bluuebunny/crossref_metadata_2025 huggingface dataset:
Conversion of Synthetic Aβ toIn VivoActive Seeds and Amyloid Plaque Formation in a Hippocampal Slice Culture Model
Authors: Novotny Renata , Langer Franziska , Mahler Jasmin , Skodras Angelos , Vlachos Andreas , Wegenast-Braun Bettina M. , Kaeser Stephan A. , Neher Jonas J. , Eisele Yvonne S. , Pietrowski Marie J. , Nilsson K. Peter R. , Deller Thomas , Staufenbiel Matthias , Heimrich Bernd , Jucker Mathias
Published: May 2016

The aggregation of amyloid-β peptide (Aβ) in brain is an early event and hallmark of Alzheimer's disease (AD). We combined the advantages ofin vitroandin vivoapproaches to study cerebral β-amyloidosis by establishing a long-term hippocampal slice culture (HSC) model. While no Aβ deposition was noted in untreated HSCs of postnatal Aβ precursor protein transgenic (APP tg) mice, Aβ deposition emerged in HSCs when cultures were treated once with brain extract from aged APP tg mice and the culture medium was continuously supplemented with synthetic Aβ. Seeded Aβ deposition was also observed under the same conditions in HSCs derived from wild-type orApp-null mice but in no comparable way when HSCs were fixed before cultivation. Both the nature of the brain extract and the synthetic Aβ species determined the conformational characteristics of HSC Aβ deposition. HSC Aβ deposits induced a microglia response, spine loss, and neuritic dystrophy but no obvious neuron loss. Remarkably, in contrast toin vitroaggregated synthetic Aβ, homogenates of Aβ deposits containing HSCs induced cerebral β-amyloidosis upon intracerebral inoculation into young APP tg mice. Our results demonstrate that a living cellular environment promotes the seeded conversion of synthetic Aβ into a potentin vivoseeding-active form.

SIGNIFICANCE STATEMENTIn this study, we report the seeded induction of Aβ aggregation and deposition in long-term hippocampal slice cultures. Remarkably, we find that the biological activities of the largely synthetic Aβ aggregates in the culture are very similar to those observedin vivo. This observation is the first to show that potentin vivoseeding-active Aβ aggregates can be obtained by seeded conversion of synthetic Aβ in a living (wild-type) cellular environment.
Different Brain Circuitries Mediating Controllable and Uncontrollable Pain
Authors: Bräscher Anne-Kathrin , Becker Susanne , Hoeppli Marie-Eve , Schweinhardt Petra
Published: May 2016

Uncontrollable, compared with controllable, painful stimulation can lead to increased pain perception and activation in pain-processing brain regions, but it is currently unknown which brain areas mediate this effect. When pain is controllable, the lateral prefrontal cortex (PFC) seems to inhibit pain processing, although it is unclear how this is achieved. Using fMRI in healthy volunteers, we examined brain activation during controllable and uncontrollable stimulation to answer these questions. In the controllable task, participants self-adjusted temperatures applied to their hand of pain or warm intensities to provoke a constant sensation. In the uncontrollable task, the temperature time courses of the controllable task were replayed (yoked control) and participants rated their sensation continuously. During controllable pain trials, participants significantly downregulated the temperature to keep their sensation constant. Despite receiving the identical nociceptive input, intensity ratings increased during the uncontrollable pain trials. This additional sensitization was mirrored in increased activation of pain-processing regions such as insula, anterior cingulate cortex, and thalamus. Further, increased connectivity between the anterior insula and medial PFC (mPFC) in the uncontrollable and increased negative connectivity between dorsolateral PFC (dlPFC) and insula in the controllable task were observed. This suggests a pain-facilitating role of the mPFC during uncontrollable pain and a pain-inhibiting role of the dlPFC during controllable pain, both exerting their respective effects via the anterior insula. These results elucidate neural mechanisms of context-dependent pain modulation and their relation to subjective perception.

SIGNIFICANCE STATEMENTPain control is of uttermost importance and stimulus controllability is an important way to achieve endogenous pain modulation. Here, we show differential effects of controllability and uncontrollability on pain perception and cerebral pain processing. When pain was controllable, the dorsolateral prefrontal cortex downregulated pain-evoked activation in important pain-processing regions. In contrast, sensitization during uncontrollable pain was mediated by increased connectivity of the medial prefrontal cortex with the anterior insula and other pain-processing regions. These novel insights into cerebral pain modulation by stimulus controllability have the potential to improve treatment approaches in pain patients.
Striatopallidal Neuron NMDA Receptors Control Synaptic Connectivity, Locomotor, and Goal-Directed Behaviors
Authors: Lambot Laurie , Chaves Rodriguez Elena , Houtteman Delphine , Li Yuquing , Schiffmann Serge N. , Gall David , de Kerchove d'Exaerde Alban
Published: May 2016

The basal ganglia (BG) control action selection, motor programs, habits, and goal-directed learning. The striatum, the principal input structure of BG, is predominantly composed of medium-sized spiny neurons (MSNs). Arising from these spatially intermixed MSNs, two inhibitory outputs form two main efferent pathways, the direct and indirect pathways. Striatonigral MSNs give rise to the activating, direct pathway MSNs and striatopallidal MSNs to the inhibitory, indirect pathway (iMSNs). BG output nuclei integrate information from both pathways to fine-tune motor procedures and to acquire complex habits and skills. Therefore, balanced activity between both pathways is crucial for harmonious functions of the BG. Despite the increase in knowledge concerning the role of glutamate NMDA receptors (NMDA-Rs) in the striatum, understanding of the specific functions of NMDA-R iMSNs is still lacking. For this purpose, we generated a conditional knock-out mouse to address the functions of the NMDA-R in the indirect pathway. At the cellular level, deletion of GluN1 in iMSNs leads to a reduction in the number and strength of the excitatory corticostriatopallidal synapses. The subsequent scaling down in input integration leads to dysfunctional changes in BG output, which is seen as reduced habituation, delay in goal-directed learning, lack of associative behavior, and impairment in action selection or skill learning. The NMDA-R deletion in iMSNs causes a decrease in the synaptic strength of striatopallidal neurons, which in turn might lead to a imbalanced integration between direct and indirect MSN pathways, making mice less sensitive to environmental change. Therefore, their ability to learn and adapt to the environment-based experience was significantly affected.

