bluuebunny/crossref_metadata_2025 huggingface dataset:
Membrane Mechanisms Underlying Contrast Adaptation in Cat Area 17In Vivo
Authors: Sanchez-Vives Maria V. , Nowak Lionel G. , McCormick David A.
Published: April 2018

Contrast adaptation is a psychophysical phenomenon, the neuronal bases of which reside largely in the primary visual cortex. The cellular mechanisms of contrast adaptation were investigated in the cat primary visual cortexin vivothrough intracellular recording and current injections. Visual cortex cells, and to a much less extent, dorsal lateral geniculate nucleus (dLGN) neurons, exhibited a reduction in firing rate during prolonged presentations of a high-contrast visual stimulus, a process we termed high-contrast adaptation. In a majority of cortical and dLGN cells, the period of adaptation to high contrast was followed by a prolonged (5–80 sec) period of reduced responsiveness to a low-contrast stimulus (postadaptation suppression), an effect that was associated, and positively correlated, with a hyperpolarization of the membrane potential and an increase in apparent membrane conductance. In simple cells, the period of postadaptation suppression was not consistently associated with a decrease in the grating modulated component of the evoked synaptic barrages (the F1 component).

The generation of the hyperpolarization appears to be at least partially intrinsic to the recorded cells, because the induction of neuronal activity with the intracellular injection of current resulted in both a hyperpolarization of the membrane potential and a decrease in the spike response to either current injections or visual stimuli. Conversely, high-contrast visual stimulation could suppress the response to low-intensity sinusoidal current injection.

We conclude that control of the membrane potential by intrinsic neuronal mechanisms contributes importantly to the adaptation of neuronal responsiveness to varying levels of contrast. This feedback mechanism, internal to cortical neurons, provides them with the ability to continually adjust their responsiveness as a function of their history of synaptic and action potential activity.
Inhibition of Caspase-1-Like Activity by Ac-Tyr-Val-Ala-Asp-Chloromethyl Ketone Induces Long-Lasting Neuroprotection in Cerebral Ischemia through Apoptosis Reduction and Decrease of Proinflammatory Cytokines
Authors: Rabuffetti M. , Sciorati C. , Tarozzo G. , Clementi E. , Manfredi A. A. , Beltramo M.
Published: April 2018

Broad spectrum caspase inhibitors have been found to reduce neurodegeneration caused by cerebral ischemia. We studied whether blockade of group I caspases, mainly caspase-1, using the inhibitor Ac-YVAD.cmk reduced infarct volume and produced prolonged neuroprotection. Ac-YVAD.cmk (300 ng/rat) was injected intracerebroventricularly 10 min after permanent middle cerebral artery occlusion in the rat. Drug treatment induced a significant reduction of infarct volume not only 24 hr after ischemia (total damage, percentage of hemisphere volume: control, 41.1 ± 2.3%; treated, 26.5 ± 2.1%;p< 0.05) but also 6 d later (total damage: control, 30.6 ± 2.2%; treated, 23.0 ± 2.2%;p< 0.05). Ac-YVAD.cmk treatment resulted in a reduction not only of caspase-1 (control, 100 ± 20.3%; treated, 3.4 ± 10.4%;p< 0.01) but also of caspase-3 (control, 100 ± 30.3%; treated, 13.2 ± 9.5%;p< 0.05) activity at 24 hr and led to a parallel decrease of apoptosis as measured by nucleosome quantitation (control, 100 ± 11.8%; treated, 47 ± 5.9%;p< 0.05). Six days after treatment no differences in these parameters could be detected between control and treated animals. Likewise, brain levels of the proinflammatory cytokines IL-1β and TNF-α were reduced at 24 hr (39.5 ± 23.7 and 51.9 ± 10.3% of control, respectively) but not at 6 d. Other cytokines, IL-10, MCP-1, MIP-2, and the gaseous mediator nitric oxide, were not modified by the treatment. These findings indicate that blockade of caspase-1-like activity induces a long-lasting neuroprotective effect that, in our experimental conditions, takes place in the early stages of damage progression. Finally, this effect is achieved by interfering with both apoptotic and inflammatory mechanisms.
Functional Architecture of Synapses in the Inner Retina: Segregation of Visual Signals by Stratification of Bipolar Cell Axon Terminals
Authors: Wu Samuel M. , Gao Fan , Maple Bruce R.
Published: April 2018

We correlated the morphology of salamander bipolar cells with characteristics of their light responses, recorded under voltage-clamp conditions. Twelve types of bipolar cells were identified, each displaying a unique morphology and level(s) of axon terminal stratification in the inner plexiform layer (IPL) and exhibiting light responses that differed with respect to polarity, kinetics, the relative strengths of rod and cone inputs, and characteristics of spontaneous EPSCs (sEPSCs) and IPSCs. In addition to the well known segregation of visual information into ON and OFF channels along the depth of the IPL, we found an overlying mapping of spectral information in this same dimension, with cone signals being transmitted predominantly to the central IPL and rod signals being sent predominantly to the margins of the IPL. The kinetics of bipolar cell responses correlated with this segregation of ON and OFF and of rod and cone information in the IPL. At light offset, rod-dominated cells displayed larger slow cationic current tails and smaller rapid overshoot responses than did cone-dominated cells. sEPSCs were generally absent in depolarizing bipolar cells but present in all hyperpolarizing bipolar cells (HBCs) and larger in rod-dominated HBCs than in cone-dominated HBCs. Inhibitory chloride currents, elicited both at light onset and light offset, tended to be larger for cone-dominated cells than for rod-dominated cells. This orderly segregation of visual signals along the depth of the IPL simplifies the integration of visual information in the retina, and it begins a chain of parallel processing in the visual system.
Lens Injury Stimulates Axon Regeneration in the Mature Rat Optic Nerve
Authors: Leon Steven , Yin Yuqin , Nguyen Jennifer , Irwin Nina , Benowitz Larry I.
Published: April 2018

