bluuebunny/crossref_metadata_2025_split huggingface dataset:
Internal jugular pressure increases during parabolic flight
Authors: Martin David S. , Lee Stuart M. C. , Matz Timothy P. , Westby Christian M. , Scott Jessica M. , Stenger Michael B. , Platts Steven H. 
Published: December 2016

AbstractOne hypothesized contributor to vision changes experienced by >75% of International Space Station astronauts is elevated intracranial pressure (ICP). While no definitive data yet exist, elevated ICP might be secondary to the microgravity‐induced cephalad fluid shift, resulting in venous congestion (overfilling and distension) and inhibition of cerebrospinal and lymphatic fluid drainage from the skull. The objective of this study was to measure internal jugular venous pressure (IJVP) during normo‐ and hypo‐gravity as an index of venous congestion. IJVP was measured noninvasively using compression sonography at rest during end‐expiration in 11 normal, healthy subjects (3 M, 8 F) during normal gravity (1G; supine) and weightlessness (0G; seated) produced by parabolic flight. IJVP also was measured in two subjects during parabolas approximating Lunar (1/6G) and Martian gravity (1/3G). Finally, IJVP was measured during increased intrathoracic pressure produced using controlled Valsalva maneuvers. IJVP was higher in 0G than 1G (23.9 ± 5.6 vs. 9.9 ± 5.1 mmHg, mean ± SD P < 0.001) in all subjects, and IJVP increased as gravity levels decreased in two subjects. Finally, IJVP was greater in 0G than 1G at all expiration pressures (P < 0.01). Taken together, these data suggest that IJVP is elevated during acute exposure to reduced gravity and may be elevated further by conditions that increase intrathoracic pressure, a strong modulator of central venous pressure and IJVP. However, whether elevated IJVP, and perhaps consequent venous congestion, observed during acute microgravity exposure contribute to vision changes during long‐duration spaceflight is yet to be determined.
Effects of novel muscarinic M3 receptor ligand C1213 in pulmonary arterial hypertension models
Authors: Ahmed Mohamed , VanPatten Sonya , Lakshminrusimha Satyan , Patel Hardik , Coleman Thomas R. , Al‐Abed Yousef 
Published: December 2016

AbstractPulmonary hypertension (PH) is a complex disease comprising a pathologic remodeling and thickening of the pulmonary vessels causing an after load on the right heart ventricle that can result in ventricular failure. Triggered by oxidative stress, episodes of hypoxia, and other undetermined causes, PH is associated with poor outcomes and a high rate of morbidity. In the neonate, this disease has a similar etiology but is further complicated by the transition to breathing after birth, which requires a reduction in vascular resistance. Persistent pulmonary hypertension of the newborn (PPHN) is one form of PH that is frequently unresponsive to current therapies including inhaled nitric oxide (due to lack of proper absorption and diffusion), and other therapeutics targeting signaling mediators in vascular endothelium and smooth muscle. The need for novel agents, which target distinct pathways in pulmonary hypertension, remains. Herein, we investigated the therapeutic effects of novel muscarinic receptor ligand C1213 in models of PH. We demonstrated that via M3 muscarinic receptors, C1213 induced activating‐ eNOS phosphorylation (serine‐1177), which is known to lead to nitric oxide (NO) production in endothelial cells. Using signaling pathway inhibitors, we discovered that AKT and calcium signaling contributed to eNOS phosphorylation induced by C1213. As expected for an eNOS‐stimulating agent, in ex vivo and in vivo models, C1213 triggered pulmonary vasodilation and induced both pulmonary artery and systemic blood pressure reductions demonstrating its potential value in PH and PPHN. In brief, this proof‐of‐concept study provides evidence that an M3 muscarinic receptor functionally selective ligand stimulates downstream pathways leading to antihypertensive effects using in vitro, ex vivo, and in vivo models of PH.
Nasal TRPA1 mediates irritant‐induced bradypnea in mice
Authors: Inui Keiichi , Chen ChangPing , Pauli Jordan L. , Kuroki Chiharu , Tashiro Shogo , Kanmura Yuichi , Kashiwadani Hideki , Kuwaki Tomoyuki 
Published: December 2016