SIGNIFICANCE STATEMENTThe striatum controls habits, locomotion, and goal-directed behaviors by coordinated activation of two antagonistic pathways. Insofar as NMDA receptors (NMDA-Rs) play a key role in synaptic plasticity essential for sustaining these behaviors, we generated a mouse model lacking NMDA-Rs specifically in striatopallidal neurons. To our knowledge, this is the first time that a specific deletion of inhibitory, indirect pathway medium-sized spiny neuron (iMSN) NMDA-Rs has been used to address the role of these receptors in the inhibitory pathway. Importantly, we found that this specific deletion led to a significant reduction in the number and strength of the cortico–iMSN synapses, which resulted in the significant impairments of behaviors orchestrated by the basal ganglia. Our findings indicate that the NMDA-Rs of the indirect pathway are essential for habituation, action selection, and goal-directed learning.
Optogenetic Stimulation of Prefrontal Glutamatergic Neurons Enhances Recognition Memory
Authors: Benn Abigail , Barker Gareth R. I. , Stuart Sarah A. , Roloff Eva v. L. , Teschemacher Anja G. , Warburton E. Clea , Robinson Emma S. J.
Published: May 2016

Finding effective cognitive enhancers is a major health challenge; however, modulating glutamatergic neurotransmission has the potential to enhance performance in recognition memory tasks. Previous studies using glutamate receptor antagonists have revealed that the medial prefrontal cortex (mPFC) plays a central role in associative recognition memory. The present study investigates short-term recognition memory using optogenetics to target glutamatergic neurons within the rodent mPFC specifically. Selective stimulation of glutamatergic neurons during the online maintenance of information enhanced associative recognition memory in normal animals. This cognitive enhancing effect was replicated by local infusions of the AMPAkine CX516, but not CX546, which differ in their effects on EPSPs. This suggests that enhancing the amplitude, but not the duration, of excitatory synaptic currents improves memory performance. Increasing glutamate release through infusions of the mGluR7 presynaptic receptor antagonist MMPIP had no effect on performance.

SIGNIFICANCE STATEMENTThese results provide new mechanistic information that could guide the targeting of future cognitive enhancers. Our work suggests that improved associative-recognition memory can be achieved by enhancing endogenous glutamatergic neuronal activity selectively using an optogenetic approach. We build on these observations to recapitulate this effect using drug treatments that enhance the amplitude of EPSPs; however, drugs that alter the duration of the EPSP or increase glutamate release lack efficacy. This suggests that both neural and temporal specificity are needed to achieve cognitive enhancement.
The Complement System Component C5a Produces Thermal Hyperalgesia via Macrophage-to-Nociceptor Signaling That Requires NGF and TRPV1
Authors: Shutov Leonid P. , Warwick Charles A. , Shi Xiaoyu , Gnanasekaran Aswini , Shepherd Andrew J. , Mohapatra Durga P. , Woodruff Trent M. , Clark J. David , Usachev Yuriy M.
Published: May 2016

The complement cascade is a principal component of innate immunity. Recent studies have underscored the importance of C5a and other components of the complement system in inflammatory and neuropathic pain, although the underlying mechanisms are largely unknown. In particular, it is unclear how the complement system communicates with nociceptors and which ion channels and receptors are involved. Here we demonstrate that inflammatory thermal and mechanical hyperalgesia induced by complete Freund's adjuvant was accompanied by C5a upregulation and was markedly reduced by C5a receptor (C5aR1) knock-out or treatment with the C5aR1 antagonist PMX53. Direct administration of C5a into the mouse hindpaw produced strong thermal hyperalgesia, an effect that was absent in TRPV1 knock-out mice, and was blocked by the TRPV1 antagonist AMG9810. Immunohistochemistry of mouse plantar skin showed prominent expression of C5aR1 in macrophages. Additionally, C5a evoked strong Ca2+mobilization in macrophages. Macrophage depletion in transgenic macrophage Fas-induced apoptosis mice abolished C5a-dependent thermal hyperalgesia. Examination of inflammatory mediators following C5a injection revealed a rapid upregulation of NGF, a mediator known to sensitize TRPV1. Preinjection of an NGF-neutralizing antibody or Trk inhibitor GNF-5837 prevented C5a-induced thermal hyperalgesia. Notably, NGF-induced thermal hyperalgesia was unaffected by macrophage depletion. Collectively, these results suggest that complement fragment C5a induces thermal hyperalgesia by triggering macrophage-dependent signaling that involves mobilization of NGF and NGF-dependent sensitization of TRPV1. Our findings highlight the importance of macrophage-to-neuron signaling in pain processing and identify C5a, NGF, and TRPV1 as key players in this cross-cellular communication.