In mature mammals, retinal ganglion cells (RGCs) are unable to regenerate their axons after optic nerve injury, and they soon undergo apoptotic cell death. However, a small puncture wound to the lens enhances RGC survival and enables these cells to regenerate their axons into the normally inhibitory environment of the optic nerve. Even when the optic nerve is intact, lens injury stimulates macrophage infiltration into the eye, Müller cell activation, and increased GAP-43 expression in ganglion cells across the entire retina. In contrast, axotomy, either alone or combined with intraocular injections that do not infringe on the lens, causes only a minimal change in GAP-43 expression in RGCs and a minimal activation of the other cell types. Combining nerve injury with lens puncture leads to an eightfold increase in RGC survival and a 100-fold increase in the number of axons regenerating beyond the crush site. Macrophage activation appears to play a key role, because intraocular injections of Zymosan, a yeast cell wall preparation, stimulated monocytes in the absence of lens injury and induced RGCs to regenerate their axons into the distal optic nerve.
Chronic Hypersensitivity For Inflammatory Nociceptor Sensitization Mediated by the ε Isozyme of Protein Kinase C
Authors: Aley K. O. , Messing Robert O. , Mochly-Rosen Daria , Levine Jon D.
Published: April 2018

We have identified a mechanism, mediated by the ε isozyme of protein kinase C (PKCε) in peripheral neurons, which may have a role in chronic inflammatory pain. Acute inflammation, produced by carrageenan injection in the rat hindpaw, produced mechanical hyperalgesia that resolved by 72 hr. However, for up to 3 weeks after carrageenan, injection of the inflammatory mediators prostaglandin E2or 5-hydroxytryptamine or of an adenosine A2agonist into the same site induced a markedly prolonged hyperalgesia (>24 hr compared with 5 hr or less in control rats not pretreated with carrageenan). A nonselective inhibitor of several PKC isozymes and a selective PKCε inhibitor antagonized this prolonged hyperalgesic response equally. Acute carrageenan hyperalgesia could be inhibited by PKA or PKG antagonists. However, these antagonists did not inhibit development of the hypersensitivity to inflammatory mediators. Our findings indicate that different second messenger pathways underlie acute and prolonged inflammatory pain.
Social Status Controls Somatostatin Neuron Size and Growth
Authors: Hofmann Hans A. , Fernald Russell D.
Published: April 2018

Many animal species show flexible behavioral responses to environmental and social changes. Such responses typically require changes in the neural substrate responsible for particular behavioral states. We have shown previously in the African cichlid fish,Haplochromis burtoni, that changes in social status, including events such as losing or winning a territorial encounter, result in changes in somatic growth rate. Here we demonstrate for the first time that changes in social status cause changes in the size of neurons involved in the control of growth. Specifically, somatostatin-containing neurons in the hypothalamus ofH. burtoniincrease up to threefold in volume in dominant and socially descending animals compared with cell sizes in subordinate and socially ascending fish. Because somatostatin is known to be an inhibitor of growth hormone release, the differences in cell size suggest a possible mechanism to account for the more rapid growth rates of subordinate and socially ascending animals compared with those of dominant or socially descending fish. These results reveal possible mechanisms responsible for socially induced physiological plasticity that allow animals to shift resources from reproduction to growth or vice versa depending on the social context.
Rectification and Rapid Activation at Low Ca2+of Ca2+-Activated, Voltage-Dependent BK Currents: Consequences of Rapid Inactivation by a Novel β Subunit
Authors: Xia Xiao-Ming , Ding Jiu-Ping , Zeng Xu-Hui , Duan Kai-Lai , Lingle Christopher J.
Published: April 2018

A family of accessory β subunits significantly contributes to the functional diversity of large-conductance, Ca2+- and voltage-dependent potassium (BK) channels in native cells. Here we describe the functional properties of one variant of the β subunit family, which confers properties on BK channels totally unlike any that have as yet been observed. Coexpression of this subunit (termed β3) withSloα subunits results in rectifying outward currents and, at more positive potentials, rapidly inactivating (∼1 msec) currents. The underlying rapid inactivation process results in an increase in the apparent activation rate of macroscopic currents, which is coupled with a shift in the activation range of the currents at low Ca2+. As a consequence, the currents exhibit more rapid activation at low Ca2+relative to any other BK channel subunit combinations that have been examined. In part because of the rapid inactivation process, single channel openings are exceedingly brief. Although variance analysis suggests a conductance in excess of 160 pS, fully resolved single channel openings are not observed. The inactivation process results from a cytosolic N-terminal domain of the β3 subunit, whereas an extended C-terminal domain does not participate in the inactivation process. Thus, the β3 subunit appears to use a rapid inactivation mechanism to produce a current with a relatively rapid apparent activation time course at low Ca2+. The β3 subunit is a compelling example of how the β subunit family can finely tune the gating properties of Ca2+- and voltage-dependent BK channels.
Role of p38 Mitogen-Activated Protein Kinase in Axotomy-Induced Apoptosis of Rat Retinal Ganglion Cells
Authors: Kikuchi Masashi , Tenneti Lalitha , Lipton Stuart A.
Published: April 2018