AbstractTransient receptor potential ankyrin 1 (TRPA1), a member of the TRP superfamily, exists in sensory neurons such as trigeminal neurons innervating the nasal cavity and vagal neurons innervating the trachea and the lung. Although TRPA1 has been proposed as an irritant receptor that, when stimulated, triggers bradypnea, precise locations of the receptors responsible have not been elucidated. Here, we examined the relative importance of TRPA1 located in the upper airway (nasal) and the lower airway (trachea/lungs) in urethane‐anesthetized mice. To stimulate the upper and lower airways separately, two cannulas were inserted through a hole made in the trachea just caudal to the thyroid cartilage, one into the nasal cavity and the second into the lower trachea. A vapor of one of the TRPA1‐agonists, allyl isothiocyanate (AITC), was introduced by placing a piece of cotton paper soaked with AITC solution into the airline. AITC decreased the respiratory frequency when applied to the upper airway (ca −30%) but not to the lower airway (ca −5%). No response was observed in TRPA1 knockout mice. Contribution of the olfactory nerve seemed minimal because olfactory bulbectomized wild‐type mice showed a similar response to that of the intact mice. AITC‐induced bradypnea seemed to be mediated, at least in part, by the trigeminal nerve because trigeminal ganglion neurons were activated by AITC as revealed by an increase in the phosphorylated form of extracellular signal‐regulated kinase in the neurons. These data clearly show that trigeminal TRPA1 in the nasal cavity play an essential role in irritant‐induced bradypnea.
A Model of the Superior Colliculus Predicts Fixation Locations during Scene Viewing and Visual Search
Authors: Adeli Hossein , Vitu Françoise , Zelinsky Gregory J. 
Published: December 2016

Modern computational models of attention predict fixations using saliency maps and target maps, which prioritize locations for fixation based on feature contrast and target goals, respectively. But whereas many such models are biologically plausible, none have looked to the oculomotor system for design constraints or parameter specification. Conversely, although most models of saccade programming are tightly coupled to underlying neurophysiology, none have been tested using real-world stimuli and tasks. We combined the strengths of these two approaches in MASC, a model of attention in the superior colliculus (SC) that captures known neurophysiological constraints on saccade programming. We show that MASC predicted the fixation locations of humans freely viewing naturalistic scenes and performing exemplar and categorical search tasks, a breadth achieved by no other existing model. Moreover, it did this as well or better than its more specialized state-of-the-art competitors. MASC's predictive success stems from its inclusion of high-level but core principles of SC organization: an over-representation of foveal information, size-invariant population codes, cascaded population averaging over distorted visual and motor maps, and competition between motor point images for saccade programming, all of which cause further modulation of priority (attention) after projection of saliency and target maps to the SC. Only by incorporating these organizing brain principles into our models can we fully understand the transformation of complex visual information into the saccade programs underlying movements of overt attention. With MASC, a theoretical footing now exists to generate and test computationally explicit predictions of behavioral and neural responses in visually complex real-world contexts.SIGNIFICANCE STATEMENTThe superior colliculus (SC) performs a visual-to-motor transformation vital to overt attention, but existing SC models cannot predict saccades to visually complex real-world stimuli. We introduce a brain-inspired SC model that outperforms state-of-the-art image-based competitors in predicting the sequences of fixations made by humans performing a range of everyday tasks (scene viewing and exemplar and categorical search), making clear the value of looking to the brain for model design. This work is significant in that it will drive new research by making computationally explicit predictions of SC neural population activity in response to naturalistic stimuli and tasks. It will also serve as a blueprint for the construction of other brain-inspired models, helping to usher in the next generation of truly intelligent autonomous systems.
Cholinergic, Glutamatergic, and GABAergic Neurons of the Pedunculopontine Tegmental Nucleus Have Distinct Effects on Sleep/Wake Behavior in Mice
Authors: Kroeger Daniel , Ferrari Loris L. , Petit Gaetan , Mahoney Carrie E. , Fuller Patrick M. , Arrigoni Elda , Scammell Thomas E. 
Published: December 2016