SIGNIFICANCE STATEMENTThis study provides mechanistic insight into how the complement system, a key component of innate immunity, regulates the development of pain hypersensitivity. We demonstrate a crucial role of the C5a receptor, C5aR1, in the development of inflammatory thermal and mechanical sensitization. By focusing on the mechanisms of C5a-induced thermal hyperalgesia, we show that this process requires recruitment of macrophages and initiation of macrophage-to-nociceptor signaling. At the molecular level, we demonstrate that this signaling depends on NGF and is mediated by the heat-sensitive nociceptive channel TRPV1. This deeper understanding of how immune cells and neurons interact to regulate pain processing is expected to facilitate mechanism-based approaches in the development of new analgesics.
Cannabidiol Counteracts Amphetamine-Induced Neuronal and Behavioral Sensitization of the Mesolimbic Dopamine Pathway through a Novel mTOR/p70S6 Kinase Signaling Pathway
Authors: Renard Justine , Loureiro Michael , Rosen Laura G. , Zunder Jordan , de Oliveira Cleusa , Schmid Susanne , Rushlow Walter J. , Laviolette Steven R.
Published: May 2016

Schizophrenia-related psychosis is associated with disturbances in mesolimbic dopamine (DA) transmission, characterized by hyperdopaminergic activity in the mesolimbic pathway. Currently, the only clinically effective treatment for schizophrenia involves the use of antipsychotic medications that block DA receptor transmission. However, these medications produce serious side effects leading to poor compliance and treatment outcomes. Emerging evidence points to the involvement of a specific phytochemical component of marijuana called cannabidiol (CBD), which possesses promising therapeutic properties for the treatment of schizophrenia-related psychoses. However, the neuronal and molecular mechanisms through which CBD may exert these effects are entirely unknown. We used amphetamine (AMPH)-induced sensitization and sensorimotor gating in rats, two preclinical procedures relevant to schizophrenia-related psychopathology, combined within vivosingle-unit neuronal electrophysiology recordings in the ventral tegmental area, and molecular analyses to characterize the actions of CBD directly in the nucleus accumbens shell (NASh), a brain region that is the current target of most effective antipsychotics. We demonstrate that Intra-NASh CBD attenuates AMPH-induced sensitization, both in terms of DAergic neuronal activity measured in the ventral tegmental area and psychotomimetic behavioral analyses. We further report that CBD controls downstream phosphorylation of the mTOR/p70S6 kinase signaling pathways directly within the NASh. Our findings demonstrate a novel mechanism for the putative antipsychotic-like properties of CBD in the mesolimbic circuitry. We identify the molecular signaling pathways through which CBD may functionally reduce schizophrenia-like neuropsychopathology.

SIGNIFICANCE STATEMENTThe cannabis-derived phytochemical, cannabidiol (CBD), has been shown to have pharmacotherapeutic efficacy for the treatment of schizophrenia. However, the mechanisms by which CBD may produce antipsychotic effects are entirely unknown. Using preclinical behavioral procedures combined with molecular analyses andin vivoneuronal electrophysiology, our findings identify a functional role for the nucleus accumbens as a critical brain region whereby CBD can produce effects similar to antipsychotic medications by triggering molecular signaling pathways associated with the effects of classic antipsychotic medications. Specifically, we report that CBD can attenuate both behavioral and dopaminergic neuronal correlates of mesolimbic dopaminergic sensitization, via a direct interaction with mTOR/p70S6 kinase signaling within the mesolimbic pathway.
Effects of Electrical Stimulation in the Inferior Colliculus on Frequency Discrimination by Rhesus Monkeys and Implications for the Auditory Midbrain Implant
Authors: Pages Daniel S. , Ross Deborah A. , Puñal Vanessa M. , Agashe Shruti , Dweck Isaac , Mueller Jerel , Grill Warren M. , Wilson Blake S. , Groh Jennifer M.
Published: May 2016

Understanding the relationship between the auditory selectivity of neurons and their contribution to perception is critical to the design of effective auditory brain prosthetics. These prosthetics seek to mimic natural activity patterns to achieve desired perceptual outcomes. We measured the contribution of inferior colliculus (IC) sites to perception using combined recording and electrical stimulation. Monkeys performed a frequency-based discrimination task, reporting whether a probe sound was higher or lower in frequency than a reference sound. Stimulation pulses were paired with the probe sound on 50% of trials (0.5–80 μA, 100–300 Hz,n= 172 IC locations in 3 rhesus monkeys). Electrical stimulation tended to bias the animals' judgments in a fashion that was coarsely but significantly correlated with the best frequency of the stimulation site compared with the reference frequency used in the task. Although there was considerable variability in the effects of stimulation (including impairments in performance and shifts in performance away from the direction predicted based on the site's response properties), the results indicate that stimulation of the IC can evoke percepts correlated with the frequency-tuning properties of the IC. Consistent with the implications of recent human studies, the main avenue for improvement for the auditory midbrain implant suggested by our findings is to increase the number and spatial extent of electrodes, to increase the size of the region that can be electrically activated, and to provide a greater range of evoked percepts.

SIGNIFICANCE STATEMENTPatients with hearing loss stemming from causes that interrupt the auditory pathway after the cochlea need a brain prosthetic to restore hearing. Recently, prosthetic stimulation in the human inferior colliculus (IC) was evaluated in a clinical trial. Thus far, speech understanding was limited for the subjects and this limitation is thought to be partly due to challenges in harnessing the sound frequency representation in the IC. Here, we tested the effects of IC stimulation in monkeys trained to report the sound frequencies they heard. Our results indicate that the IC can be used to introduce a range of frequency percepts and suggest that placement of a greater number of electrode contacts may improve the effectiveness of such implants.
The Proinflammatory Cytokine Interleukin 18 Regulates Feeding by Acting on the Bed Nucleus of the Stria Terminalis
Authors: Francesconi Walter , Sánchez-Alavez Manuel , Berton Fulvia , Alboni Silvia , Benatti Cristina , Mori Simone , Nguyen William , Zorrilla Eric , Moroncini Gianluca , Tascedda Fabio , Conti Bruno
Published: May 2016

