the laboratory. We tested whether the motivation of avoiding a mild electric shock was sufficient to induce paradoxical kinesis in externally-triggered and self-initiated conditions in people with Parkinson’s disease tested on medication and in age-matched controls. Methods Participants completed a shock avoidance behavioural paradigm in which half of the trials could result in a mild electric shock if the participant did not move fast enough. Half of the trials of each type were self-initiated and half were externally-triggered. The criterion for avoiding shock was a maximum movement time, adjusted according to each participant’s performance on previous trials using a staircase tracking procedure. Results On trials with threat of shock, both patients with Parkinson’s disease and controls had faster movement times compared to no potential shock trials, in both self-initiated and externally-triggered conditions. The magnitude of improvement of movement time from no potential shock to potential shock trials was positively correlated with anxiety ratings. Conclusions When motivated to avoid mild electric shock, patients with Parkinson’s disease, similar to healthy controls, showed significant speeding of movement execution. This was observed in both self-initiated and externally-triggered versions of the task. Nevertheless, in the ET condition the improvement of reaction times induced by motivation to avoid shocks was greater for the PD patients than controls, highlighting the value of external cues for movement initiation in PD patients. The magnitude of improvement from the no potential shock to the potential shock trials was associated with the threat-induced anxiety. This demonstration of

The RNA helicase DDX17 controls the transcriptional activity of REST and the expression of proneural microRNAs in neuronal differentiation.

PubMed

Lambert, Marie-Pierre; Terrone, Sophie; Giraud, Guillaume; Benoit-Pilven, Clara; Cluet, David; Combaret, Valérie; Mortreux, Franck; Auboeuf, Didier; Bourgeois, Cyril F

2018-06-21

The Repressor Element 1-silencing transcription factor (REST) represses a number of neuronal genes in non-neuronal cells or in undifferentiated neural progenitors. Here, we report that the DEAD box RNA helicase DDX17 controls important REST-related processes that are critical during the early phases of neuronal differentiation. First, DDX17 associates with REST, promotes its binding to the promoter of a subset of REST-targeted genes and co-regulates REST transcriptional repression activity. During neuronal differentiation, we observed a downregulation of DDX17 along with that of the REST complex that contributes to the activation of neuronal genes. Second, DDX17 and its paralog DDX5 regulate the expression of several proneural microRNAs that are known to target the REST complex during neurogenesis, including miR-26a/b that are also direct regulators of DDX17 expression. In this context, we propose a new mechanism by which RNA helicases can control the biogenesis of intronic miRNAs. We show that the processing of the miR-26a2 precursor is dependent on RNA helicases, owing to an intronic regulatory region that negatively impacts on both miRNA processing and splicing of its host intron. Our work places DDX17 in the heart of a pathway involving REST and miRNAs that allows neuronal gene repression.

Effect of systemic morphine on the responses of convergent neurons to noxious heat stimuli applied over graded surface areas.

PubMed

Gall, O; Bouhassira, D; Chitour, D; Le Bars, D

1999-04-01

Stimulus intensity is a major determinant of the antinociceptive activity of opiates. This study focused on the influence of the spatial characteristics of nociceptive stimuli, on opiate-induced depressions of nociceptive transmission at the level of the spinal cord. Anesthetized rats were prepared to allow extracellular recordings to be made from convergent neurons in the lumbar dorsal horn. The effects of systemic morphine (1 and 10 mg/kg) were compared with those of saline for thermal stimuli of constant intensity, applied to the area of skin surrounding the excitatory receptive field (1.9 cm2) or to a much larger adjacent area (18 cm2). The responses (mean +/- SD) elicited by the 1.9-cm2 stimulus were not modified by 1 mg/kg intravenous morphine, although they were decreased by the 10-mg/kg dose (to 11+/-4% of control values compared with saline; P < 0.05). In contrast, when the 18-cm2 stimulus was applied, 1 mg/kg intravenous morphine produced a paradoxical facilitation of the neuronal responses (159+/-36% of control values; P < 0.05) and 10 mg/kg intravenous morphine resulted in a weaker depression of the responses (to 42+/-24% of control values; P < 0.05) than was observed with the smaller stimulus. Doses of systemic morphine in the analgesic range for rats had dual effects on nociceptive transmission at the level of the spinal cord, depending on the surface area that was stimulated. Such effects are difficult to explain in terms of accepted pharmacodynamic concepts and may reflect an opioid-induced depression of descending inhibitory influences triggered by spatial summation.