p38 is a member of the mitogen-activated protein (MAP) kinase superfamily and mediates intracellular signal transduction. Recent studies suggest that p38 is involved in apoptotic signaling in several cell types, including neurons. In the mammalian retina, ∼50% of the retinal ganglion cells (RGCs) die by apoptosis during development. Additionally, transection of the optic nerve close to the eye bulb causes apoptotic cell death of RGCs in adulthood. We investigated the role of p38 in axotomy-induced apoptosis of RGCs. One day after axotomy, activated (phosphorylated) p38 was visualized by immunocytochemistry in the nuclei of RGCs, but not in control retinas. Phosphorylated p38 was first detected on immunoblots 12 hr after axotomy, reached a maximum at 1 d, and then decreased. To investigate possible roles of p38 in RGC death, a p38 MAP kinase inhibitor, SB203580, was administered intravitreally at the time of axotomy and repeated at 5 and 10 d. Assayed 14 d after axotomy, SB203580 increased the number of surviving RGCs in a dose-dependent manner (the minimum effective concentration was 1.6 μm). Furthermore, MK801, a selective inhibitor of NMDA receptors, not only showed protective effects against RGC apoptosis but also attenuated p38 MAP kinase activation in a dose-dependent manner. Our findings imply that p38 is in the signaling pathway to RGC apoptosis mediated by glutamate neurotoxicity through NMDA receptors after damage to the optic nerve. p38 inhibitors could be potentially useful for the treatment of optic nerve trauma and neurodegenerative diseases that affect RGCs, such as glaucoma.
Nerve Growth Factor-Induced Differentiation Changes the Cellular Organization of Regulated Peptide Release by PC12 Cells
Authors: Ng Yuen-Keng , Lu Xinghua , Watkins Simon C. , Ellis-Davies Graham C. R. , Levitan Edwin S.
Published: April 2018

PC12 cells, like endocrine chromaffin cells, undergo neuronal-like differentiation in response to nerve growth factor (NGF). Here we report that this phenotype conversion produces major changes in release of a green fluorescent protein-tagged neuropeptide–hormone. First, the spatial distribution of the releasable pool is altered; peptide release from untreated cells is supported predominantly by membrane-proximal vesicles, whereas a diffuse pool at the ends of processes is used by NGF-treated cells. Second, the time course of release evoked by photolysis of caged Ca2+is faster after differentiation. High-resolution measurements suggest that a slow step before membrane fusion dominates the kinetics of release in untreated cells. Finally, the effect of actin microfilament depolymerization on total release is altered by NGF treatment. This implies that the mechanism that limits the size of the releasable pool is altered by phenotype conversion. Therefore, the cellular organization of peptide release is plastic and changes in response to NGF. This flexibility may be used to generate cell-specific release properties.
Influence of Mild Hypothermia on Inducible Nitric Oxide Synthase Expression and Reactive Nitrogen Production in Experimental Stroke and Inflammation
Authors: Han Hyung Soo , Qiao Yanli , Karabiyikoglu Murat , Giffard Rona G. , Yenari Midori A.
Published: April 2018

Mild hypothermia is neuroprotective, but the reasons are not well known. Inflammation contributes to ischemic damage; therefore, we examined whether the protection by hypothermia may be attributable to alterations in the inflammation. We examined whether hypothermia might alter the inflammatory cell-associated inducible nitric oxide synthase (iNOS) and subsequent nitric oxide (NO) and peroxynitrite generation in experimental stroke and inflammation. Rats underwent 2 hr of middle cerebral artery occlusion (MCAO). Brain inflammation was modeled by intravenous lipopolysaccharide (LPS) (2 mg/kg) injection. Temperature was maintained at 33°C for 2 hr immediately after MCAO and LPS injection, delayed 2 hr after MCAO or maintained at 38°C. Cultured microglia were activated with LPS and then incubated at 33 or 37°C. Both intraischemic and delayed mild hypothermia attenuated infarct size by 40% (p< 0.05). Immunohistochemistry was performed to identify cell type, iNOS, and peroxynitrite. The majority of iNOS- and peroxynitrite-positive cells were activated microglia–macrophages, and mild hypothermia significantly decreased the numbers of immunoreactive cells at 72 hr by >50% (p< 0.05). After ischemia, mild hypothermia decreased NO production by 40%. Similarly, hypothermia attenuated NO and iNOS in LPS-injected rats, as well as in cultured microglia. Aminoguanidine, an iNOS inhibitor, also attenuated infarct size and NO in ischemic and inflammation models. We conclude that mild hypothermia significantly inhibits the inflammatory response by affecting microglial iNOS–NO generation. Therapies directed against microglia or their activation may be useful in treating stroke.
Inducible Nitric Oxide Synthase Mediates Retinal Apoptosis in Ischemic Proliferative Retinopathy
Authors: Sennlaub Florian , Courtois Yves , Goureau Olivier
Published: April 2018

Ischemic proliferative retinopathy (e.g., diabetes mellitus, retinopathy of prematurity, or retinal vein occlusion) is a major cause of blindness worldwide. Apart from neovascularization, ischemic proliferative retinopathy leads to retinal degeneration. Apoptosis has been ascribed to be the leading mechanism in ischemic retinal degeneration. We showed recently that inducible nitric oxide synthase (iNOS) is expressed in the avascular retina in proliferative retinopathyin vivoand that iNOS expression in retinal glial cells is responsible for retinal neuronal cell deathin vitro. Here we show that retinal apoptosis and subsequent degeneration occur in the murine model of ischemic proliferative retinopathy. Furthermore, because NO can have beneficial or detrimental effects in the retina, we analyzed the role of iNOS on retinal apoptosis in ischemic proliferative retinopathy. Using iNOS knock-out mice and iNOS inhibitor 1400W, we demonstratein vivothat iNOS expression induces apoptosis locally in the inner nuclear layer of the avascular retina and that protein nitration may be involved in this process.