The proinflammatory cytokine IL-18 has central anorexigenic effects and was proposed to contribute to loss of appetite observed during sickness. Here we tested in the mouse the hypothesis that IL-18 can decrease food intake by acting on neurons of the bed nucleus of the stria terminalis (BST), a component of extended amygdala recently shown to influence feeding via its projections to the lateral hypothalamus (LH). We found that both subunits of the heterodimeric IL-18 receptor are highly expressed in the BST and that local injection of recombinant IL-18 (50 ng/ml) significantly reduced c-fos activation and food intake for at least 6 h. Electrophysiological experiments performed in BST brain slices demonstrated that IL-18 strongly reduces the excitatory input on BST neurons through a presynaptic mechanism. The effects of IL-18 are cell-specific and were observed in Type III but not in Type I/II neurons. Interestingly, IL-18-sensitve Type III neurons were recorded in the juxtacapsular BST, a region that contains BST-LH projecting neurons. Reducing the excitatory input on Type III GABAergic neurons, IL-18 can increase the firing of glutamatergic LH neurons through a disinhibitory mechanism. Imbalance between excitatory and inhibitory activity in the LH can induce changes in food intake. Effects of IL-18 were mediated by the IL-18R because they were absent in neurons from animals null for IL-18Rα (Il18ra−/−), which lack functional IL-18 receptors. In conclusion, our data show that IL-18 may inhibit feeding by inhibiting the activity of BST Type III GABAergic neurons.

SIGNIFICANCE STATEMENTLoss of appetite during sickness is a common and often debilitating phenomenon. Although proinflammatory cytokines are recognized as mediators of these anorexigenic effects, their mechanism and sites of action remain poorly understood. Here we show that interleukin 18, an anorexigenic cytokine, can act on neurons of the bed nucleus of the stria terminalis to reduce food intake via the IL-18 receptor. The findings identify a site and a mode of action that indicate targets for the treatment of cachexia or other eating disorders.
Ventromedial Prefrontal Cortex Damage Is Associated with Decreased Ventral Striatum Volume and Response to Reward
Authors: Pujara Maia S. , Philippi Carissa L. , Motzkin Julian C. , Baskaya Mustafa K. , Koenigs Michael
Published: May 2016

The ventral striatum and ventromedial prefrontal cortex (vmPFC) are two central nodes of the “reward circuit” of the brain. Human neuroimaging studies have demonstrated coincident activation and functional connectivity between these brain regions, and animal studies have demonstrated that the vmPFC modulates ventral striatum activity. However, there have been no comparable data in humans to address whether the vmPFC may be critical for the reward-related response properties of the ventral striatum. In this study, we used fMRI in five neurosurgical patients with focal vmPFC lesions to test the hypothesis that the vmPFC is necessary for enhancing ventral striatum responses to the anticipation of reward. In support of this hypothesis, we found that, compared with age- and gender-matched neurologically healthy subjects, the vmPFC-lesioned patients had reduced ventral striatal activity during the anticipation of reward. Furthermore, we observed that the vmPFC-lesioned patients had decreased volumes of the accumbens subregion of the ventral striatum. Together, these functional and structural neuroimaging data provide novel evidence for a critical role for the vmPFC in contributing to reward-related activity of the ventral striatum. These results offer new insight into the functional and structural interactions between key components of the brain circuitry underlying human affective function and decision-making.

SIGNIFICANCE STATEMENTMaladaptive decision-making is a common problem across multiple mental health disorders. Developing new pathophysiologically based strategies for diagnosis and treatment thus requires a better understanding of the brain circuits responsible for adaptive decision-making and related psychological subprocesses (e.g., reward valuation, anticipation, and motivation). Animal studies provide evidence that these functions are mediated through direct interactions between two key nodes of a posited “reward circuit,” the ventral striatum and the ventromedial prefrontal cortex (vmPFC). For the first time in humans, we demonstrate that damage to the vmPFC results in decreased ventral striatum activity during reward anticipation. These data provide unique evidence on the causal mechanisms by which the vmPFC and ventral striatum interact during the anticipation of rewards.
The Insula Mediates Access to Awareness of Visual Stimuli Presented Synchronously to the Heartbeat
Authors: Salomon Roy , Ronchi Roberta , Dönz Jonathan , Bello-Ruiz Javier , Herbelin Bruno , Martet Remi , Faivre Nathan , Schaller Karl , Blanke Olaf
Published: May 2016

The processing of interoceptive signals in the insular cortex is thought to underlie self-awareness. However, the influence of interoception on visual awareness and the role of the insular cortex in this process remain unclear. Here, we show in a series of experiments that the relative timing of visual stimuli with respect to the heartbeat modulates visual awareness. We used two masking techniques and show that conscious access for visual stimuli synchronous to participants' heartbeat is suppressed compared with the same stimuli presented asynchronously to their heartbeat. Two independent brain imaging experiments using high-resolution fMRI revealed that the insular cortex was sensitive to both visible and invisible cardio–visual stimulation, showing reduced activation for visual stimuli presented synchronously to the heartbeat. Our results show that interoceptive insular processing affects visual awareness, demonstrating the role of the insula in integrating interoceptive and exteroceptive signals and in the processing of conscious signals beyond self-awareness.

