bluuebunny/crossref_metadata_2025 huggingface dataset:
A Novel Neuron-Enriched Homolog of the Erythrocyte Membrane Cytoskeletal Protein 4.1
Authors: Walensky Loren D. , Blackshaw Seth , Liao Dezhi , Watkins Crystal C. , Weier Heinz-Ulrich G. , Parra Marilyn , Huganir Richard L. , Conboy John G. , Mohandas Narla , Snyder Solomon H.
Published: April 2018

We report the molecular cloning and characterization of 4.1N, a novel neuronal homolog of the erythrocyte membrane cytoskeletal protein 4.1 (4.1R). The 879 amino acid protein shares 70, 36, and 46% identity with 4.1R in the defined membrane-binding, spectrin-actin–binding, and C-terminal domains, respectively. 4.1N is expressed in almost all central and peripheral neurons of the body and is detected in embryonic neurons at the earliest stage of postmitotic differentiation. Like 4.1R, 4.1N has multiple splice forms as evidenced by PCR and Western analysis. Whereas the predominant 4.1N isoform identified in brain is ∼135 kDa, a smaller 100 kDa isoform is enriched in peripheral tissues. Immunohistochemical studies using a polyclonal 4.1N antibody revealed several patterns of neuronal staining, with localizations in the neuronal cell body, dendrites, and axons. In certain neuronal locations, including the granule cell layers of the cerebellum and dentate gyrus, a distinct punctate-staining pattern was observed consistent with a synaptic localization. In primary hippocampal cultures, mouse 4.1N is enriched at the discrete sites of synaptic contact, colocalizing with the postsynaptic density protein of 95 kDa (a postsynaptic marker) and glutamate receptor type 1 (an excitatory postsynaptic marker). By analogy with the roles of 4.1R in red blood cells, 4.1N may function to confer stability and plasticity to the neuronal membrane via interactions with multiple binding partners, including the spectrin-actin–based cytoskeleton, integral membrane channels and receptors, and membrane-associated guanylate kinases.
Cloning and Characterization of Neuropilin-1-Interacting Protein: A PSD-95/Dlg/ZO-1 Domain-Containing Protein That Interacts with the Cytoplasmic Domain of Neuropilin-1
Authors: Cai Huaibin , Reed Randall R.
Published: April 2018

Neuropilin-1 (Npn-1), a receptor for semaphorin III, mediates the guidance of growth cones on extending neurites. The molecular mechanism of Npn-1 signaling remains unclear. We have used a yeast two-hybrid system to isolate a protein that interacts with the cytoplasmic domain of Npn-1. This Npn-1-interacting protein (NIP) contains a central PSD-95/Dlg/ZO-1 (PDZ) domain and a C-terminal acyl carrier protein domain. The physiological interaction of Npn-1 and NIP is supported by co-immunoprecipitation of these two proteins in extracts from a heterologous expression system and from a native tissue. The C-terminal three amino acids of Npn-1 (S-E-A-COOH), which is conserved fromXenopusto human, is responsible for interaction with the PDZ domain-containing C-terminal two-thirds of NIP. NIP as well as Npn-1 are broadly expressed in mice as assayed by Northern and Western analysis. Immunohistochemistry andin situhybridization experiments revealed that NIP expression overlaps with that of Npn-1. NIP has been independently cloned as RGS–GAIP-interacting protein (GIPC), where it was identified by virtue of its interaction with the C terminus of RGS-GAIP and suggested to participate in clathrin-coated vesicular trafficking. We suggest that NIP and GIPC may participate in regulation of Npn-1-mediated signaling as a molecular adapter that couples Npn-1 to membrane trafficking machinery in the dynamic axon growth cone.
Pituitary Adenylate Cyclase Activating Peptide Phase Shifts Circadian Rhythms in a Manner Similar to Light
Authors: Harrington Mary E. , Hoque Sabina , Hall Adam , Golombek Diego , Biello Stephany
Published: April 2018

The endogenous circadian pacemaker in mammals is located in the suprachiasmatic nuclei (SCN) of the hypothalamus. Various cues can reset circadian rhythm phase, thereby entraining the internal rhythm to the environmental cycle, and these effects can be investigated using anin vitromethod to measure phase shifts of the SCN. Although pituitary adenylate cyclase activating peptide (PACAP) is localized in retinal inputs to the SCN, it has been reported to alter clock phase only during the subjective day (Hannibal et al., 1997), whereas light alters phase only in the subjective night. In this study we show that PACAP can reset the clock in the photic pattern during the subjective night when applied in 10 pmto 1 nmdoses. This appears to be mediated via a glutamatergic mechanism, possibly by potentiation of NMDA currents as is seen at 10–100 pm. Given at higher doses (>10 nm), PACAP shifts in the subjective day, apparently via activation of adenylate cyclase and increased intracellular cAMP. These results indicate dose and phase specificity of the effects of PACAP, and a new role as a transmitter in the retinohypothalamic tract.
An Inhibitory Interface Gates Impulse Traffic between the Input and Output Stations of the Amygdala
Authors: Royer Sébastien , Martina Marzia , Paré Denis
Published: April 2018