These findings are the first evidence for retinal apoptosis in an animal model of ischemic proliferative retinopathy, demonstrating that iNOS plays a crucial role not only in retinal neovascular disease but also in retinal degeneration. We show that it is an ideal target to protect the hypoxic retina from degeneration and to improve its vascularization.
Localized Neuronal Outgrowth Induced by Long-Term Sensitization Training inAplysia
Authors: Wainwright Marcy L. , Zhang Han , Byrne John H. , Cleary Leonard J.
Published: April 2018

Biophysical, biochemical, and morphological studies have implicated sensory neurons as key sites of plasticity in the formation and retention of the memory of long-term sensitization inAplysia californica. This study examined the effects of different sensitization training protocols on the structure of sensory neurons mediating the tail-siphon withdrawal reflex. A 4 d training period produced a robust localized outgrowth in these sensory neurons observed 24 hr after the end of training. These changes are consistent with previous results in siphon sensory neurons (Bailey and Chen, 1988a). In contrast, 1 d of sensitization training, which has been shown to effectively induce long-term behavioral sensitization and synaptic facilitation (Frost et al., 1985; Cleary et al., 1998), is not associated with morphological changes in tail sensory neurons at either 24 hr or 4 d after training. Similarly, a single treatment with the growth factor TGF-β, which also induced facilitation, did not alter sensory neuron morphology. The different effectiveness of the two protocols was not simply a reflection of the number of stimuli presented, because a 1 d massed training protocol did not produce sensitization 24 hr after training, nor did it induce neuronal outgrowth.

These results suggest that extensive sensitization training is required to induce neuronal outgrowth in tail sensory neurons, indicating that the memory of long-term sensitization induced by 1 d of training is mechanistically different from that induced by 4 d of training. Moreover, the induction of a form of long-term sensitization associated with neuronal outgrowth does not appear to be a function of the amount of stimulation but does appear to be dependent on the temporal spacing of the stimulation over multiple days.
Elimination of the ρ1 Subunit Abolishes GABACReceptor Expression and Alters Visual Processing in the Mouse Retina
Authors: McCall Maureen A. , Lukasiewicz Peter D. , Gregg Ronald G. , Peachey Neal S.
Published: April 2018

Inhibition is crucial for normal function in the nervous system. In the CNS, inhibition is mediated primarily by the amino acid GABA via activation of two ionotropic GABA receptors, GABAAand GABAC. GABAAreceptor composition and function have been well characterized, whereas much less is known about native GABACreceptors. Differences in molecular composition, anatomical distributions, and physiological properties strongly suggest that GABAAreceptors and GABACreceptors have distinct functional roles in the CNS. To determine the functional role of GABACreceptors, we eliminated their expression in mice using a knock-out strategy. Although native rodent GABACreceptors are composed of ρ1 and ρ2 subunits, we show that after ρ1 subunit expression was selectively eliminated there was no GABACreceptor expression. We assessed GABACreceptor function in the retina because GABACreceptors are highly expressed on the axon terminals of rod bipolar cells and because this site modulates the visual signal to amacrine and ganglion cells. In GABACρ1 null mice, GABA-evoked responses, normally mediated by GABACreceptors, were eliminated, and signaling from rod bipolar cells to third order cells was altered. These data demonstrate that elimination of the GABACρ1 subunit, via gene targeting, results in the absence of GABACreceptors in the retina and selective alterations in normal visual processing.
Calcium Dynamics, Buffering, and Buffer Saturation in the Boutons of Dentate Granule-Cell Axons in the Hilus
Authors: Jackson Meyer B. , Redman Stephen J.
Published: April 2018

The axons of dentate gyrus granule cells form synapses in the hilus. Ca2+signaling was investigated in the boutons of these axons using confocal fluorescence imaging. Boutons were loaded with various concentrations of the Ca2+indicator Oregon Green BAPTA-1 by patch-clamping the cell bodies and allowing the dye to diffuse into the axon. Resting free [Ca2+] started at 74 nm, rose to ∼1 μmimmediately after an action potential, and then decayed to rest with a time constant of 43 msec (all extrapolated to a dye concentration of zero). Action potential-induced [Ca2+] rises were smaller in larger boutons, consistent with a size-independent Ca2+channel density of 45/μm2. Action potential-induced [Ca2+] changes varied with dye concentration in a manner consistent with κE∼20 for the ratio of endogenous buffer-bound Ca2+to free Ca2+. During trains of action potentials, [Ca2+] increments summed supralinearly by more than that expected from dye saturation. The amount of endogenous Ca2+buffering declined as [Ca2+] rose, and this saturation indicated a buffer with a dissociation constant of ∼500 nmand a concentration of ∼130 μm. This is similar to the dissociation constant of calbindin-D28K, a Ca2+-binding protein that is abundant in dentate granule cells. Thus, calbindin-D28K is a good candidate for the Ca2+buffer revealed by these experiments. The saturation of endogenous buffer can generate short-term facilitation by amplifying [Ca2+] changes during repetitive activity. Buffer saturation may also be relevant to the presynaptic induction of long-term potentiation at synapses formed by dentate granule cells.
Redistribution of Syntaxin mRNA in Neuronal Cell Bodies Regulates Protein Expression and Transport during Synapse Formation and Long-Term Synaptic Plasticity
Authors: Hu Jiang-Yuan , Meng Xu , Schacher Samuel
Published: April 2018