SIGNIFICANCE STATEMENTThere is growing evidence that interoceptive signals conveying information regarding the internal state of the body influence perception and self-awareness. The insular cortex, which receives sensory inputs from both interoceptive and exteroceptive sources, is thought to integrate these multimodal signals. This study shows that cardiac interoceptive signals modulate awareness for visual stimuli such that visual stimuli occurring at the cardiac frequency take longer to access visual awareness and are more difficult to discriminate. Two fMRI experiments show that the insular region is sensitive to this cardio–visual synchrony even when the visual stimuli are rendered invisible through interocular masking. The results indicate a perceptual and neural suppression for visual events coinciding with cardiac interoceptive signals.
Inhibition of the JAK/STAT Pathway Protects Against α-Synuclein-Induced Neuroinflammation and Dopaminergic Neurodegeneration
Authors: Qin Hongwei , Buckley Jessica A. , Li Xinru , Liu Yudong , Fox Thomas H. , Meares Gordon P. , Yu Hao , Yan Zhaoqi , Harms Ashley S. , Li Yufeng , Standaert David G. , Benveniste Etty N.
Published: May 2016

Parkinson's Disease (PD) is an age-related, chronic neurodegenerative disorder. At present, there are no disease-modifying therapies to prevent PD progression. Activated microglia and neuroinflammation are associated with the pathogenesis and progression of PD. Accumulation of α-synuclein (α-SYN) in the brain is a core feature of PD and leads to microglial activation, inflammatory cytokine/chemokine production, and ultimately to neurodegeneration. Given the importance of the JAK/STAT pathway in activating microglia and inducing cytokine/chemokine expression, we investigated the therapeutic potential of inhibiting the JAK/STAT pathway using the JAK1/2 inhibitor, AZD1480.In vitro, α-SYN exposure activated the JAK/STAT pathway in microglia and macrophages, and treatment with AZD1480 inhibited α-SYN-induced major histocompatibility complex Class II and inflammatory gene expression in microglia and macrophages by reducing STAT1 and STAT3 activation. Forin vivostudies, we used a rat model of PD induced by viral overexpression of α-SYN. AZD1480 treatment inhibited α-SYN-induced neuroinflammation by suppressing microglial activation, macrophage and CD4+T-cell infiltration and production of proinflammatory cytokines/chemokines. Numerous genes involved in cell–cell signaling, nervous system development and function, inflammatory diseases/processes, and neurological diseases are enhanced in the substantia nigra of rats with α-SYN overexpression, and inhibited upon treatment with AZD1480. Importantly, inhibition of the JAK/STAT pathway prevented the degeneration of dopaminergic neuronsin vivo. These results indicate that inhibiting the JAK/STAT pathway can prevent neuroinflammation and neurodegeneration by suppressing activation of innate and adaptive immune responses to α-SYN. Furthermore, this suggests the feasibility of targeting the JAK/STAT pathway as a neuroprotective therapy for neurodegenerative diseases.

SIGNIFICANCE STATEMENTα-SYN plays a central role in the pathophysiology of PD through initiation of neuroinflammatory responses. Using an α-SYN overexpression PD model, we demonstrate a beneficial therapeutic effect of AZD1480, a specific inhibitor of JAK1/2, in suppressing neuroinflammation and neurodegeneration. Our findings document that inhibition of the JAK/STAT pathway influences both innate and adaptive immune responses by suppressing α-SYN-induced microglia and macrophage activation and CD4+T-cell recruitment into the CNS, ultimately suppressing neurodegeneration. These findings are the first documentation that suppression of the JAK/STAT pathway disrupts the circuitry of neuroinflammation and neurodegeneration, thus attenuating PD pathogenesis. JAK inhibitors may be a viable therapeutic option for the treatment of PD patients.
Autoethnography in an Almond Grove
Authors: Gingrich-Philbrook Craig
Published: May 2016

The author offers a deconstructive reading of the distinction between “analytic” and “evocative” autoethnography, situating it as a shibboleth that, while useful to many, is often performed in ways that resemble the homophobic “concern” about the consequences of equality. He situates this deconstruction within a larger tale about the almond grove at the edge of his grandparents’ property and a reflection on the confirmation his grandmother gave him.
On Being at Home with Myself
Authors: Boylorn Robin M.
Published: May 2016

The author uses a metaphor of home to discuss and situate a way of being in and seeing/experiencing the world through a raced and gendered lens. She uses what she calls blackgirl autoethnography to talk about embodied, critical, and culturally situated research that begins (and/or) ends at home, in the bodies we live with, and the social circumstances we live through. Using sensory data and preliminary interviews with women she has shared “home” spaces with, she incorporates intersectionality (Crenshaw, 1991), cultural representation (Hall, 2003), endarkened epistemology (Dillard, 2000), and critical autoethnography (Adams, Holman Jones, & Ellis, 2015; Boylorn & Orbe, 2014; Madison, 2012) to argue for blackgirl autoethnography as a praxis for black and brown women to do the home/work of self-construction, absent the influences of racist, classist, and misogynistic culture.
Delusions, Measures, and Presence
Authors: Pelias Ronald J.
Published: May 2016

In anticipation of my mother's death, I write trying to keep her with me, trying to forestall the inevitable. I write to expose the delusions I maintain, to understand how my mother measures the closeness of her death, and to face the conflictual feelings I have in her presence. Writing becomes a method for dealing what is before me.
Cosmic Philosophy and the Arts
Authors: Huss Boaz
Published: May 2016

This article discusses the nexus between art and occultism in the Idéal et Réalité group, which was active in Paris in the third decade of the twentieth century and attracted many prominent writers, poets, actors, and artists. The Idéal et Réalité group emerged from the early twentieth-century esoteric Le Mouvement Cosmique, and it was much influenced by its Cosmic Philosophy. The Cosmic Movement was founded by Max Théon and his wife Théona (Mary Ware) in the first decade of the twentieth century. Art and literature were important in the philosophy and practice of both the Cosmic Movement and the Idéal et Réalité circle. Art dealer Eugène Blot and members of his extended family contributed to the participation of high-profile artists in the Idéal et Réalité circle.
Influence of Emanuel Swedenborg’s Religious Writings on Three Visual Artists
Authors: Williams-Hogan Jane
Published: May 2016