The central amygdaloid nucleus projects to brainstem and hypothalamic nuclei mediating fear responses and receives convergent sensory inputs from the basolateral amygdaloid complex. However, interposed between the basolateral complex and central nucleus is a string of interconnected GABAergic cell clusters, the intercalated cell masses. Here, we analyzed how intercalated neurons influence impulse traffic between the basolateral complex and central nucleus using whole-cell recordings, microstimulation, and local application of glutamate receptor antagonists in brain slices. Our results suggest that intercalated neurons receive glutamatergic inputs from the basolateral complex and generate feedforward inhibition in neurons of the central nucleus. As the position of the recording site was shifted medially, intercalated cells projected to gradually more medial sectors of the central nucleus and were maximally responsive to progressively more medial stimulation sites in the basolateral complex. Thus, there is a lateromedial correspondence between the position of intercalated cells, their projection site in the central nucleus, and the source of their excitatory afferents in the basolateral complex. In addition, basolateral stimulation sites eliciting maximal excitatory responses in intercalated neurons were flanked laterally by sites eliciting prevalently inhibitory responses via the activation of intercalated cells located more laterally. As a result, the feedforward inhibition generated by intercalated neurons and, indirectly, the amplitude of the responses of central neurons could be increased or decreased depending on which combination of amygdala nuclei are activated and in what sequence. Thus, the output of the central nucleus depends not only on the nature and intensity of sensory inputs but also on their timing and origin.
Identification of Residues within GABAAReceptor α Subunits That Mediate Specific Assembly with Receptor β Subunits
Authors: Taylor Pamela M. , Connolly Christopher N. , Kittler Josef T. , Gorrie George H. , Hosie Alistair , Smart Trevor G. , Moss Stephen J.
Published: April 2018

GABAAreceptors can be constructed from a range of differing subunit isoforms: α, β, γ, δ, and ε. Expression studies have revealed that production of GABA-gated channels is achieved after coexpression of α and β subunits. The expression of a γ subunit isoform is essential to confer benzodiazepine sensitivity on the expressed receptor. However, how the specificity of subunit interactions is controlled during receptor assembly remains unknown. Here we demonstrate that residues 58–67 within α subunit isoforms are important in the assembly of receptors comprised of αβ and αβγ subunits. Deletion of these residues from the α1 or α6 subunits results in retention of either α subunit isoform in the endoplasmic reticulum on coexpression with the β3, or β3 and γ2 subunits. Immunoprecipitation revealed that residues 58–67 mediated oligomerization of the α1 and β3 subunits, but were without affect on the production of α/γ complexes. Within this domain, glutamine 67 was of central importance in mediating the production of functional α1β3 receptors. Mutation of this residue resulted in a drastic decrease in the cell surface expression of α1β3 receptors and the resulting expression of β3 homomers. Sucrose density gradient centrifugation revealed that this residue was important for the production of a 9S α1β3 complex representing functional GABAAreceptors.

Therefore, our studies detail residues that specify GABAAreceptor αβ subunit interactions. This domain, which is conserved in all α subunit isoforms, will therefore play a critical role in the assembly of GABAAreceptors composed of αβ and αβγ subunits.
Molecular Cloning and Functional Characterization of a New Modulatory Cyclic Nucleotide-Gated Channel Subunit from Mouse Retina
Authors: Gerstner Andrea , Zong Xiangang , Hofmann Franz , Biel Martin
Published: April 2018

Cyclic nucleotide-gated (CNG) channels play a key role in olfactory and visual transduction. Native CNG channels are heteromeric complexes consisting of the principal α subunits (CNG1–3), which can form functional channels by themselves, and the modulatory β subunits (CNG4–5). The individual α and β subunits that combine to form the CNG channels in rod photoreceptors (CNG1 + CNG4) and olfactory neurons (CNG2 + CNG4 + CNG5) have been characterized. In contrast, only an α subunit (CNG3) has been identified so far in cone photoreceptors. Here we report the molecular cloning of a new CNG channel subunit (CNG6) from mouse retina. The cDNA of CNG6 encodes a peptide of 694 amino acids with a predicted molecular weight of 80 kDa. Among the CNG channel subunits, CNG6 has the highest overall similarity to the CNG4 β subunit (47% sequence identity). CNG6 transcripts are present in a small subset of retinal photoreceptor cells and also in testis. Heterologous expression of CNG6 in human embryonic kidney 293 cells did not lead to detectable currents. However, when coexpressed with the cone photoreceptor α subunit, CNG6 induced a flickering channel gating, weakened the outward rectification in the presence of extracellular Ca2+, increased the sensitivity forl-cisdiltiazem, and enhanced the cAMP efficacy of the channel. Taken together, the data indicate that CNG6 represents a new CNG channel β subunit that may associate with the CNG3 α subunit to form the native cone channel.
Synaptic Reorganization in the Substantia Gelatinosa After Peripheral Nerve Neuroma Formation: Aberrant Innervation of Lamina II Neurons by Aβ Afferents
Authors: Kohama Ikuhide , Ishikawa Kuniko , Kocsis Jeffery D.
Published: April 2018