Optimal GHZ Paradox for Three Qubits

NASA Astrophysics Data System (ADS)

Ren, Changliang; Su, Hong-Yi; Xu, Zhen-Peng; Wu, Chunfeng; Chen, Jing-Ling

2015-08-01

Quatum nonlocality as a valuable resource is of vital importance in quantum information processing. The characterization of the resource has been extensively investigated mainly for pure states, while relatively less is know for mixed states. Here we prove the existence of the optimal GHZ paradox by using a novel and simple method to extract an optimal state that can saturate the tradeoff relation between quantum nonlocality and the state purity. In this paradox, the logical inequality which is formulated by the GHZ-typed event probabilities can be violated maximally by the optimal state for any fixed amount of purity (or mixedness). Moreover, the optimal state can be described as a standard GHZ state suffering flipped color noise. The maximal amount of noise that the optimal state can resist is 50%. We suggest our result to be a step toward deeper understanding of the role played by the AVN proof of quantum nonlocality as a useful physical resource.

Control of Phasic Firing by a Background Leak Current in Avian Forebrain Auditory Neurons

PubMed Central

Dagostin, André A.; Lovell, Peter V.; Hilscher, Markus M.; Mello, Claudio V.; Leão, Ricardo M.

2015-01-01

Central neurons express a variety of neuronal types and ion channels that promote firing heterogeneity among their distinct neuronal populations. Action potential (AP) phasic firing, produced by low-threshold voltage-activated potassium currents (VAKCs), is commonly observed in mammalian brainstem neurons involved in the processing of temporal properties of the acoustic information. The avian caudomedial nidopallium (NCM) is an auditory area analogous to portions of the mammalian auditory cortex that is involved in the perceptual discrimination and memorization of birdsong and shows complex responses to auditory stimuli We performed in vitro whole-cell patch-clamp recordings in brain slices from adult zebra finches (Taeniopygia guttata) and observed that half of NCM neurons fire APs phasically in response to membrane depolarizations, while the rest fire transiently or tonically. Phasic neurons fired APs faster and with more temporal precision than tonic and transient neurons. These neurons had similar membrane resting potentials, but phasic neurons had lower membrane input resistance and time constant. Surprisingly phasic neurons did not express low-threshold VAKCs, which curtailed firing in phasic mammalian brainstem neurons, having similar VAKCs to other NCM neurons. The phasic firing was determined not by VAKCs, but by the potassium background leak conductances, which was more prominently expressed in phasic neurons, a result corroborated by pharmacological, dynamic-clamp, and modeling experiments. These results reveal a new role for leak currents in generating firing diversity in central neurons. PMID:26696830

Seasonal neuronal plasticity in song-control and auditory forebrain areas in subtropical nonmigratory and palearctic-indian migratory male songbirds.

PubMed

Surbhi; Rastogi, Ashutosh; Malik, Shalie; Rani, Sangeeta; Kumar, Vinod

2016-10-01

This study examines whether differences in annual life-history states (LHSs) among the inhabitants of two latitudes would have an impact on the neuronal plasticity of the song-control system in songbirds. At the times of equinoxes and solstices during the year (n = 4 per year) corresponding to different LHSs, we measured the volumetric changes and expression of doublecortin (DCX; an endogenous marker of the neuronal recruitment) in the song-control nuclei and higher order auditory forebrain regions of the subtropical resident Indian weaverbirds (Ploceus philippinus) and Palearctic-Indian migratory redheaded buntings (Emberiza bruniceps). Area X in basal ganglia, lateral magnocellular nucleus of the anterior nidopallium (LMAN), HVC (proper name), and robust nucleus of the arcopallium (RA) were enlarged during the breeding LHS. Both round and fusiform DCX-immunoreactive (DCX-ir) cells were found in area X and HVC but not in LMAN or RA, with a significant seasonal difference. Also, as shown by increase in volume and by dense, round DCX-ir cells, the neuronal incorporation was increased in HVC alone during the breeding LHS. This suggests differences in the response of song-control nuclei to photoperiod-induced changes in LHSs. Furthermore, DCX immunoreactivity indicated participation of the cortical caudomedial nidopallium and caudomedial mesopallium in the song-control system, albeit with differences between the weaverbirds and the buntings. Overall, these results show seasonal neuronal plasticity in the song-control system closely associated with annual reproductive LHS in both of the songbirds. Differences between species probably account for the differences in the photoperiod-response system between the relative refractory weaverbirds and absolute refractory redheaded buntings. J. Comp. Neurol. 524:2914-2929, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Damage to Arousal-Promoting Brainstem Neurons with Traumatic Brain Injury.