Emanuel Swedenborg (1688–1772) claimed to be an eyewitness to the Apocalypse. Called to be “Servant of the Lord,” he wrote eighteen works in which he defined a new Christianity. While he never formed a church, he distributed his books widely throughout Europe. They stimulated some people to found new religious organizations, some to write in new poetic and literary forms, and others to revolutionize sculpture and painting. These artists found in Swedenborg’s works a vibrant source of a new aesthetic vision. The elements of Swedenborg’s theology that helped to shape that new aesthetic are presented here, as well as the application of different aspects of it in the works of three artists: the English sculptor John Flaxman (1755–1826); the French Symbolist painter Paul Gauguin (1848–1903); and American sculptor Lee Bontecou (b. 1931). Each artist attempts to capture the spiritual reality that Swedenborg portrayed as existing behind and within the natural phenomenal world.
The genes of reproductive system of Сapsicum genus and the search for ways of their application in conditions of covered soil in Ukraine
Authors: Kravchenko V. , Stepenko T.
Published: May 2016

Pepper (Capsicum genus) is one of the most important vegetables and spices in the world. There is constant work in studying the genetics of pepper. New genes and genetic markers are discovered, previously discovered ones are studied in a fi ner detail. Aim. The aim of this work was to describe and systematize currently known genes of the reproductive system of Capsicum genus plants and to highlight the issue of using recessive mutant genes in the selection process while creating new varieties and hybrids of sweet pepper. Methods. The world collection of sweet pepper, current varieties and hybrids of different countries, our own selection material was used to classify reproductive genes in the selective studies. The experiments were conducted in conditions of plastic and glass greenhouses according to modern methods. Results. The data obtained were systematized into the following groups of genes: functional and genetic sterility, cytoplasmic male sterility, fertility restora- tion, female fertility and the ones, responsible for fl owering processes. A part of described genes may be used in heterosis plant breeding and while creating the original initial material. The examples of using recessive mutant genes while creating new varieties and hybrids of sweet pepper were presented along with their short characteristics. New varieties and hybrids of sweet pepper were introduced into the State register of varieties of plants, suitable for growing in Ukraine. Conclusions. The characterized genes may be used in genetic and selection studies. A number of new commercial varieties and hybrids of sweet pepper were created using reces- sive mutant genes.
Practical methodology of assessing probability of establishment of adventive plant pests
Authors: Klechkovskyi Yu. , Titova L. , Palahina О. , Pylypenko L. , Orlinski А.
Published: May 2016

Aim. To develop practical methodology of assessing the probability of establishment of adventive pests out- side of their native range of distribution, using specialized software. Methods. International standards for pest risk analysis ISPM No. 2, ISPM No. 11, ISPM No. 21, РМ 5/1(1), РМ 5/2(2), РМ 5/3(5), РМ 5/5(1) and Agro Atlas (Afonin et al., 2008), MapInfo v.11.0 (Pitney Bowes) and Idrisi Taiga (Сlarklabs) software. Results. The presence of host-plant species range and the correspondence of ecoclimatic conditions of Ukraine (as a pest risk analysis area) to the climate indices of the current area of distribution of such pests as Oemona hirta (lemon tree borer) and Thaumatotibia leucotreta (false codling moth) were studied using specifi ed software. The potential areas of establishment of these pests in Ukraine were defi ned. Conclusions. The effi ciency and convenience of me-thods of assessing the risk of establishment of adventive plant pests using Agro Atlas, MapInfo v.11.0 and Idrisi Taiga software,
were proven. It was determined that a potential area of establishment of O. hirta is the sou-thern part of Odessa region, an inconsiderable part of south-west of Mykolayiv region, south-western territory of Kherson region and almost the entire territory of the Crimean Peninsula. A potential area of establishment of T. leucotreta is an inconsiderable territory of the Black Sea coast − Tarkhankut Penin- sula and Kerch Peninsula in the Crimea.
A Spherically Symmetric Solution of \(R+\lambda R^2\) Gravity
Authors: Thang Bui Quyet , Huong Do Thi
Published: May 2016

We shortly review the metric formalism for the \(f(R)\)  gravity.  Based on the metric formalism, westudy the spherically symmetric static empty space solutions with the gravity Lagrangian\(L=R+\lambda R^2\). We found the general metric that described the static empty space with thespherically symmetry.  Our result is more general than Schwarzschild  solution, specially thepredicted metric is perturbed Schwarzschild metric of the Einstein theory.
A Short Pulse, Narrow Band Distributed Feedback Dye Laser Using Nanoparticle-doped Dye Solution Active Medium
Authors: An Nguyen Thi My , Lien Nghiem Thi Ha , Duong Vu , Thuy Nguyen Thanh , Hoa Do Quang
Published: May 2016

Spherical gold nanoparticles doped dye solution was used for laser active medium. Fluorescence and absorption spectral shapes of laser dye molecules were modified by the resonance energy transfer between gold nanoparticles due to localized surface plasmon effect. Laser pulse width and tuning range of a distributed feedback dye laser can be controlled by using various gold nanoparticle concentrations. The gold nanoparticles can be considered as a quenching element inside laser cavity to remove relaxation oscillation pulses at high pumping rate above threshold.
Study of the \(^{nat}\)Sm\((\gamma ,xn)^{143m,g}\)Sm Reactions Induced by Bremsstrahlung with End-point Energies Just above GDR Region
Authors: Khue Pham Duc , Do Nguyen Van
Published: May 2016