Intracellular recording and extracellular field potential (FP) recordings were obtained from spinal cord dorsal horn neurons (laminae I–IV) in a rat transverse slice preparation with attached dorsal roots. To study changes in synaptic inputs after neuroma formation, the sciatic nerve was sectioned and ligated 3 weeks beforein vitroelectrophysiological analysis. Horseradish peroxidase labeling of dorsal root axons indicated that Aβ fibers sprouted into laminae I–II from deeper laminae after sciatic nerve section. FP recordings from dorsal horns of normal spinal cord slices revealed long-latency synaptic responses in lamina II and short-latency responses in lamina III. The latencies of synaptic FPs recorded in lamina II of the dorsal horn after sciatic nerve section were reduced. The majority of monosynaptic EPSPs recorded with intracellular microelectrodes from lamina II neurons in control slices were elicited by high-threshold nerve stimulation, whereas the majority of monosynaptic EPSPs recorded in lamina III were elicited by low-threshold nerve stimulation. After sciatic nerve section, 31 of 57 (54%) EPSPs recorded in lamina II were elicited by low-threshold stimulation. The majority of low-threshold EPSPs in lamina II neurons after axotomy displayed properties similar to low-threshold EPSPs in lamina III of control slices. These results indicate that reoccupation of lamina II synapses by sprouting Aβ fibers normally terminating in lamina III occurs after sciatic nerve neuroma formation. Furthermore, these observations indicate that the lamina II neurons receive inappropriate sensory information from low-threshold mechanoreceptor after sciatic nerve neuroma formation.
Genetic Inactivation of the Serotonin1AReceptor in Mice Results in Downregulation of Major GABAAReceptor α Subunits, Reduction of GABAAReceptor Binding, and Benzodiazepine-Resistant Anxiety
Authors: Sibille Etienne , Pavlides Constantine , Benke Dietmar , Toth Miklos
Published: April 2018

Anxiety is a common psychiatric illness often treated by benzodiazepines (BZs). BZs, such as Valium, bind to the α subunit of the pentameric GABAAreceptor and increase inhibition in the CNS. There is considerable evidence for abnormal GABAAreceptor function in anxiety, and a significant proportion of anxiety patients has a reduced sensitivity to BZs. Here, we show that serotonin1A(5-HT1A) receptor knock-out mice display BZ-resistant anxiety. Consistent with this finding, binding of both BZ and non-BZ GABAAreceptor ligands were reduced and GABAergic inhibition was impaired in mutant mice. These changes were reflected by abnormal α subunit expression in the amygdala and hippocampus, two important limbic regions involved in fear and anxiety. These data suggest a pathological pathway, initiated by a 5-HT1Areceptor deficit, leading to abnormalities in GABAAreceptor composition and level, which in turn result in BZ-insensitivity and anxiety. This model mechanistically links together the 5-HT and GABA systems, which both have been implicated in anxiety. A related mechanism may underlie reduced BZ sensitivity in certain forms of anxiety.
P2Y1Purinoceptor-Mediated Ca2+Signaling and Ca2+Wave Propagation in Dorsal Spinal Cord Astrocytes
Authors: Fam Sami R. , Gallagher Conor J. , Salter Michael W.
Published: April 2018

ATP is known to act as an extracellular messenger mediating the propagation of Ca2+waves in astrocyte networks. ATP mediates Ca2+waves by activating P2Y purinoceptors, which mobilize intracellular Ca2+in astrocytes. A number of P2Y purinoceptor subtypes have been discovered, but it is not known which P2Y subtypes participate in transmitting astrocyte Ca2+waves. Here, we show that ATP analogs that are selective agonists for the P2Y1subtype of purinoceptor caused release of intracellular Ca2+in astrocytes from the dorsal spinal cord. The Ca2+responses were blocked by adenosine-3′-phospho-5′-phosphosulfate, an antagonist known to selectively inhibit P2Y1but not other P2Y purinoceptor subtypes. Also, we show that P2Y1mRNA is expressed in dorsal spinal cord astrocytes. Furthermore, expression of P2Y1in an astrocytoma cell line lacking endogenous purinoceptors was sufficient to permit propagation of intercellular Ca2+waves. Finally, Ca2+wave propagation in dorsal spinal cord astrocytes was suppressed by pharmacologically blocking P2Y1purinoceptors. Together, these results indicate that dorsal spinal astrocytes express functional P2Y1purinoceptors, which participate in the transmission of Ca2+waves. Ca2+waves in astrocytes have been implicated as a major signaling pathway coordinating glial and neuronal activity; therefore, P2Y1purinoceptors may represent an important link in cell–cell signaling in the CNS.
Blockade of Neuronal Activity During Hippocampal Development Produces a Chronic Focal Epilepsy in the Rat
Authors: Galvan Cynthia D. , Hrachovy Richard A. , Smith Karen L. , Swann John W.
Published: April 2018

During brain development, neuronal activity can transform neurons characterized by widely ranging axonal projections to ones with more restricted patterns of synaptic connectivity. Previous studies have shown that an exuberant outgrowth of local recurrent excitatory axons occurs in hippocampal area CA3 during postnatal weeks 2 and 3. Axons are remodeled with maturation, and nearly half of the branches are eliminated. Postnatal weeks 2 and 3 also coincide with a “critical” period of development, when CA3 networks have a marked propensity to generate electrographic seizures. In an attempt to prevent axonal remodeling, local circuit activity was blocked unilaterally in dorsal hippocampus by continuous infusion of tetrodotoxin (TTX). Field potential recordings from behaving animals were dramatically altered when TTX infusion was initiated at the beginning of the critical period, week 2, but not later in life. Spontaneous, synchronized spikes and electrographic seizures with behavioral accompaniments were observed after 4 weeks of TTX infusion and persisted into adulthood. When recordings were made during TTX infusion, synchronized spiking was recorded in ventral hippocampus as early as 2 weeks after infusate introduction. At this same time, extracellular field recordings fromin vitroslices demonstrated spontaneous network-driven “mini-bursts” arising from ventral hippocampal slices. These were abolished by glutamate receptor antagonists. Whole-cell recordings from CA3 neurons revealed bursts of excitatory synaptic potentials coincident with the network bursts recorded extracellularly. Thus, local assemblies of mutually excitatory CA3 pyramidal cells are hyperexcitable in these rats. Whether alterations in developmental axonal remodeling mediate these effects awaits further studies.
Regulation of Glial Cell Line-Derived Neurotrophic Factor Responsiveness in Developing Rat Sympathetic Neurons by Retinoic Acid and Bone Morphogenetic Protein-2
Authors: Thang Siong Heng , Kobayashi Miwako , Matsuoka Ichiro
Published: April 2018