PubMed

Valko, Philipp O; Gavrilov, Yuri V; Yamamoto, Mihoko; Noaín, Daniela; Reddy, Hasini; Haybaeck, Johannes; Weis, Serge; Baumann, Christian R; Scammell, Thomas E

2016-06-01

Coma and chronic sleepiness are common after traumatic brain injury (TBI). Here, we explored whether injury to arousal-promoting brainstem neurons occurs in patients with fatal TBI. Postmortem examination of 8 TBI patients and 10 controls. Compared to controls, TBI patients had 17% fewer serotonergic neurons in the dorsal raphe nucleus (effect size: 1.25), but the number of serotonergic neurons did not differ in the median raphe nucleus. TBI patients also had 29% fewer noradrenergic neurons in the locus coeruleus (effect size: 0.96). The number of cholinergic neurons in the pedunculopontine and laterodorsal tegmental nuclei (PPT/LDT) was similar in TBI patients and controls. TBI injures arousal-promoting neurons of the mesopontine tegmentum, but this injury is less severe than previously observed in hypothalamic arousal-promoting neurons. Most likely, posttraumatic arousal disturbances are not primarily caused by damage to these brainstem neurons, but arise from an aggregate of injuries, including damage to hypothalamic arousal nuclei and disruption of other arousal-related circuitries. © 2016 Associated Professional Sleep Societies, LLC.

Prolactin receptor in regulation of neuronal excitability and channels

PubMed Central

Patil, Mayur J; Henry, Michael A; Akopian, Armen N

2014-01-01

Prolactin (PRL) activates PRL receptor isoforms to exert regulation of specific neuronal circuitries, and to control numerous physiological and clinically-relevant functions including; maternal behavior, energy balance and food intake, stress and trauma responses, anxiety, neurogenesis, migraine and pain. PRL controls these critical functions by regulating receptor potential thresholds, neuronal excitability and/or neurotransmission efficiency. PRL also influences neuronal functions via activation of certain neurons, resulting in Ca2+ influx and/or electrical firing with subsequent release of neurotransmitters. Although PRL was identified almost a century ago, very little specific information is known about how PRL regulates neuronal functions. Nevertheless, important initial steps have recently been made including the identification of PRL-induced transient signaling pathways in neurons and the modulation of neuronal transient receptor potential (TRP) and Ca2+-dependent K+ channels by PRL. In this review, we summarize current knowledge and recent progress in understanding the regulation of neuronal excitability and channels by PRL. PMID:24758841

The Healthy Immigrant Paradox and Child Maltreatment: A Systematic Review.

PubMed

Millett, Lina S

2016-10-01

Prior studies suggest that foreign-born individuals have a health advantage, referred to as the Healthy Immigrant Paradox, when compared to native-born persons of the same socio-economic status. This systematic review examined whether the immigrant advantage found in health literature is mirrored by child maltreatment in general and its forms in particular. The author searched Academic Search Premier, CINAHL, CINAHL PLUS, Family and Society Studies Worldwide, MEDLINE, PsychINFO, Social Work Abstracts, and SocINdex for published literature through December 2015. The review followed an evidence-based Preferred Reporting Items for Systematic reviews and Meta-Analyses checklist. The author identified 822 unique articles, of which 19 met the inclusion criteria. The reviewed data showed strong support for the healthy immigrant paradox for a general form of maltreatment and physical abuse. The evidence for emotional and sexual abuse was also suggestive of immigrant advantage though relatively small sample size and lack of multivariate controls make these findings tentative. The evidence for neglect was mixed: immigrants were less likely to be reported to Child Protective Services; however, they had higher rates of physical neglect and lack of supervision in the community data. The study results warrant confirmation with newer data possessing strong external validity for immigrant samples.

Mysteries of TGF-β Paradox in Benign and Malignant Cells.