Syntaxin has an important role in regulating vesicle docking and fusion essential for neurotransmitter release. Here, we demonstrate that the distribution of syntaxin mRNA in cell bodies of sensory neurons (SNs) ofAplysiamaintained in cell culture is affected by synapse formation, synapse stabilization, and long-term facilitation (LTF) produced by 5-HT. The distribution of the mRNA in turn regulates expression and axonal transport of the protein. Syntaxin mRNA and protein accumulated at the axon hillock of SNs during the initial phase of synapse formation. Significant numbers of granules containing syntaxin were detected in the SN axon. When synaptic strength was stable, both mRNA and protein were targeted away from the axon hillock, and the number of syntaxin granules in the SN axon was reduced. Dramatic increases in mRNA and protein accumulation at the axon hillock and number of syntaxin granules in the SN axon were produced when cultures with stable connections were treated with 5-HT that evoked LTF. Anisomycin (protein synthesis inhibitor) or KT5720 (protein kinase A inhibitor) blocked LTF, accumulation of syntaxin mRNA and protein at the axon hillock, and the increase in syntaxin granules in SN axons. The results indicate that without significant effects on overall mRNA expression, both target interaction and 5-HT via activation of protein kinase A pathway regulate expression of syntaxin and its packaging for transport into axons by influencing the distribution of its mRNA in the SN cell body.
Calcitonin Gene-Related Peptide Regulates Expression of Neurokinin1Receptors by Rat Spinal Neurons
Authors: Seybold Virginia S. , McCarson Kenneth E. , Mermelstein Paul G. , Groth Rachel D. , Abrahams Lia G.
Published: April 2018

Although neurokinin 1 (NK1) receptors contribute to hyperalgesia, and their expression is increased in the spinal cord during peripheral inflammation, little is known regarding the signaling molecules and the second messenger pathways that they activate in regulating the expression of the NK1 receptor gene. Because the promoter region of the NK1 receptor contains a cAMP response element (CRE), we tested the hypothesis that calcitonin gene-related peptide (CGRP) regulates the expression of NK1 receptors via a pathway involving activation of the transcription factor cAMP response element binding protein (CREB). Experiments were conducted on primary cultures of neonatal rat spinal neurons. Treatment of cultures with CGRP for 8–24 hr increased125I-substance P binding on spinal neurons; the increase in binding was preceded by an elevation in NK1 receptor mRNA. The CGRP-induced change in125I-substance P binding was concentration-dependent and was inhibited by the antagonist CGRP8–37. CGRP increased phosphorylated CREB immunoreactivity and CRE-dependent transcription in neurons, indicating the involvement of the transcription factor CREB. Evidence that CGRP increased cAMP levels in spinal neurons and that the protein kinase A inhibitor H89 attenuated CGRP-induced CRE-dependent transcription suggests that the intracellular pathway stimulated by CGRP leads to activation of protein kinase A. Collectively these data define a role for CGRP as a signaling molecule that induces expression of NK1 receptors in spinal neurons. The data provide evidence that a neuropeptide receptor controls gene expression in the CNS and add another dimension to understanding the cotransmission of substance P and CGRP by primary afferent neurons.
Task-Dependent Presynaptic Inhibition
Authors: Côté Marie-Pascale , Gossard Jean-Pierre
Published: April 2018

This study compares the level of presynaptic inhibition during two rhythmic movements in the cat: locomotion and scratch. Dorsal rootlets from L6, L7, or S1 segments were cut, and their proximal stumps were recorded during fictive locomotion occurring spontaneously in decerebrate cats and during fictive scratch induced byd-tubocurarine applied on the C1 and C2 segments. Compared with rest, the number of antidromic spikes was increased (by 12%) during locomotion, whereas it was greatly decreased (31%) during scratch, and the amplitude of dorsal root potentials (DRPs), evoked by stimulating a muscle nerve, was slightly decreased (7%) during locomotion but much more so during scratch (53%). When compared with locomotion, the decrease in the number of antidromic spikes (45%) and the decrease in DRP amplitude (43%) during scratch were of similar magnitude. Also, the amplitude of primary afferent depolarization (PAD), recorded with micropipettes in axons (n= 13) of two cats, was found to be significantly reduced (60%) during scratch compared with rest. During both rhythms, there were cyclic oscillations in dorsal root potential the timing of which was linearly related to the timing of rhythmic activity in tibialis anterior. The amplitude of these oscillations was significantly smaller (34%) during locomotion compared with scratch. These results suggest that the reduction in antidromic activity during scratch was attributable to a task-dependent decrease in transmission in PAD pathways and not to underlying potential oscillations related to the central pattern generator. It is concluded that presynaptic inhibition and antidromic discharge may have a more important role in the control of locomotion than scratch.
Reversible Disorganization of the Locomotor Pattern after Neonatal Spinal Cord Transection in the Rat
Authors: Norreel Jean-Chrétien , Pflieger Jean-François , Pearlstein Edouard , Simeoni-Alias Juliette , Clarac François , Vinay Laurent
Published: April 2018