The pedunculopontine tegmental (PPT) nucleus has long been implicated in the regulation of cortical activity and behavioral states, including rapid eye-movement (REM) sleep. For example, electrical stimulation of the PPT region during sleep leads to rapid awakening, whereas lesions of the PPT in cats reduce REM sleep. Though these effects have been linked with the activity of cholinergic PPT neurons, the PPT also includes intermingled glutamatergic and GABAergic cell populations, and the precise roles of cholinergic, glutamatergic, and GABAergic PPT cell groups in regulating cortical activity and behavioral state remain unknown. Using a chemogenetic approach in three Cre-driver mouse lines, we found that selective activation of glutamatergic PPT neurons induced prolonged cortical activation and behavioral wakefulness, whereas inhibition reduced wakefulness and increased non-REM (NREM) sleep. Activation of cholinergic PPT neurons suppressed lower-frequency electroencephalogram rhythms during NREM sleep. Last, activation of GABAergic PPT neurons slightly reduced REM sleep. These findings reveal that glutamatergic, cholinergic, and GABAergic PPT neurons differentially influence cortical activity and sleep/wake states.SIGNIFICANCE STATEMENTMore than 40 million Americans suffer from chronic sleep disruption, and the development of effective treatments requires a more detailed understanding of the neuronal mechanisms controlling sleep and arousal. The pedunculopontine tegmental (PPT) nucleus has long been considered a key site for regulating wakefulness and REM sleep. This is mainly because of the cholinergic neurons contained in the PPT nucleus. However, the PPT nucleus also contains glutamatergic and GABAergic neurons that likely contribute to the regulation of cortical activity and sleep–wake states. The chemogenetic experiments in the present study reveal that cholinergic, glutamatergic, and GABAergic PPT neurons each have distinct effects on sleep/wake behavior, improving our understanding of how the PPT nucleus regulates cortical activity and behavioral states.
Granular Layer Neurons Control Cerebellar Neurovascular Coupling Through an NMDA Receptor/NO-Dependent System
Authors: Mapelli Lisa , Gagliano Giuseppe , Soda Teresa , Laforenza Umberto , Moccia Francesco , D'Angelo Egidio U. 
Published: December 2016

Neurovascular coupling (NVC) is the process whereby neuronal activity controls blood vessel diameter. In the cerebellum, the molecular layer is regarded as the main NVC determinant. However, the granular layer is a region with variable metabolic demand caused by large activity fluctuations that shows a prominent expression of NMDA receptors (NMDARs) and nitric oxide synthase (NOS) and is therefore much more suitable for effective NVC. Here, we show, in the granular layer of acute rat cerebellar slices, that capillary diameter changes rapidly after mossy fiber stimulation. Vasodilation required neuronal NMDARs and NOS stimulation and subsequent guanylyl cyclase activation that probably occurred in pericytes. Vasoconstriction required metabotropic glutamate receptors and CYP ω-hydroxylase, the enzyme regulating 20-hydroxyeicosatetraenoic acid production. Therefore, granular layer capillaries are controlled by the balance between vasodilating and vasoconstricting systems that could finely tune local blood flow depending on neuronal activity changes at the cerebellar input stage.SIGNIFICANCE STATEMENTThe neuronal circuitry and the biochemical pathways that control local blood flow supply in the cerebellum are unclear. This is surprising given the emerging role played by this brain structure, not only in motor behavior, but also in cognitive functions. Although previous studies focused on the molecular layer, here, we shift attention onto the mossy fiber granule cell (GrC) relay. We demonstrate that GrC activity causes a robust vasodilation in nearby capillaries via the NMDA receptors–neuronal nitric oxide synthase signaling pathway. At the same time, metabotropic glutamate receptors mediate 20-hydroxyeicosatetraenoic acid-dependent vasoconstriction. These results reveal a complex signaling network that hints for the first time at the granular layer as a major determinant of cerebellar blood-oxygen-level-dependent signals.
Removal of Perineuronal Nets Unlocks Juvenile Plasticity Through Network Mechanisms of Decreased Inhibition and Increased Gamma Activity
Authors: Lensjø Kristian Kinden , Lepperød Mikkel Elle , Dick Gunnar , Hafting Torkel , Fyhn Marianne 
Published: December 2016