PubMed

Zhang, Qiang; Yu, Nengwang; Lee, Chung

2014-01-01

TGF-β regulates a wide range of biological functions including embryonic development, wound healing, organogenesis, immune modulation, and cancer progression. Interestingly, TGF-β is known to inhibit cell growth in benign cells but promote progression in cancer cells; this phenomenon is known as TGF-β paradox. To date, the mechanism of this paradox still remains a scientific mystery. In this review, we present our experience, along with the literature, in an attempt to answer this mystery. First, we observed that, on TGF-β engagement, there is a differential activation of Erk between benign and cancer cells. Since activated Erk is a major mediator in tumor progression and metastasis, a differentially activated Erk represents the answer to this mystery. Second, we identified a key player, PP2A-B56α, which is differentially recruited by the activated type I TGF-β receptor (TBRI) in benign and tumor cells, resulting in differential Erk activation. Finally, TGF-β stimulation leads to suppressed TBRs in tumor cells but not in benign cells. This differentially suppressed TBRs triggers differential recruitment of PP2A-B56α and, thus, differential activation of Erk. The above three events explain the mysteries of TGF-β paradox. Understanding the mechanism of TGF-β paradox will help us to predict indolent from aggressive cancers and develop novel anti-cancer strategies.

Mysteries of TGF-β Paradox in Benign and Malignant Cells

PubMed Central

Zhang, Qiang; Yu, Nengwang; Lee, Chung

2014-01-01

TGF-β regulates a wide range of biological functions including embryonic development, wound healing, organogenesis, immune modulation, and cancer progression. Interestingly, TGF-β is known to inhibit cell growth in benign cells but promote progression in cancer cells; this phenomenon is known as TGF-β paradox. To date, the mechanism of this paradox still remains a scientific mystery. In this review, we present our experience, along with the literature, in an attempt to answer this mystery. First, we observed that, on TGF-β engagement, there is a differential activation of Erk between benign and cancer cells. Since activated Erk is a major mediator in tumor progression and metastasis, a differentially activated Erk represents the answer to this mystery. Second, we identified a key player, PP2A-B56α, which is differentially recruited by the activated type I TGF-β receptor (TBRI) in benign and tumor cells, resulting in differential Erk activation. Finally, TGF-β stimulation leads to suppressed TBRs in tumor cells but not in benign cells. This differentially suppressed TBRs triggers differential recruitment of PP2A-B56α and, thus, differential activation of Erk. The above three events explain the mysteries of TGF-β paradox. Understanding the mechanism of TGF-β paradox will help us to predict indolent from aggressive cancers and develop novel anti-cancer strategies. PMID:24860782

Interpreting irregularity in small-scale, cyclical precipitation of halite-anhydrite couplets within the Pennsylvanian Paradox Formation, Paradox Basin, Utah

NASA Astrophysics Data System (ADS)

Marra, K. R.; Agena, W. F.; Dubiel, R. F.; Lee, M. W.; Pitman, J. K.

2012-12-01

The Pennsylvanian Paradox Formation (Hermosa Group) contains 33 documented evaporite cycles consisting of thick (6-240 m) halite successions interbedded with anhydrite, silty dolomite, and black shale. The evaporite deposits precipitated from marine brines under restricted circulation conditions in the Paradox Basin, a northwest-southeast trending asymmetrical trough formed adjacent to the Uncompahgre uplift, where periodic glacioeustatic sea-level fluctuations and intermittent meteoric water influxes altered salinity gradients. Each salt cycle contains rhythmically bedded halite-anhydrite couplets, in which anhedral to euhedral bottom-growth halite crystals are overlain by thin (mm-scale), subaqueously precipitated layers of anhydrite in the form of "snow-on-the-roof" texture. Discrete grains of sylvite, which are red due to hematite inclusions, locally occur as bands or aggregates throughout most salt packages. In order to delineate controls on high-frequency halite-anhydrite precipitation, the thickness of distinct couplets were measured in four salt cycles, two (Cycles 3 and 5) in the Cane Creek No.1 corehole and two (Cycles 5 and 13) in the Shafer No. 1 corehole. The cores were drilled approximately 8 km apart within the central portion of the basin near the crests of the Cane Creek and Shafer salt anticlines. The thickness of halite-anhydrite couplets ranges between 1-90 cm for all measured cycles, with the most commonly occurring thickness of approximately 3-4 cm. Despite the proximity of the two cores, the salt cycles in the Shafer No. 1 core are 12-15m thicker than in the Cane Creek No. 1 core, and individual couplets thicken within the middle (~20 m) of the salt section. In contrast, couplets thicken near the top of the halite bed in the Cane Creek No.1 core, which is most pronounced in Cycle 5. Locally disrupted and distorted laminae due to salt flowage, however, complicates some laminae measurements. The small-scale, cyclical pattern of halite

Crystallization Age of NWA 1460 Shergottite: Paradox Revisited

NASA Technical Reports Server (NTRS)

Nyquist, L. E.; Shih, C-Y.; Reese, Y. D.; Irving, A. J.