The central pattern generators (CPGs) for locomotion, located in the lumbar spinal cord, are functional at birth in the rat. Their maturation occurs during the last few days preceding birth, a period during which the first projections from the brainstem start to reach the lumbar enlargement of the spinal cord. The goal of the present study was to investigate the effect of suppressing inputs from supraspinal structures on the CPGs, shortly after their formation. The spinal cord was transected at the thoracic level at birth [postnatal day 0 (P0)]. We examined during the first postnatal week the capacity of the CPGs to produce rhythmic motor activity in two complementary experimental conditions. Left and right ankle extensor muscles were recordedin vivoduring airstepping, and lumbar ventral roots were recordedin vitroduring pharmacologically evoked fictive locomotion. Mechanical stimulation of the tail elicited long-lasting sequences of airstepping in the spinal neonates and only a few steps in sham-operated rats.In vitroexperiments made simultaneously on spinal and sham animals confirmed the increased excitability of the CPGs after spinalization. A left–right alternating locomotor pattern was observed at P1–P3. Both types of experiments showed that the pattern was disorganized at P6–P7, and that the left–right alternation was lost. Alternation was restored after the activation of serotonergic 5-HT2receptorsin vivo. These results suggest that descending pathways, in particular serotonergic projections, control the strength of reciprocal inhibition and therefore shape the locomotor pattern in the neonatal rat.
Glial Cell Line-Derived Neurotrophic Factor Increases Stimulus-Evoked Dopamine Release and Motor Speed in Aged Rhesus Monkeys
Authors: Grondin Richard , Cass Wayne A. , Zhang Zhiming , Stanford John A. , Gash Don M. , Gerhardt Greg A.
Published: April 2018

Changes in the functional dynamics of dopamine release and regulation in the basal ganglia have been posited to contribute to age-related slowing of motor functions. Here, we report the effects of glial cell line-derived neurotrophic factor (GDNF) on the stimulus-evoked release of dopamine and motor speed in aged monkeys (21–27 years of age;n= 10). Although no changes were observed in the vehicle controls (n= 5), chronic infusions of 7.5 μg of GDNF per day for 2 months into the right lateral ventricle initially increased hand movement speed up to 40% on an automated hand-reach task. These effects were maintained for at least 2 months after replacing GDNF with vehicle, and increased up to another 10% after the reinstatement of GDNF treatment for 1 month. In addition, upper-limb motor performance times of the aged GDNF-treated animals (n= 5) recorded at the end of the study were similar to those of five young adult monkeys (8–12 years of age). The stimulus-evoked release of dopamine was significantly increased, up to 130% in the right caudate nucleus and putamen and up to 116% in both the right and left substantia nigra of the aged GDNF recipients compared with vehicle controls. Also, basal extracellular levels of dopamine were bilaterally increased, up to 163% in the substantia nigra of the aged GDNF-treated animals. The data suggest that the effects of GDNF on the release of dopamine in the basal ganglia may be responsible for the improvements in motor functions and support the hypothesis that functional changes in dopamine release may contribute to motor dysfunctions characterizing senescence.
The European origins of the Israeli-Palestinian economic union: A genealogical approach
Authors: Levin Jamie
Published: April 2018

The Oslo peace process established a modified economic union between Israel and the Palestinian Authority. Economic unions require extensive collaboration and are generally found between states that enjoy pacific relations and are looking to deepen integration and political ties. The choice of an economic union between these adversaries is puzzling given that the aim of the peace process was to disentangle Israelis and Palestinians by establishing two separate states. Today, after the optimism surrounding the process has faded, it is easy to see the arrangement as a perpetuation of Israeli control over Palestinian life. However, such assessments fail to consider, first, the depth of the negotiations; second, the significant differences between the outcome of the negotiations and what was previously imposed by Israel; and, third, the gap between what was negotiated and what was later implemented. This article traces the genealogy of the economic union by exploring all three factors. While the negotiators did not start with a tabula rasa, they attempted to alter the existing economic arrangement along the European neo-functionalist model of integration. This approach was later largely abandoned, and what followed bore little resemblance to the positive spillover effects in Europe.
ІНТЕГРАЦІЙНІ МЕХАНІЗМИ РОЗВИТКУ УКРАЇНСЬКОГО РИНКУ ХЛІБА ТА ХЛІБОБУЛОЧНИХ ВИРОБІВ
Authors: Нікішина О. В. , Бібікова Н. О.
Published: April 2018

Визначено інтеграційні тенденції та проблеми розвитку вітчизняного ринку хліба та хлібобулоч-них виробів у розрізі офіційного та «тіньового» сегментів. Показано трансформаційний вплив «тіньово-го» сегменту на відтворювальний розвиток хлібного ринку України. Ідентифіковано тенденцію посиленняінтеграційних зв’язків між «тіньовими» сегментами суміжних ринків борошна та хліба. Обґрунтовано сут-ність та компоненти трьох ринкових інтеграційних механізмів, цілеспрямовано зорієнтованих на віднов-лення та зміцнення інтеграційних зв’язків між суб’єктами виробничого та сировинного й торгового секто-рів хлібного ринку. Акцентовано увагу на пасивному характері діючої інтеграційної політики держави, щопрактично не охоплює споживчий сектор продовольчих ринків. За результатами аналізу ідентифікованоціновий диспаритет у споживчому секторі хлібного ринку та обґрунтовано механізм його подолання, пок-ликаний збільшити кількість інтеграційних зв’язків між покупцями та виробниками якісного хліба легаль-ного сектору ринку.
АДАПТИВНІСТЬ ЯК КЛЮЧОВИЙ ФАКТОР КОНКУРЕНТОСПРОМОЖНОСТІ ПІДПРИЄМСТВА
Authors: Ліпова О. Л. , Черевата Т. М.
Published: April 2018