We investigate the energy dependence of the isomeric yield ratios for the \(^{nat}\)Sm\((\gamma ,xn)^{143m,g}\)Sm reactions with bremsstrahlung energies of 40-, 45-, and 50-MeV, just above the giant dipole resonance (GDR) region by the off-line $\gamma $-ray spectrometric method. The bremsstrahlung photons were produced from the 100 MeV electron linear accelerator (linac) at the Pohang accelerator laboratory (PAL), Pohang, Korea. In order to improve the accuracy of the experimental results the necessary corrections were made. The present results are compared with similar literature data of the $^{nat}$Sm($\gamma $,xn)$^{143m,g}$Sm reactions measured at various photon energies and of the $^{nat}$Sm(n,2n)$^{143m,g}$Sm reaction induced by 14 MeV neutrons in order to examine the effects of an excitation energy and an input angular momentum.
Influence of Surface Plasmon Resonance on Fluorescence Emission of Dye-doped Nanoparticles
Authors: Ha Chu Viet , Brochon J. C. , Nhung Tran Hong
Published: May 2016

The influence of the surface plasmon of gold nanoparticles on the optical properties of the fluorescent nanoparticles in aqueous solution have been investigated. The fluorescence of nanoparticles can be enhanced or quenched in the presence of gold nanoparticles depending on the domination of energy transfer mechanisms: radiating surface plasmon coupling emission or F\"{o}rster energy transfer from fluorescent particles to gold particles, which exciting absorbing plasmon. The fluorescence enhancement or quenching is attributed to the increase or decrease of radiative recombination rates, respectively. The parameters of the energy transfer between fluorescent nanoparticles (dye molecules encapsulated in silica nanoparticles) and nano golds have been estimated. The results show that the interactions between nanoparticles depend on the size of both fluorophores (as donors) and gold nanoparticles (as acceptors).
Fluorescent Properties of Cancerous Liver Tissue
Authors: Van Nguyen Thi Khanh , Hoang Nguyen Dinh , Binh Nguyen Thanh , Thanh Nguyen Cong , Binh Pham Kim
Published: May 2016

Fluorescence spectroscopy is a technology used fruitfully for biomedical diagnostics as well as for therapeutic purposes. The fluorescent analysis method are applied in biomedical diagnosticsbases on fluorescence of endogenous or exogenous fluorophores. We initially applied fluorescence spectroscopy for the study of human liver cancer (hepatocellular carcinoma) with an exogenous fluorophores, Radachlorin\(^{\circledR }\) 0.35%. The main aim of this study is to determine the spectral variation between normal and malignant liver tissues in 2 cases: the samples expose and non-expose to Radachlorin. The excitation wavelength used for the fluorescence measurements is 405 nm.
Inverted neutrino mass hierarchy and mixing in the Zee-Babu model
Authors: Vien Vo Van , Long Hoang Ngoc , Thu Phan Ngoc
Published: May 2016

We show that the neutrino mass matrix of the Zee-Babu model isable to fit the recent data on neutrino masses and mixingwith non-zero $\theta_{13}$ in the inverted neutrino mass hierarchy. The results show that the Majorana  phases are equal to zero and the Dirac phase ($\de$) ispredicted to either $0$ or $\pi$, i. e, there is no CP violation in the Zee-Babu model at the two loop level. The effective mass governingneutrinoless double beta decay and the sum of neutrino masses areconsistent with the recent analysis.
Gravitational Waveforms from Multiple-Orbit Simulations of Binary Neutron Stars
Authors: Lan Nguyen Quynh , Suh In-Saeng , Mathews Grant J , Haywood Reese
Published: May 2016

We study the gravitational wave emission of equal-mass neutron stars in binary orbits as the stars approach the inner most last stable circular orbit. We illustrate the extraction of gravitational wave forms in a sequence of quasi-circular orbit simulations including the general relativistic hydrodynamic response of the stars. We compare the computed results with the Newtonian and post Newtonian results and show that substantial differences can arise as the orbits approach the final inspiral.
QUALIDADE DE GOIABAS ‘PEDRO SATO’ EM FUNÇÃO DE TRATAMENTOS ALTERNATIVOS EM PÓS-COLHEITA
Authors: PALHARINI MARIA CECÍLIA DE ARRUDA , FISCHER IVAN HERMAN , ALVES AGHATA REGINA DE OLIVEIRA FERREIRA , FILETI MIRIAN DE SOUZA , NOGUEIRA JÚNIOR ANTÔNIO FERNANDES
Published: May 2016

RESUMO Este trabalho teve como objetivo avaliar o efeito de produtos alternativos e termoterapia, isoladamente e em associação, na qualidade físico-química e no controle das podridões de goiabas ‘Pedro Sato’. Inicialmente, foi avaliado o efeito dos tratamentos em pós-colheita com cloreto de cálcio, fosfito de potássio, 1-metilciclopropeno (1-MCP), fécula de mandioca, etanol seguido de cloro (etanol+cloro) e termoterapia, durante oito dias de armazenamento dos frutos a 22ºC. Em uma segunda etapa, quatro tratamentos foram selecionados (fécula de mandioca, 1-MCP, termoterapia e etanol+cloro) e avaliados em associação de dois, aplicados de forma sequencial, durante oito dias de armazenamento dos frutos a 25ºC. Os tratamentos 1-MCP e fécula foram os mais eficazes em manter a qualidade físico-química das goiabas ‘Pedro Sato’, retardando a perda de massa, a mudança de coloração da casca e contribuindo para a retenção da firmeza. Constatou-se maior redução de frutos com podridão nos tratamentos com termoterapia, fécula de mandioca e 1-MCP. As associações de tratamento com 1-MCP/fécula de mandioca e termoterapia/fécula foram os tratamentos mais eficazes em manter a qualidade das goiabas ‘Pedro Sato’, retardando a perda de massa, a mudança de coloração da casca e a redução da firmeza. As associações de tratamento reduziram a ocorrência de podridões, com destaque para os tratamentos com etanol+cloro/termoterapia e termoterapia/fécula, que foram mais eficientes até o quarto dia de armazenamento. Observou-se correlação entre a incidência de podridões e os parâmetros cor da casca e firmeza da polpa para a maioria das associações de tratamentos. De maneira geral, recomenda-se o tratamento com termoterapia/fécula para goiabas armazenadas a 22-25ºC, como forma de manutenção da qualidade físico-química e atrasando em, pelo menos, dois dias os sintomas de podridões.
PROTETOR SOLAR DIMINUI A INCIDÊNCIA DAS PODRIDÕES ‘OLHO-D-BOI’ E ‘BRANCA’ EM MAÇÃS ‘FUJI STANDARD’ E ‘PINK LADY’
Authors: VALDEBENITO-SANHUEZA ROSA MARIA , CANTILLANO RUFINO FERNANDO FLORES , BARTNICKI VINÍCIUS ADÃO , SPOLTI PIÉRRI
Published: May 2016