2004-01-01

We have determined the Rb-Sr age of basaltic shergottite NWA 1460 to be 312 +/- 3 Ma, and the Sm-Nd age to be 352 +/- 30 Ma. The initial Sr and Nd isotopic compositions of NWA 1460 suggest it is an earlier melting product of a Martian mantle source region similar to those of the Iherzolitic shergottites and basaltic shergottite EETA79001, lithology B. The new ages of NWA 1460 and other recently analyzed Martian meteorites leads us to reexamine the paradox that most of the Martian meteorites appear to be younger from the majority of the Martian surface. This paradox continues to pose a challenge to determining a reliable Martian chronology.

Controlling automatic imitative tendencies: interactions between mirror neuron and cognitive control systems.

PubMed

Cross, Katy A; Torrisi, Salvatore; Reynolds Losin, Elizabeth A; Iacoboni, Marco

2013-12-01

Humans have an automatic tendency to imitate others. Although several regions commonly observed in social tasks have been shown to be involved in imitation control, there is little work exploring how these regions interact with one another. We used fMRI and dynamic causal modeling to identify imitation-specific control mechanisms and examine functional interactions between regions. Participants performed a pre-specified action (lifting their index or middle finger) in response to videos depicting the same two actions (biological cues) or dots moving with similar trajectories (non-biological cues). On congruent trials, the stimulus and response were similar (e.g. index finger response to index finger or left side dot stimulus), while on incongruent trials the stimulus and response were dissimilar (e.g. index finger response to middle finger or right side dot stimulus). Reaction times were slower on incongruent compared to congruent trials for both biological and non-biological stimuli, replicating previous findings that suggest the automatic imitative or spatially compatible (congruent) response must be controlled on incongruent trials. Neural correlates of the congruency effects were different depending on the cue type. The medial prefrontal cortex, anterior cingulate, inferior frontal gyrus pars opercularis (IFGpo) and the left anterior insula were involved specifically in controlling imitation. In addition, the IFGpo was also more active for biological compared to non-biological stimuli, suggesting that the region represents the frontal node of the human mirror neuron system (MNS). Effective connectivity analysis exploring the interactions between these regions, suggests a role for the mPFC and ACC in imitative conflict detection and the anterior insula in conflict resolution processes, which may occur through interactions with the frontal node of the MNS. We suggest an extension of the previous models of imitation control involving interactions between imitation

The mesencephalic reticular formation as a conduit for primate collicular gaze control: tectal inputs to neurons targeting the spinal cord and medulla.

PubMed

Perkins, Eddie; Warren, Susan; May, Paul J

2009-08-01

The superior colliculus (SC), which directs orienting movements of both the eyes and head, is reciprocally connected to the mesencephalic reticular formation (MRF), suggesting the latter is involved in gaze control. The MRF has been provisionally subdivided to include a rostral portion, which subserves vertical gaze, and a caudal portion, which subserves horizontal gaze. Both regions contain cells projecting downstream that may provide a conduit for tectal signals targeting the gaze control centers which direct head movements. We determined the distribution of cells targeting the cervical spinal cord and rostral medullary reticular formation (MdRF), and investigated whether these MRF neurons receive input from the SC by the use of dual tracer techniques in Macaca fascicularis monkeys. Either biotinylated dextran amine or Phaseolus vulgaris leucoagglutinin was injected into the SC. Wheat germ agglutinin conjugated horseradish peroxidase was placed into the ipsilateral cervical spinal cord or medial MdRF to retrogradely label MRF neurons. A small number of medially located cells in the rostral and caudal MRF were labeled following spinal cord injections, and greater numbers were labeled in the same region following MdRF injections. In both cases, anterogradely labeled tectoreticular terminals were observed in close association with retrogradely labeled neurons. These close associations between tectoreticular terminals and neurons with descending projections suggest the presence of a trans-MRF pathway that provides a conduit for tectal control over head orienting movements. The medial location of these reticulospinal and reticuloreticular neurons suggests this MRF region may be specialized for head movement control. (c) 2009 Wiley-Liss, Inc.