В статті розглянуто та обґрунтовано закономірний взаємозв’язок ринкових категорій «адапти-вність підприємства» та «конкурентоспроможність підприємства», досліджено прикладний аспект що-до етапів адаптаційного процесу підприємства.В статті визначено актуальність адаптаційного процесу підприємства як основи розвитку йогоконкурентоспроможності. Уточнено визначення категорії «адаптивність підприємства» як здатність,можливість та швидкість його реагування на зміни та виклики, що відбуваються як у зовнішньому се-редовищі, так і у внутрішніх умовах господарювання. Запропоновано рекомендації практичної адап-тації суб’єктів господарювання. Акцентовано увагу на різновидах стану адаптивності. Розробленопослідовність етапів адаптації в контексті турбулентної економіки.
FEATURES OF RISK ASSESSMENT OF INDUSTRIAL ENTERPRISES ACTIVITIES
Authors: Basіurkina N. , Shaleny V.
Published: April 2018

The article deals with the main theoretical aspects of risk assessment of industrial enterprises in theshort-and long-term periods. The main features of short-term and long-term risks inherent to industrial enterprises have been determined. Comprehensive risk assessment methodology has been developed based onobtaining coherent assessment of the level of short-term and long-term risks. This methodology can be implemented in the form of an express assessment (simplified risk assessment) and in the form of risk matrix(advanced assessment of risks), depending on the objectives of the assessment, available resources andother constraints. The expediency of using an express assessment is, first of all, in the analysis of dynamicsof the level of risk at the enterprise. By positioning the risk profile of an enterprise in a certain area of thematrix of risks, it is possible to determine the main reserves for reducing the overall level of risk and increasethe effectiveness of risk management. The assessment of the risk level dynamics of activity, obtained in theform of risk vector, also provides significant basis for decision making on risk management.
ФІНАНСОВА ПОЛІТИКА І БЮДЖЕТНА БЕЗПЕКА УКРАЇНИ
Authors: Тарасова О. В.
Published: April 2018

У статті досліджуються проблеми забезпечення бюджетної безпеки України, яка відіграє над-звичайно важливу роль у розвитку суспільства. Розглянуто зміст фінансової політики як частиниекономічної політики держави. Визначені методологічні принципи, на базі яких має здійснюватисяфінансова політика: орієнтованість на кінцеву мету; макроекономічна збалансованість усіх галузейекономіки; відповідність інтересам всіх членів суспільства; використання економічних законів; враху-вання внутрішніх і зовнішніх факторів впливу. Обґрунтовано роль фінансової політики у забезпеченністабільного економічного зростання. Визначені основні загрози бюджетній безпеці України: високийрівень державного боргу; значний дефіцит державного бюджету; підвищення частки видатків держав-ного бюджету на фінансування потреб оборони та безпеки; інфляційно-девальваційні коливання.Сформульовані завдання, вирішення яких дозволить оптимізувати фінансову політику.
Study of Chlorophyll-related Compounds from Dietary Spinach in Human Blood
Authors: CHAO Pi-Yu , HUANG Meng-Yuan , HUANG Wen-Dar , LIN Kuan-Hung Robert , CHEN Shiau-Ying , YANG Chi-Ming
Published: April 2018

Human bioavailability data on chlorophyll (Chl) is very limited. The distribution of Chl-related compounds (CRCs) derived from dietary spinach was investigated in human blood. Eight healthy adults, aged from 21 to 61 year-old, consumed 1.2 kg of just-boiled fresh spinach after an 8-h overnight fast. Before and then 3 h after consuming the spinach, blood samples were taken from each participant. Freeze-dried blood samples were prepared, and 80% acetone was added for grinding. Eight peaks were found in the blood using high-performance liquid chromatography (HPLC), and the main CRCs in the samples were pheophytin (Phe) and pheophorbide (Pho) derivates. Compared to a fasted state, markedly higher levels of blood CRCs were detected in all subjects, except that Pho metabolites were not found in two subjects. No significant differences were seen in most of the peaks between males and females; however, relatively higher CRCs levels were observed in females, particular of Pho derivates. In addition, the blood contained significantly higher levels of Phe in the 36~61-year-old group than in the 21~35-year-old group. These results suggest that the conversion of Chls to CRCs is a rapid process, and Chls obtained by ingestion can be absorbed by the human body.
Morphological and Physiological Germination Aspects of Anadenanthera colubrina (Vell.) Brenan
Authors: NERY Fernanda Carlota , NERY Marcela Carlota , PRUDENTE Débora de Oliveira , ALVARENGA Amauri Alves de , PAIVA Renato
Published: April 2018

Anadenanthera colubrina is a species native to Brazil, from the Fabaceae family and has potential for use in the timber industry, in the reforestation of degraded areas, besides having medicinal properties. Its propagation is mainly by seeds, but basic subsidies regarding the requirements for optimal germination conditions are still lacking. Aiming to contribute to the expansion of its cultivation, rational use and conservation, the objective of this study was to investigate the morphology and anatomy of fruits and seeds, as well as the responses to factors as thermal regimes and substrates in seed germination. The 1000-seed weight and seeds per fruit were determined. To characterize the seed tissues, histochemical test with Sudan III and Lugol was used. The temperatures analyzed in the germination test were 15-25 °C; 25 °C; 20-30 °C and 30 °C. Different substrates for germination (paper rolls, paper sheet such as “germitest”, commercial substrate and sand) were also analyzed in the presence of light at 30 °C. The average number of seeds per fruit is 10 and the 1000-seed weight is 118 g. Germination is fast and high over a wide temperature range; however, the temperature of 25 °C contributes to a substantial increase in the percentage of abnormal seedlings and dead seeds, both in the absence and presence of light. A. colubrina seeds are indifferent to light and the highest vigor was verified at 30 °C. Sand and commercial substrates are efficient in initial seedling development.
Identification of Nitric Oxide Responsive Genes in the Rudimentary Leaves of Litchi chinensis
Authors: LU Xingyu , CHEN Houbin , HU Zhiqun , ZHOU Biyan
Published: April 2018