Perineuronal nets (PNNs) are extracellular matrix structures mainly enwrapping parvalbumin-expressing inhibitory neurons. The assembly of PNNs coincides with the end of the period of heightened visual cortex plasticity in juveniles, whereas removal of PNNs in adults reopens for plasticity. The mechanisms underlying this phenomenon remain elusive. We have used chronic electrophysiological recordings to investigate accompanying electrophysiological changes to activity-dependent plasticity and we report on novel mechanisms involved in both induced and critical period plasticity. By inducing activity-dependent plasticity in the visual cortex of adult rats while recording single unit and population activity, we demonstrate that PNN removal alters the balance between inhibitory and excitatory spiking activity directly. Without PNNs, inhibitory activity was reduced, whereas spiking variability was increased as predicted in a simulation with a Brunel neural network. Together with a shift in ocular dominance and large effects on unit activity during the first 48 h of monocular deprivation (MD), we show that PNN removal resets the neural network to an immature, juvenile state. Furthermore, in PNN-depleted adults as well as in juveniles, MD caused an immediate potentiation of gamma activity, suggesting a novel mechanism initiating activity-dependent plasticity and driving the rapid changes in unit activity.SIGNIFICANCE STATEMENTEmerging evidence suggests a role for perineuronal nets (PNNs) in learning and regulation of plasticity, but the underlying mechanisms remain unresolved. Here, we used chronicin vivoextracellular recordings to investigate how removal of PNNs opens for plasticity and how activity-dependent plasticity affects neural activity over time. PNN removal caused reduced inhibitory activity and reset the network to a juvenile state. Experimentally induced activity-dependent plasticity by monocular deprivation caused rapid changes in single unit activity and a remarkable potentiation of gamma oscillations. Our results demonstrate how PNNs may be involved directly in stabilizing the neural network. Moreover, the immediate potentiation of gamma activity after plasticity onset points to potential new mechanisms for the initiation of activity-dependent plasticity.
A Mammalian Retinal Ganglion Cell Implements a Neuronal Computation That Maximizes the SNR of Its Postsynaptic Currents
Authors: Homann Jan , Freed Michael A. 
Published: December 2016

Neurons perform computations by integrating excitatory and inhibitory synaptic inputs. Yet, it is rarely understood what computation is being performed, or how much excitation or inhibition this computation requires. Here we present evidence for a neuronal computation that maximizes the signal-to-noise power ratio (SNR). We recorded from OFF delta retinal ganglion cells in the guinea pig retina and monitored synaptic currents that were evoked by visual stimulation (flashing dark spots). These synaptic currents were mediated by a decrease in an outward current from inhibitory synapses (disinhibition) combined with an increase in an inward current from excitatory synapses. We found that the SNR of combined excitatory and disinhibitory currents was voltage sensitive, peaking at membrane potentials near resting potential. At the membrane potential for maximal SNR, the amplitude of each current, either excitatory or disinhibitory, was proportional to its SNR. Such proportionate scaling is the theoretically best strategy for combining excitatory and disinhibitory currents to maximize the SNR of their combined current. Moreover, as spot size or contrast changed, the amplitudes of excitatory and disinhibitory currents also changed but remained in proportion to their SNRs, indicating a dynamic rebalancing of excitatory and inhibitory currents to maximize SNR.SIGNIFICANCE STATEMENTWe present evidence that the balance of excitatory and disinhibitory inputs to a type of retinal ganglion cell maximizes the signal-to-noise ratio power ratio (SNR) of its postsynaptic currents. This is significant because chemical synapses on a retinal ganglion cell require the probabilistic release of transmitter. Consequently, when the same visual stimulus is presented repeatedly, postsynaptic currents vary in amplitude. Thus, maximizing SNR may be a strategy for producing the most reliable signal possible given the inherent unreliability of synaptic transmission.
Hippocampal α-Synuclein in Dementia with Lewy Bodies Contributes to Memory Impairment and Is Consistent with Spread of Pathology
Authors: Adamowicz David H. , Roy Subhojit , Salmon David P. , Galasko Douglas R. , Hansen Lawrence A. , Masliah Eliezer , Gage Fred H. 
Published: December 2016