A Wnt1 regulated Frizzled-1/β-Catenin signaling pathway as a candidate regulatory circuit controlling mesencephalic dopaminergic neuron-astrocyte crosstalk: Therapeutical relevance for neuron survival and neuroprotection

PubMed Central

2011-01-01

Background Dopamine-synthesizing (dopaminergic, DA) neurons in the ventral midbrain (VM) constitute a pivotal neuronal population controlling motor behaviors, cognitive and affective brain functions, which generation critically relies on the activation of Wingless-type MMTV integration site (Wnt)/β-catenin pathway in their progenitors. In Parkinson's disease, DA cell bodies within the substantia nigra pars compacta (SNpc) progressively degenerate, with causes and mechanisms poorly understood. Emerging evidence suggests that Wnt signaling via Frizzled (Fzd) receptors may play a role in different degenerative states, but little is known about Wnt signaling in the adult midbrain. Using in vitro and in vivo model systems of DA degeneration, along with functional studies in both intact and SN lesioned mice, we herein highlight an intrinsic Wnt1/Fzd-1/β-catenin tone critically contributing to the survival and protection of adult midbrain DA neurons. Results In vitro experiments identifie Fzd-1 receptor expression at a mRNA and protein levels in dopamine transporter (DAT) expressing neurons, and demonstrate the ability of exogenous Wnt1 to exert robust neuroprotective effects against Caspase-3 activation, the loss of tyrosine hydroxylase-positive (TH+) neurons and [3H] dopamine uptake induced by different DA-specific insults, including serum and growth factor deprivation, 6-hydroxydopamine and MPTP/MPP+. Co-culture of DA neurons with midbrain astrocytes phenocopies Wnt1 neuroprotective effects, whereas RNA interference-mediated knockdown of Wnt1 in midbrain astrocytes markedly reduces astrocyte-induced TH+ neuroprotection. Likewise, silencing β-catenin mRNA or knocking down Fzd-1 receptor expression in mesencephalic neurons counteract astrocyte-induced TH+ neuroprotection. In vivo experiments document Fzd-1 co-localization with TH+ neurons within the intact SNpc and blockade of Fzd/β-catenin signaling by unilateral infusion of a Fzd/β-catenin antagonist within the SN

The calcium paradox - What should we have to fear?

PubMed Central

de Oliveira, Marcos Aurélio Barboza; Brandi, Antônio Carlos; dos Santos, Carlos Alberto; Botelho, Paulo Henrique Husseni; Cortez, José Luís Lasso; Goissis, Gilberto; Braile, Domingo Marcolino

2014-01-01

The calcium paradox was first mentioned in 1966 by Zimmerman et al. Thereafter gained great interest from the scientific community due to the fact of the absence of calcium ions in heart muscle cells produce damage similar to ischemia-reperfusion. Although not all known mechanisms involved in cellular injury in the calcium paradox intercellular connection maintained only by nexus seems to have a key role in cellular fragmentation. The addition of small concentrations of calcium, calcium channel blockers, and hyponatraemia hypothermia are important to prevent any cellular damage during reperfusion solutions with physiological concentration of calcium. PMID:25140476

Remote Control of Neuronal Signaling

PubMed Central

Rogan, Sarah C.

2011-01-01

A significant challenge for neuroscientists is to determine how both electrical and chemical signals affect the activity of cells and circuits and how the nervous system subsequently translates that activity into behavior. Remote, bidirectional manipulation of those signals with high spatiotemporal precision is an ideal approach to addressing that challenge. Neuroscientists have recently developed a diverse set of tools that permit such experimental manipulation with varying degrees of spatial, temporal, and directional control. These tools use light, peptides, and small molecules to primarily activate ion channels and G protein-coupled receptors (GPCRs) that in turn activate or inhibit neuronal firing. By monitoring the electrophysiological, biochemical, and behavioral effects of such activation/inhibition, researchers can better understand the links between brain activity and behavior. Here, we review the tools that are available for this type of experimentation. We describe the development of the tools and highlight exciting in vivo data. We focus primarily on designer GPCRs (receptors activated solely by synthetic ligands, designer receptors exclusively activated by designer drugs) and microbial opsins (e.g., channelrhodopsin-2, halorhodopsin, Volvox carteri channelrhodopsin) but also describe other novel techniques that use orthogonal receptors, caged ligands, allosteric modulators, and other approaches. These tools differ in the direction of their effect (activation/inhibition, hyperpolarization/depolarization), their onset and offset kinetics (milliseconds/minutes/hours), the degree of spatial resolution they afford, and their invasiveness. Although none of these tools is perfect, each has advantages and disadvantages, which we describe, and they are all still works in progress. We conclude with suggestions for improving upon the existing tools. PMID:21415127