RESUMO A podridão-olho-de-boi (Cryptosporiosis perennans) e a podridão-branca (Botryosphaeria dothidea) estão entre as principais doenças de verão da macieira no Brasil. O objetivo deste trabalho foi avaliar o efeito de uma película protetora constituída de cera de carnaúba e argilas (Raynox® ), nas doses de 2,5 e 5,0%, na infecção por C. perennans e por B. dothidea em maçãs das cultivares Fuji Standard e Pink Lady. As macieiras foram pulverizadas cinco vezes de dezembro de 2007 a março de 2008, conforme previsão de condições adequadas para ocorrência dos danos e crescimento dos frutos. Na colheita, as maçãs foram inoculadas com os dois patógenos e avaliadas quanto à incidência das podridões. Indiferente à dose, o uso de Raynox® reduziu a incidência da podridão-branca e da podridão-olho-de-boi em 67% e 42% na ‘Fuji Standard’, e 43% e 42% na ‘Pink Lady’, respectivamente. O incremento da dose aumentou a eficiência do produto para o controle da podridão-olho-de-boi. Na dose de 2,5%, o controle da podridão-olho-de-boi foi de 19% e 20%, respectivamente, em maçãs ‘Fuji Standard’ e ‘Pink Lady’, enquanto para as mesmas cultivares, mas com a dose de 5,0%, estes valores foram de 65% e 63%. Mais estudos são necessários para o ajuste de dose e critérios de aplicação para que o protetor solar possa ser recomendado.
EFEITO DE FUNGOS MICORRÍZICOS ARBUSCULARES E DA ADUBAÇÃO NO CRESCIMENTO DE MUDAS DE Eugenia uniflora L., PRODUZIDAS EM DIFERENTES SUBSTRATOS
Authors: DALANHOL SAMANTA JAQUELINE , NOGUEIRA ANTONIO CARLOS , GAIAD SÉRGIO , KRATZ DAGMA
Published: May 2016

RESUMO O objetivo deste estudo foi avaliar o efeito de fungos micorrízicos arbusculares (FMAs), da adubação e da composição do substrato no crescimento de mudas de Eugenia uniflora. As sementes foram germinadas em vermiculita média e repicadas para tubetes (100 cm3) contendo substratos à base de vermicomposto e casca de arroz carbonizada e, como controle, utilizou-se do substrato comercial à base de casca de pínus. Estes substratos foram testados com e sem inoculação micorrízica, adicionada ao substrato, como também se testaram a presença e a ausência de adubação de cobertura. Foram analisadas as propriedades físico-químicas dos substratos formulados. Avaliaram-se a altura, o diâmetro do colo, a agregação das raízes ao substrato, a biomassa seca aérea, a biomassa seca radicial e foram determinados a relação entre altura e diâmetro do colo e o índice de qualidade de Dickson. A inoculação com FMAs não influenciou no crescimento das mudas, enquanto a interação entre substratos e adubação foi significativa para a maioria das variáveis. A ausência de resposta aos FMAs foi, provavelmente, devido às altas concentrações de fósforo nestes substratos. Concluiu-se que o substrato à base de vermicomposto e casca de arroz carbonizada, na proporção de 20/80, pode ser utilizado na produção de mudas desta espécie.
DESENVOLVIMENTO, FISIOLOGIA DA MATURAÇÃO E INDICADORES DO PONTO DE COLHEITA DE FRUTOS DA UMBUGUELEIRA (Spondias sp.)
Authors: DANTAS ANA LIMA , SILVA SILVANDA DE MELO , DANTAS RENATO LIMA , SOUSA ALEX SANDRO BEZERRA DE , SCHUNEMANN ANA PAULA PEREIRA
Published: May 2016

RESUMO A umbugueleira produz frutos com amplas possibilidades de utilização que, embora subexplorados, têm grande potencial socioeconômico. Dessa forma, o objetivo deste estudo foi avaliar o desenvolvimento e a fisiologia da maturação em frutos da umbugueleira. As inflorescências foram marcadas em seis plantas, no período da antese, e o fruto (umbuguela) foi avaliado em intervalos regulares até a abscisão da planta. O ciclo de desenvolvimento da umbuguela, da antese até o início da abscisão, abrange 157 dias; a massa, o volume, o comprimento e o diâmetro apresentam aumentos rápidos até 117 dias após a antese (DAA), estabilizando-se até o final da maturação. O padrão respiratório do fruto foi climatérico, com pico aos 147 DAA. A coloração evoluiu do verde para o amarelo e, no pós-climatério, para o vermelho-púrpura. A relação SS/AT e pH aumentaram, e a AT diminuiu durante a maturação. O ponto ideal de colheita para o armazenamento ocorreu dos 127 aos 137 DAA, com início da coloração amarela a amarelo predominante. Para consumo fresco, o ponto de colheita foi a partir de 147 DAA (amarelo com traços avermelhados).