Despite considerable research to uncover them, the anatomic and neuropathologic correlates of memory impairment in dementia with Lewy bodies (DLB) remain unclear. While some studies have implicated Lewy bodies in the neocortex, others have pointed to α-synuclein pathology in the hippocampus. We systematically examined hippocampal Lewy pathology and its distribution in hippocampal subfields in 95 clinically and neuropathologically characterized human cases of DLB, finding that α-synuclein pathology was highest in two hippocampal-related subregions: the CA2 subfield and the entorhinal cortex (EC). While the EC had numerous classic somatic Lewy bodies, CA2 contained mainly Lewy neurites in presumed axon terminals, suggesting the involvement of the EC → CA2 circuitry in the pathogenesis of DLB symptoms. Clinicopathological correlations with measures of verbal and visual memory supported a role for EC Lewy pathology, but not CA2, in causing these memory deficits. Lewy pathology in CA1—the main output region for CA2—correlated best with results from memory testing despite a milder pathology. This result indicates that CA1 may be more functionally relevant than CA2 in the context of memory impairment in DLB. These correlations remained significant after controlling for several factors, including concurrent Alzheimer's pathology (neuritic plaques and neurofibrillary tangles) and the interval between time of testing and time of death. Our data suggest that although hippocampal Lewy pathology in DLB is predominant in CA2 and EC, memory performance correlates most strongly with CA1 burden.SIGNIFICANCE STATEMENTThis study provides a detailed neuropathologic analysis of hippocampal Lewy pathology in human patients with autopsy-confirmed dementia with Lewy bodies. The approach—informed by regional molecular markers, concurrent Alzheimer's pathology analysis, and relevant clinical data—helps tease out the relative contribution of Lewy pathology to memory dysfunction in the disease. Levels of Lewy pathology were found to be highest in the hippocampal CA2 subregion and entorhinal cortex, implicating a potentially overlooked circuit in disease pathogenesis. However, correlation with memory performance was strongest with CA1. This unexpected finding suggests that Lewy pathology must reach a critical burden across hippocampal circuitry to contribute to memory dysfunction beyond that related to other factors, notably coexisting Alzheimer's disease tau pathology.
Interação pai-criança e problemas externalizantes na infância
Authors: Araújo Freitas Luna Maiana , Alvarenga Patrícia 
Published: January 2017

O presente estudo avaliou a relação entre as habilidades sociais e práticas educativas negativas paternas e os problemas externalizantes na infância. Participaram do estudo 33 pais de crianças entre seis e nove anos. Os pais responderam ao Roteiro de Entrevista das Habilidades Sociais Educativas Parentais (RE-HSE-P) e ao Inventário de Comportamentos da Infância e Adolescência 6-18 anos (CBCL). Os resultados revelaram correlações positivas entre as práticas negativas paternas e os problemas externalizantes. Discutem-se as implicações das práticas negativas para o desenvolvimento de problemas externalizantes. Destaca-se a importância de considerar o papel mediador da interação mãe-filho sobre as relações entre as práticas paternas e estes problemas.
A Lei dos Agrotóxicos: um estudo sobre a responsabilidade referida aos produtores rurais do interior do Estado de São Paulo
Authors: Marques Maurício Dias , Braga Junior Sérgio Silva , Silva Dirceu da 
Published: December 2016

O presente artigo procurou verificar como os produtores rurais do município de Tupã-SP estão cumprindo a responsabilidade prevista na legislação, quanto à logística reversa das embalagens vazias de agrotóxicos. Com base em pesquisa documental, para compreender a determinação da legislação, e em pesquisa bibliográfica sobre a logística reversa, foi realizada uma pesquisa de campo com aplicação de um questionário desenvolvido e validado seguindo as recomendações de DeVellis (2003) junto a 20 (vinte) produtores rurais do município, nos meses de abril e maio de 2015. O objetivo foi verificar como os produtores rurais percebem o procedimento da logística reversa das embalagens de agrotóxicos, proposta pela legislação brasileira para essas embalagens. Verificou-se que existe certa tendência dos produtores, em geral, de não cumprir o que é imposto pela legislação e uma das possíveis causas levantadas nesta pesquisa pode ser a falta de fiscalização do Poder Público. PALAVRAS-CHAVE: Embalagens de agrotóxicos. Logística reversa. Legislação.