Neuropeptide secreted from a pacemaker activates neurons to control a rhythmic behavior.

PubMed

Wang, Han; Girskis, Kelly; Janssen, Tom; Chan, Jason P; Dasgupta, Krishnakali; Knowles, James A; Schoofs, Liliane; Sieburth, Derek

2013-05-06

Rhythmic behaviors are driven by endogenous biological clocks in pacemakers, which must reliably transmit timing information to target tissues that execute rhythmic outputs. During the defecation motor program in C. elegans, calcium oscillations in the pacemaker (intestine), which occur about every 50 s, trigger rhythmic enteric muscle contractions through downstream GABAergic neurons that innervate enteric muscles. However, the identity of the timing signal released by the pacemaker and the mechanism underlying the delivery of timing information to the GABAergic neurons are unknown. Here, we show that a neuropeptide-like protein (NLP-40) released by the pacemaker triggers a single rapid calcium transient in the GABAergic neurons during each defecation cycle. We find that mutants lacking nlp-40 have normal pacemaker function, but lack enteric muscle contractions. NLP-40 undergoes calcium-dependent release that is mediated by the calcium sensor, SNT-2/synaptotagmin. We identify AEX-2, the G-protein-coupled receptor on the GABAergic neurons, as the receptor for NLP-40. Functional calcium imaging reveals that NLP-40 and AEX-2/GPCR are both necessary for rhythmic activation of these neurons. Furthermore, acute application of synthetic NLP-40-derived peptide depolarizes the GABAergic neurons in vivo. Our results show that NLP-40 carries the timing information from the pacemaker via calcium-dependent release and delivers it to the GABAergic neurons by instructing their activation. Thus, we propose that rhythmic release of neuropeptides can deliver temporal information from pacemakers to downstream neurons to execute rhythmic behaviors. Copyright © 2013 Elsevier Ltd. All rights reserved.

Neuropeptide Secreted from a Pacemaker Activates Neurons to Control a Rhythmic Behavior

PubMed Central

Wang, Han; Girskis, Kelly; Janssen, Tom; Chan, Jason P.; Dasgupta, Krishnakali; Knowles, James A.; Schoofs, Liliane; Sieburth, Derek

2013-01-01

Summary Background Rhythmic behaviors are driven by endogenous biological clocks in pacemakers, which must reliably transmit timing information to target tissues that execute rhythmic outputs. During the defecation motor program in C. elegans, calcium oscillations in the pacemaker (intestine), which occur about every 50 seconds, trigger rhythmic enteric muscle contractions through downstream GABAergic neurons that innervate enteric muscles. However, the identity of the timing signal released by the pacemaker and the mechanism underlying the delivery of timing information to the GABAergic neurons are unknown. Results Here we show that a neuropeptide-like protein (NLP-40) released by the pacemaker triggers a single rapid calcium transient in the GABAergic neurons during each defecation cycle. We find that mutants lacking nlp-40 have normal pacemaker function, but lack enteric muscle contractions. NLP-40 undergoes calcium-dependent release that is mediated by the calcium sensor, SNT-2/synaptotagmin. We identify AEX-2, the G protein-coupled receptor on the GABAergic neurons, as the receptor of NLP-40. Functional calcium imaging reveals that NLP-40 and AEX-2/GPCR are both necessary for rhythmic activation of these neurons. Furthermore, acute application of synthetic NLP-40-derived peptide depolarizes the GABAergic neurons in vivo. Conclusions Our results show that NLP-40 carries the timing information from the pacemaker via calcium-dependent release and delivers it to the GABAergic neurons by instructing their activation. Thus, we propose that rhythmic release of neuropeptides can deliver temporal information from pacemakers to downstream neurons to execute rhythmic behaviors. PMID:23583549