Litchi (Litchi chinensis Sonn.) is an evergreen woody fruit tree widely cultivated in subtropical and tropical regions. Warm winter and hot spring often leads to abnormal floral differentiation in litchi. Under this condition, the rudimentary leaves in the floral buds expand and the inflorescences will stop developing. Thus, how to promote abortion of rudimentary leaves in litchi inflorescence are important for floral development. Previous study indicated that nitric oxide (NO) produced by sodium nitroprusside (SNP) promoted flowering and abortion of rudimentary leaves in litchi. In the present study, a suppression subtractive hybridization (SSH) was used to identify NO responsive genes. As a result, 16 high homologous ESTs were obtained from the SSH library of the SNP treated rudimentary leaves. The ESTs were classified into three groups. They are disease/defensive, protein destination and storage, and protein synthesis. Quantitative reverse transcription PCR (qRT-PCR) analysis indicated that 6 out of the 7 randomly selected ESTs’expression showed an increasing trend from 0 h to 10 h of SNP treatment. It is suggested that the litchi homologs 18S ribosomal RNA gene, cytochrome P450 like TBP, and the senescence-associated protein, chaperone protein, and a hypothetical protein encoding genes may be involved in the NO-induced senescence in litchi rudimentary leaves. LcERD15-like may be a key gene involved in this process.
Cucurbita maxima Pumpkin Seed Oil: from the Chemical Properties to the Different Extracting Techniques
Authors: REZIG Leila , CHOUAIBI Moncef , OJEDA-AMADOR Rosa Maria , GOMEZ-ALONSO Sergio , SALVADOR Maria Desamparados , FREGAPANE Giuseppe , HAMDI Salem
Published: April 2018

Pumpkin seed oils are rich in bioactive compounds such as tocopherols, sterols, β-carotene, and lutein that have, along with some fatty acids, high nutritional value factors. In addition, it has so far been proven that these compounds have a positive effect on human health. The present study mainly aimed at evaluating the chemical composition and the bioactive compounds of pumpkin (Cucurbita maxima) seed oil of the ‘Béjaoui’ Tunisian cultivar using both cold pressing and solvent extraction methods. The seed oils contained substantial amounts of unsaturated fatty acids, particularly oleic and linoleic acids, with values ranging respectively from 28.19% for cold pressed pumpkin seed oil to 30.56% for pumpkin seed oil extracted by pentane and from 43.86% for pumpkin seed oil extracted by pentane to 46.67% for cold pressed pumpkin seed oil of the total amount of fatty acids. Investigations of different seed oils revealed that extraction techniques had significant effects on the antioxidant activity and the γ-tocopherol. Cold pressed pumpkin seed oil revealed the highest γ-tocopherol content (599.33 mg kg-1) and the highest oxidative stability (3.84 h). However, the chloroform/methanol extracted pumpkin seed oil, which is rich in total phenolics (54.41 mg Gallic Acid Equivalent kg-1), was a more effective scavenger of DPPH radicals (250 µmoles Trolox kg-1) than the poor phenolic pumpkin seed oils extracted by hexane and pentane (110 µmoles Trolox kg-1 vs 100 µmoles Trolox kg-1). Based on its unique seed oil features, cold press extracted pumpkin seed may add great value to product innovation in the industrial, nutritional, cosmetic, and pharmaceutical fields.
Estimation of Mating System in the Endangered Aquatic Fern Ceratopteris pteridoides in China Based on AFLP Molecular Marker and Selfing Test: Implications for Conservation
Authors: DONG Xiang , LIU Hong , GAO Wei , QIN Rui , GICHIRA Andrew W. , WANG Mo , LIAO Kuo
Published: April 2018

Mating system has important implications for the genetic structure and diversity of populations, especially threatened and endangered species. In this study, mating system of the endangered aquatic fern Ceratopteris pteridoides in China was investigated using AFLP markers and selfing test. The results of AFLP analyses showed that the estimate of multilocus outcrossing rate (tm) was high at species level (tm = 0.999), indicating that C. pteridoides is a predominant outcrossing species. The small differences between tm and ts (0.136 ± 0.003) at species level showed that there is a low tendency for mating between relatives. The selfing test showed that isolated gametophytes formed the rate of normal sporophytes in three populations (BLH, ZDH, WCH) ranging from 72.9% to 77.8% with a mean value of 75.2%, indicating that C. pteridoides has a high level of intragametophytic selfing potential. Our investigation found that some of the studied populations of C. pteridoides have a prolific capacity for vegetative reproduction (clonal growth). The results revealed that the diploid homosporous pteridophyte C. pteridoides predominantly favors gametophytic crossing with a certain level of inbreeding along with clonal growth. We suggest that mating system of C. pteridoides may be adjusted to promote selfing rate in response to factors including the characteristics of hermaphrodite, and colonization events and small extant populations. As a result of the high outcrossing rate of C. pteridoides, we recommend that ex situ plantings would be most suitable for enhancing possible intermingling of the different populations thus minimizing inbreeding.