There are several lines of evidence suggesting that, in addition to neurotrophins, member(s) of glial cell line-derived neurotrophic factor (GDNF) family play important roles in the development of sympathetic neurons. However, the mechanism regulating the responsiveness of the neurons to GDNF family members is not known. Previously, we reported on the cooperative roles of bone morphogenetic protein-2 (BMP2) and retinoic acid (RA) in the enhancement of neurotrophin-3 (NT3) responsiveness in cultured sympathetic neurons dissociated from perinatal rat superior cervical ganglia (SCG). In the present study, we further examined the effects of BMP2 and RA on the regulation of the responsiveness of SCG neurons to GDNF family members. Consequently, we found that RA alone induced the responsiveness of SCG neurons specifically to GDNF by upregulating the ligand-specifying receptor for GDNF (GFRα-1) at both the mRNA and protein levels. The expression levels of mRNAs for other ligand-specifying receptors for GDNF family (GFRα-2 and GFRα-3) were unaffected by RA. Although the upregulation of signal-transducing receptor Ret by the RA treatment was rather small, this treatment significantly increased the efficacy of tyrosine phosphorylation of Ret by GDNF. Experiments using synthetic retinoids suggested that RA acts through α-type of nuclear retinoic acid receptor to exert the induction of GDNF responsiveness. On the other hand, BMP2, which had no significant effect by itself on the GDNF responsiveness, promoted the action of RA to upregulate GFRα-1 and enhance the GDNF responsiveness. These results indicate that RA and BMP2 play important roles in the induction of GDNF responsiveness, as well as NT3 responsiveness, of developing SCG neurons.
Circulating Insulin-Like Growth Factor I Mediates Effects of Exercise on the Brain
Authors: Carro Eva , Nuñez Angel , Busiguina Svetlana , Torres-Aleman Ignacio
Published: April 2018

Physical exercise increases brain activity through mechanisms not yet known. We now report that in rats, running induces uptake of blood insulin-like growth factor I (IGF-I) by specific groups of neurons throughout the brain. Neurons accumulating IGF-I show increased spontaneous firing and a protracted increase in sensitivity to afferent stimulation. Furthermore, systemic injection of IGF-I mimicked the effects of exercise in the brain. Thus, brain uptake of IGF-I after either intracarotid injection or after exercise elicited the same pattern of neuronal accumulation of IGF-I, an identical widespread increase in neuronal c-Fos, and a similar stimulation of hippocampal brain-derived neurotrophic factor. When uptake of IGF-I by brain cells was blocked, the exercise-induced increase on c-Fos expression was also blocked. We conclude that serum IGF-I mediates activational effects of exercise in the brain. Thus, stimulation of the uptake of blood-borne IGF-I by nerve cells may lead to novel neuroprotective strategies.
Altered Electromyographic Activity Pattern of Rat Soleus Muscle Transposed into the Bed of Antagonist Muscle
Authors: Slawinska Urszula , Kasicki Stefan
Published: April 2018

Human patients suffering from motor paralysis of the leg can learn, to some extent, how to use the transposed antagonistic muscle in place of the damaged or ineffective muscle. Experiments on animals showed opposite results, although in a few experiments the functional reorganization of the activity of the transposed muscle was not excluded. In our experiments, we performed transposition of the soleus (Sol) with a preserved innervation into the bed of the removed extensor digitorum longus (EDL) in 6-d-old pups and 3-month-old rats. The locomotor and reflex EMG activity of the transposed Sol (trSol) was recorded in chronic experiments 3–4 months later. Our results showed that the EMG activity of the Sol might be modified when the muscle is transposed into the bed of the antagonistic muscle EDL. The modification consisted of an additional burst of activity during the swing phase and of reflex response of the muscle to the plantar flexion. This modification was present in all animals operated on at 6 d of age and in two of six adults. After chronic experiments, we excluded the possibility that the flexor-like activity was induced by additional innervation of the trSol by the cut end of the EDL nerve. We suggest that the observed modifications of activity of trSol might be caused by readjustment of the spinal network organization to the new functional demands. Two factors might be responsible for this readjustment: the immaturity of the nervous system at the moment of surgery and preserved afferent innervation of the transposed muscle.
Rac1-Mediated Endocytosis during Ephrin-A2- and Semaphorin 3A-Induced Growth Cone Collapse
Authors: Jurney William M. , Gallo Gianluca , Letourneau Paul C. , McLoon Steven C.
Published: April 2018