Quantum structure in economics: The Ellsberg paradox

NASA Astrophysics Data System (ADS)

Aerts, Diederik; Sozzo, Sandro

2012-03-01

The expected utility hypothesis and Savage's Sure-Thing Principle are violated in real life decisions, as shown by the Allais and Ellsberg paradoxes. The popular explanation in terms of ambiguity aversion is not completely accepted. As a consequence, uncertainty is still problematical in economics. To overcome these difficulties a distinction between risk and ambiguity has been introduced which depends on the existence of a Kolmogorovian probabilistic structure modeling these uncertainties. On the other hand, evidence of everyday life suggests that context plays a fundamental role in human decisions under uncertainty. Moreover, it is well known from physics that any probabilistic structure modeling contextual interactions between entities structurally needs a non-Kolmogorovian framework admitting a quantum-like representation. For this reason, we have recently introduced a notion of contextual risk to mathematically capture situations in which ambiguity occurs. We prove in this paper that the contextual risk approach can be applied to the Ellsberg paradox, and elaborate a sphere model within our hidden measurement formalism which reveals that it is the overall conceptual landscape that is responsible of the disagreement between actual human decisions and the predictions of expected utility theory, which generates the paradox. This result points to the presence of a quantum conceptual layer in human thought which is superposed to the usually assumed classical logical layer, and conceptually supports the thesis of several authors suggesting the presence of quantum structure in economics and decision theory.

Nomadic-colonial life strategies enable paradoxical survival and growth despite habitat destruction

PubMed Central

Tan, Zong Xuan; Cheong, Kang Hao

2017-01-01

Organisms often exhibit behavioral or phenotypic diversity to improve population fitness in the face of environmental variability. When each behavior or phenotype is individually maladaptive, alternating between these losing strategies can counter-intuitively result in population persistence–an outcome similar to the Parrondo’s paradox. Instead of the capital or history dependence that characterize traditional Parrondo games, most ecological models which exhibit such paradoxical behavior depend on the presence of exogenous environmental variation. Here we present a population model that exhibits Parrondo’s paradox through capital and history-dependent dynamics. Two sub-populations comprise our model: nomads, who live independently without competition or cooperation, and colonists, who engage in competition, cooperation, and long-term habitat destruction. Nomads and colonists may alternate behaviors in response to changes in the colonial habitat. Even when nomadism and colonialism individually lead to extinction, switching between these strategies at the appropriate moments can paradoxically enable both population persistence and long-term growth. DOI: http://dx.doi.org/10.7554/eLife.21673.001 PMID:28084993

Paradoxical skin lesions induced by anti-TNF-α agents in SAPHO syndrome.

PubMed

Li, Chen; Wu, Xia; Cao, Yihan; Zeng, Yueping; Zhang, Weihong; Zhang, Shuo; Liu, Yuehua; Jin, Hongzhong; Zhang, Wen; Li, Li

2018-04-03

The objectives of the study were to characterize the clinical picture of paradoxical skin lesions in SAPHO patients treated with anti-TNF-α agents and to explore its pathogenesis. Patients treated with anti-TNF-α therapy were identified from a cohort of 164 SAPHO patients. The clinical data and skin biopsies were collected. The usage, efficacy, and side effects of anti-TNF-α therapy were recorded. Forty-one (25.0%) patients received anti-TNF-α therapy, of which seven (17.1%) developed paradoxical skin lesions after 1 to 14 infusions. Patients with such lesions were older at onset of skin lesions than those without (p = 0.034). Expression of TNF-α in palmoplantar pustulosis increased after anti-TNF-α therapy in the two examined patients with exacerbated skin lesions. Anti-TNF-α therapy induces paradoxical skin lesions in 17.1% SAPHO patients. Late onset of skin manifestations is associated with an increased risk of such lesions. The paradoxical elevation of TNF-α expression in lesions may contribute to this phenomenon.

The Faint Young Sun Paradox

NASA Astrophysics Data System (ADS)

Khramova, E. G.

2017-05-01

According to astrophysical models, the luminosity of the young Sun had to be by 30% lower than it is today, while according to paleoclimatic data, the Earth surface temperature in Archaea even somewhat exceeded the present-day values. The article analyzes some existing explanations of this discordance, draws attention to a number of unaccounted factors, and suggests a new hypothesis for solving the paradox.