Negative guidance molecules are important for guiding the growth of axons and ultimately for determining the wiring pattern in the developing nervous system. In tissue culture, growth cones at the tips of growing axons collapse in response to negative guidance molecules, such as ephrin-A2 and semaphorin 3A. The small GTPase Rac1 is involved in growth cone collapse, but the nature of its role is not clear. Rac1 activity assays showed that Rac1 is transiently inactivated after treatment with ephrin-A2. Ephrin-induced growth cone collapse, however, correlated with resumption of Rac1 activity. We demonstrate that Rac1 is required for endocytosis of the growth cone plasma membrane and reorganization of F-actin but not for the depolymerization of F-actin during growth cone collapse in response to ephrin-A2 and semaphorin 3A. Rac1, however, does not regulate constitutive endocytosis in growth cones. These findings show that in response to negative guidance molecules, the function of Rac1 changes from promoting actin polymerization associated with axon growth to driving endocytosis of the plasma membrane, resulting in growth cone collapse. Furthermore, Rac1 antisense injected into the embryonic chick eyein vivocaused the retinotectal projection to develop without normal topography in a manner consistent with Rac1 having an obligatory role in mediating ephrin signaling.
A Critical Function of the Pial Basement Membrane in Cortical Histogenesis
Authors: Halfter Willi , Dong Sucai , Yip Yi-Ping , Willem Michael , Mayer Ulrike
Published: April 2018

Mice with a targeted deletion of the nidogen-binding site of laminin γ1 were used to study the function of the pial basement membrane in cortical histogenesis. The pial basement membrane in the mutant embryos assembled but was unstable and disintegrated at random segments. In segments with a disrupted basement membrane, radial glia cells were retracted from the pial surface, and radially migrating neurons, including Cajal-Retzius cells and cortical plate neurons, passed the meninges or terminated their migration prematurely. By correlating the disruptions in the pial basal lamina with changes in the morphology of radial glia cells, the aberrant migration of Cajal-Retzius cells, and subsequent dysplasia of cortical plate neurons, the present data establish a causal relationship of proper cortical histogenesis with the presence of an intact pial basement membrane.
Group I Metabotropic Glutamate Receptor (mGluR)-Dependent Long-Term Depression Mediated via p38 Mitogen-Activated Protein Kinase Is Inhibited by Previous High-Frequency Stimulation and Activation of mGluRs and Protein Kinase C in the Rat Dentate GyrusIn Vitro
Authors: Rush Anthony M. , Wu Jianqun , Rowan Michael J. , Anwyl Roger
Published: April 2018

The induction of synaptic plasticity is known to be influenced by the previous history of the synapse, a process termed metaplasticity. Here we demonstrate a novel metaplasticity in which group I metabotropic glutamate receptor (mGluR)-dependent long-term depression (LTD) of synaptic transmission is regulated by previous mGluR activation. In these studies, the group I mGluR-dependent LTD induced by the selective agonist (RS)-3,5-dihydroxyphenylglycine (DHPG-LTD) was inhibited by previous preconditioning brief high-frequency stimulation (HFS), regardless of whether the preconditioning HFS induced long-term potentiation. Blockade of NMDA receptors during the preconditioning HFS did not alter the inhibition of DHPG-LTD by the HFS. However, antagonism of mGluRs during the preconditioning HFS did prevent the inhibition of DHPG-LTD by the HFS. In addition, blocking PKC stimulation during the preconditioning HFS also prevented the inhibitory effect of HFS on DHPG-LTD. The DHPG-LTD itself was not inhibited by blocking PKC stimulation but was inhibited by blocking the p38 mitogen-activated protein kinase (MAPK) pathway. Thus, whereas the DHPG-LTD is mediated via activation of the p38 MAPK pathway, the inhibitory effects of preconditioning HFS on DHPG-LTD are mediated via stimulation of group I/II mGluRs, activation of PKC, and subsequent blocking of the functioning of group I mGluR.
Biphasic Effects of Cannabinoids on Acetylcholine Release in the Hippocampus: Site and Mechanism of Action
Authors: Tzavara Eleni T. , Wade Mark , Nomikos George G.
Published: April 2018

Cannabinoids have been shown to critically modulate cholinergic neurotransmission in the hippocampus, yet opposing effects of cannabinoid receptor 1 (CB1R) agonists on hippocampal synaptic acetylcholine (ACh) efflux have been reported. This study shows that administration of a synthetic CB1R agonist results in a biphasic, dose-dependent, effect on hippocampal ACh: a low (0.5 mg/kg, i.p.) and a high (5 mg/kg, i.p) dose of WIN55,212-2 induces a transient stimulation and a prolonged inhibition of hippocampal ACh efflux, respectively. Both effects of WIN55,212-2 are mediated through CB1receptors coupled to Gibut involve different neuroanatomical sites. Thus, intrahippocampal infusion of the CB1R antagonist SR141716A or pertussis toxin blocked the inhibition of hippocampal ACh release induced by the high dose of WIN55,212-2, but was without effect on the stimulatory action of the low dose. In contrast, this latter effect was blocked by SR141716A or pertussis toxin infused, in dual microdialysis experiments, in the septum, in which the majority of cholinergic cell bodies projecting to the hippocampus reside. The stimulatory and inhibitory effects of WIN55,212-2 on hippocampal ACh involve dopamine D1and D2receptor activation, respectively, given that pretreatment with D1and D2receptor antagonists prevents the respective actions of WIN55,212-2. We propose that thein vivoobserved biphasic effects of CB1R agonists on hippocampal ACh release result from a differential, functional association of anatomicaly distinct subpopulations of CB1-Gicoupled receptors to neurotransmitter systems that have opposing effects on ACh release. This concept could provide a theoretical framework to understand endocannabinoids as state-dependent modulators of neuronal activity.
Sunburned
Authors: Prasad Pavithra
Published: April 2018

This essay considers how travel and mobility inflect our politics of alterity through changing skin color. It asks how globality is rendered through the prism of epidermal vulnerability, the sunburn. When is this affliction of skin desirable and what cosmopolitan relations does it engender? It asks how skin transforms, and transforms us, when it travels. It considers what it means for brown skin to be marked by vacation travel. How is it coded differently than tanned white skin? What experiences are ascribed or denied to brown skin that has been marked by travel under the sun?
Improving Anaphylaxis Care: The Impact of a Clinical Pathway
Authors: Lee Juhee , Rodio Bonnie , Lavelle Jane , Lewis Megan Ott , English Rachel , Hadley Sarah , Molnar Jennifer , Jacobstein Cynthia , Cianferoni Antonella , Spergel Jonathan , Zielinski Lisa , Tsarouhas Nicholas , Brown-Whitehorn Terri
Published: April 2018

BACKGROUND:

Recommended durations of observation after anaphylaxis have been widely variable, with many ranging from 4 to 24 hours. Prolonged durations often prompt admission for ongoing observation.

METHODS:

In a multidisciplinary quality improvement initiative, we revised our emergency department (ED) anaphylaxis clinical pathway. Our primary aim was to safely decrease the recommended length of observation from 8 to 4 hours and thereby decrease unnecessary hospitalizations. Secondary aims included provider education on anaphylaxis diagnostic criteria, emphasizing epinephrine as first-line therapy, and implementing a practice of discharging ED patients with an epinephrine autoinjector in hand. The study period consisted of the 18 months before pathway revision (baseline) and the 18 months after revision.

RESULTS:

The overall admission rate decreased from 58.2% (106 of 182) in the baseline period to 25.3% (65 of 257) after pathway revision (P < .0001). There was no significant difference in the percentage of patients returning to the ED within 72 hours, and there were no adverse outcomes or deaths throughout the study period. After pathway revision, the median time to first epinephrine administration for the most critical patients was 10 minutes, and 85.4% (164 of 192) of patients were discharged with an epinephrine autoinjector in hand.

CONCLUSIONS:

By revising an anaphylaxis clinical pathway, we were able to streamline the care of patients with anaphylaxis presenting to a busy pediatric ED, without any compromise in safety. Most notably, decreasing the recommended length of observation from 8 to 4 hours resulted in a near 60% reduction in the average rate of admission.
Swimming exercise demonstrates advantages over running exercise in reducing proteinuria and glomerulosclerosis in spontaneously hypertensive rats
Authors: Totou NL , Moura SS , Coelho DB , Oliveira EC , Becker LK , Lima WG
Published: March 2018

Experimental studies in animal models have described the benefits of physical exercise (PE) to kidney diseases associated with hypertension. Land- and water-based exercises induce different responses in renal function. Our aim was to evaluate the renal alterations induced by different environments of PE in spontaneously hypertensive rats (SHRs). The SHRs were divided into sedentary (S), swimming exercise (SE), and running exercise (RE) groups, and were trained for 8 weeks under similar intensities (60 min/day). Arterial pressure (AP) and heart rate (HR) were recorded. The renal function was evaluated through urinary volume at each week of training; sodium and potassium excretions, plasma and urinary osmolarities, glomerular filtration rate (GFR), levels of proteinuria, and renal damage were determined. SE and RE rats presented reduced mean AP, systolic blood pressure, and HR in comparison with S group. SE and RE rats showed higher urine osmolarity compared with S. SE rats showed higher free water clearance (P < 0.01), lower urinary density (P < 0.0001), and increased weekly urine volume (P < 0.05) in comparison with RE and S groups. GFR was increased in both SE and RE rats. The proteinuria of SE (7.0 ± 0.8 mg/24 h) rats was decreased at the 8th week of the PE in comparison with RE (9.6 ± 0.8 mg/24 h) and S (9.8 ± 0.5 mg/24 h) groups. The glomerulosclerosis was reduced in SE rats (P < 0.02). SE produced different response in renal function in comparison with RE, in which only swimming-trained rats had better profile for proteinuria and glomerulosclerosis.
PERSPECTIVE TRANSPORT-POWER SYSTEM BASED ON THE INTEGRATION OF MAGLEV-TECHNOLOGY AND DISTRIBUTED PHOTO-ELECTRIC STATION
Authors: V. O. Dzenzerskiy  , A. B. Gnilenko  , S. V. Plaksin  , L. M. Pogorelaya  , Y. V. Shkil
Published: April 2018

Purpose. The research main purpose is the perfection of magnetolevitating technology on electrodynamic suspension and providing its functioning on the base of ecologically rational energy systems. It means creation of the MAGLEV transport-power system which uses renewable energy sources (in particular, photoelectric converters) and is connected to national/local networks as an energy user and producer simultaneously. Methodology. Conducted research, analysis and summary conclusions are based both on the results of works on the given subject, and own works of authors. The methods of systems analysis and computer design of components of the large cyber-physical transport-power system were used during research conducting. Findings. The physical-technical foundations of conception of the perspective transport-power system, which includes high-speed ground vehicle on electrodynamic suspension and distributed photo-electric energy complex are developed. The adapt to the performance of the given transport type and guaranteeing its safe functioning in any weather terms. Originality. For the first time authors substantiated the possibility for creation of single transport complex uniting the speed magnetolevitating system and distributed power supply system on the base of sun energy. It is simultaneously the inalienable part of the precision fast-acting control system, working in the real-time mode. Practical value. The offered scientific-technical solution allows on the base of renewable energy source to solve the problems of power supply and a high-speed transport control. Due to the inclusion of the distributed power supply system into local intellectual networks on the SMART-grid technology it gives the possibility to optimize energy consumption of territories neighboring to high-speed way.
Polish FDI in Central Asian Countries
Authors:   Gdańsk University of Technology (Poland), Gomółka Krystyna
Published: March 2018

Since gaining independence, Kazakhstan, Kyrgyzstan, Tajikistan, Turkmenistan and Uzbekistan gradually opened their markets to foreign investors. Before Poland’s accession to the European Union, the activities of Polish investors in Kazakhstan, Kyrgyzstan, Tajikistan, Turkmenistan and Uzbekistan were based on bilateral treaties concluded by Poland with those countries. Later, except Turkmenistan, they were governed by the partnership and cooperation agreements between the European Communities and their Member States. Despite the ample investment opportunities and favourable conditions for access to the market, the activity of Polish companies in these markets has not produced a significant effect. Poland invested with more considerable success on the markets in Kazakhstan and Kyrgyzstan. It made investment attempts in Tajikistan and Uzbekistan, leaving out Turkmenistan. The reason why Poland has a weak position in these markets is the distance between the partners and inability of Polish companies to effectively compete with large multinational companies which have been operating there for years. In the Kazakh market, good investment prospects are available for waste management, petrochemical, mining and road construction companies. In Kyrgyzstan, there are cooperation possibilities in the area of modern agricultural and processing technologies and establishment of fruit and vegetable processing enterprises. In Tajikistan, enterprises can invest in petroleum and natural gas extraction and exploitation, the fuel market, processing of precious metals and construction of conventional and hydroelectric power plants. In Turkmenistan, Polish companies can compete for road, railway and housing construction contracts, whereas in Uzbekistan they can invest in businesses covered by government tax reductions.
The Role of Trauma in Romania’s Ontological Security
Authors:   Vasile Goldis Western University in Arad (Romania), C. Salajan Loretta
Published: March 2018

This paper analyses Romania’s foreign policy during the first post-communist years, by employing a theoretical viewpoint based on ontological security and trauma. It uncovers the elite efforts to secure the post-totalitarian state’s identity and international course. Romania’s search for ontological security featured the articulation of narratives of victimhood, which were linked with its proclaimed western European identity. The Romanian identity narrative has long struggled between “the West” and “the East”, trying to cope with traumatic historical events. These discursive themes and ontological insecurities were crystallized in the controversy surrounding the Romanian-Soviet “Friendship Treaty” (1991). Key Romanian officials displayed different typical responses to cultural trauma and debated the state’s path to ontological security, which was reflected in the foreign policy positions.
THE ACCOUNTING OF INHOMOGENEITY THE UPPER PART IN THE PROCESSING OF SEISMIC DATA
Authors: Nanishvili Olga Alexandrovna
Published: April 2018

Researching of the upper part of profile is necessary to improve accuracy of seismic works. The article describe method of accounting static anomalies connected with the influence of the the upper part of the profile.
ANALYSIS OF INFORMAL INSTITUTIONS AFFECTING THE DEVELOPMENT OF BRANCHES OF THE ECONOMY OF THE NORTH RESOURCE-BREACHING REGION (ON THE EXAMPLE OF THE KHANTY-MANSIYSK AUTONOMOUS OKRUG - UGRA)
Authors: Bolshanik Petr Vladimirovich , Yevlanov Yevgeny Anatolevich , Islamutdinov Vadim Faruarovich , Islamutdinova Dina Faizrakhmanovna , Kovalev Vladimir Zakharovich , Rybina Vladlena Borisovna , Sannikov Dmitry Vasilievich , Tatyankin Vitaly Mikhailovich , Tei Dmitry Olegovich , Ustyugantseva Anastasia Nikolaevna , Shubina Victoria Igorevna
Published: April 2018

The subject of the study are informal institutions that influence the development of the Khanty-Mansiysk Autonomous Okrug - Ugra. The aim of the study is to identify the composition of informal institutions and the direction of their influence. The scientific significance of the work is to use an institutional approach to study the economy of the northern resource-producing region. The practical importance of the work lies in the possibility of the executive bodies of the state power applying the management of the region's branches to draw conclusions about the degree of influence of informal institutions on the development of the industry. The objectives of the study are: - studying the respondents' opinion on the impact of informal institutions; - study of the composition of informal institutions; - study of the direction of their influence. The research methodology includes comparative institutional analysis, questionnaires. The result of the work is an institutional analysis of the composition of informal institutions and their impact on the development of the economy of Khanty-Mansiysk Autonomous Okrug - Ugra.
FORECAST OF REVENUES FROM THE TAX ON EXTRACTION OF MINERALS FROM OIL PRODUCTION IN NEW DEPOSITS IN THE NORTHERN TERRITORIES
Authors: Razdrokov Evgeny Nikolaevich , Korosteleva Victoria Victorovna
Published: April 2018

The purpose of the research, the results of which are given in this article, is to compile a forecast of revenues to the budget system of the mineral extraction tax on new fields in Eastern Siberia and the Far East. To achieve this goal, we analyzed the factors associated with the change in the price of oil, the exchange rate of foreign currency, the volume of oil production in the investigated territories; with the loss of budget revenues from the exemption of mineral extraction tax and export duties. The subject of the study are the factors influencing the revenues to the budget system of the tax on the extraction of minerals. The scientific significance of the work lies in a comprehensive study of the influence of factors on the volume of tax revenues on the extraction of minerals in new fields in Eastern Siberia and the Far East. The practical importance of the work lies in the application of research results in decision-making in the field of taxation of mining operations. The objectives of the study are: - definition of the list of factors influencing the volume of revenues from the tax on the extraction of minerals in new deposits; - Establishment of the degree of influence of factors on the amount of revenues to the budget of the tax on the extraction of minerals; - forecasting the further development of the exchange rate of foreign currency, the volume of production, the drop-out income from the budget. In the process of work, the following research methods were used: statistical, computational, graphical, expert assessments, scenarios, etc. The result of the work is the identification of factors of revenues from the tax on extraction of minerals from oil production and their subsequent accounting in the process of forecasting the volume of tax revenue new deposits of Eastern Siberia and the Far East.
Index-based triangulation method for efficient generation of large three-dimensional ultrasonic C-scans
Authors: Mineo C , Riise J , Summan R , MacLeod C N , Pierce S G
Published: April 2018

The demand for high-speed ultrasonic scanning of large and complex components is driven by a desire to reduce production bottlenecks during the non-destructive evaluation (NDE) of critical parts. Emerging systems (including robotic inspection) allow for the collection of large volumes
of data in short time spans, compared to existing inspection systems. To maximise throughput, it is crucial that the reconstructed inspection datasets are generated and evaluated rapidly without loss of detail. This requires new data visualisation and analysis tools capable of mapping complex
geometries while guaranteeing full coverage. This paper presents an entirely new approach for the visualisation of three-dimensional (3D) ultrasonic C-scans, suitable for application to high data throughput ultrasonic phased array inspection of large and complex parts. Existing reconstruction
approaches are discussed and compared with the new index-based triangulation (IBT) method presented. The IBT method produces 3D C-scan representation, presented as coloured tessellated surfaces, and the approach is shown to work efficiently, even on challenging geometries. An additional differentiating
characteristic of the IBT method is that it allows for easy detection of lack of coverage (an essential feature for ensuring that inspection coverage can be guaranteed on critical components). The results demonstrate that the IBT C-scan generation approach runs over 60 times faster than a
C-scan display based on Delaunay triangulation and over 500 times faster than surface reconstruction C-scans. In summary, the main benefits of the new IBT technique include: high-speed generation of C-scans on large ultrasonic datasets (orders of magnitude improvement compared to surface reconstruction
C-scans); the ability to operate efficiently on 3D mapped datasets (allowing 3D interpretation of C-scans on complex geometry components); and intrinsic indication of lack of inspection coverage.
Drug utilization study in outpatient ophthalmology department of government medical college, Nellore, India
Authors: Gorantla Naveen Choudary , Hanumanthu Lalitha
Published: April 2018

Background: Drug utilization studies are an important part of rational use of drugs. This study was planned to assess drug utilization pattern in Ophthalmology outpatient department.Methods: After approval from Ethics Committee, 620 prescriptions were analyzed according to WHO drug indicators.Results: 2. 4 drugs were prescribed on an average per prescription. Antibiotics (49%) were the most commonly used drugs. Fluoroquinolones (54%) were frequently used. Topical route was preferred route of drug administration. Prescription of generic drugs was not optimal (13%). Duration of therapy was missing in many prescriptions.Conclusions: Generic prescribing can be improved. Duration of therapy should be mentioned in all prescriptions.
Cardiovascular risk factors and their association with carotid intima media thickness in children in Western India
Authors: Jain Ashish Kumar , Dani Sameer , Jain Parul
Published: April 2018

Background: Cardiovascular disease occurs in early in Indians risk factors of which may start from childhood. Objective was to identify CV risk factors in children and study their association with carotid intima media thickness.Methods: In this cross-sectional study, we studied children aged 4 to 14 years visiting our institute for routine health check-up. Data was collected on demographics, clinical and biochemical parameters. All patient underwent electrocardiographic, 2-D echocardiography examination. Carotid intima media thickness (CMT) was observed by carotid ultrasound.Results: In 378 children enrolled in the study, mean age was 9.1±2.6 years with 74.6% being males. Mean body mass index was 18.7±3.9 kg/m2. Among various CV risk factors, dyslipidemia (46.6%) was most common followed by family history of premature CV disease (9.5%), hypertension (4.49%), obesity (3.17%), smoking (1.05%). High dietary fat intake was seen in 22.2% cases. CMT showed significant association with age (p=0.027), BMI (p=0.031), systolic (p=0.026) and diastolic (p=0.036) blood pressure, high-density lipoprotein cholesterol levels (p=0.001), and low-density lipoprotein cholesterol (p=0.047). No association with fat intake or total calorie intake was observed.Conclusions: Dyslipidemia along other risk factors can be present as CV risk factor from early childhood. Screening of children for such risk factors to mitigate the risk of atherosclerotic CV disease in adulthood.