bluuebunny/crossref_metadata_2025 huggingface dataset:
Three-dimensional visualization of the smooth endoplasmic reticulum in Purkinje cell dendrites
Authors: Martone ME , Zhang Y , Simpliciano VM , Carragher BO , Ellisman MH
Published: March 2018

The three-dimensional organization of the smooth endoplasmic reticulum (SER) in Purkinje cell dendrites in the chick cerebellum was investigated to assess the connectivity between its various components. Three-dimensional reconstructions of the SER within portions of Purkinje cell dendrites were performed from serial sections through the cerebellar molecular layer. In addition, semithick and thick sections (0.25–1 micron) of chick cerebellum in which the endomembrane system had been selectively stained were examined with an intermediate high- voltage electron microscope. Three-dimensional information was extracted from thick sections using stereo pairs and tomographic reconstructions from single axis tilt series. In contrast to its discontinuous appearance in thin sections, in both the three- dimensional reconstructions and selectively stained thick sections the endoplasmic reticulum formed a highly interconnected network of tubules and cisterns extending throughout the dendritic shaft and into the spines. Several distinct morphological domains of endoplasmic reticulum were noted, including the hypolemmal cisternae, the endomembranes associated with the dendritic spines, and the tubular and cisternal endoplasmic reticulum in the dendritic shaft. In older chicks (aged 2 weeks), stacks of endoplasmic reticulum were also noted within the dendritic shaft. All elements of the SER within the dendritic shaft and spine appeared to be continuous with one another. The results of this study strongly suggest that the endoplasmic reticulum forms a complicated network that may be part of a single endomembrane system within Purkinje cell dendrite.
Optokinetically evoked expression of corticotropin-releasing factor in inferior olivary neurons of rabbits
Authors: Barmack NH , Errico P
Published: March 2018

We investigated the influence of both binocular and monocular optokinetic stimulation on the expression of corticotropin-releasing factor (CRF), a neuropeptide, in inferior olivary neurons. Rabbits were placed at the center of a cylindrical optokinetic drum that rotated at a constant velocity of 5 degrees/sec, stimulating one eye in the posterior-->anterior direction and the other eye in the anterior-- >posterior direction. After 48 hr of optokinetic stimulation, rabbits were killed and the brains were prepared for immunohistochemistry. An antiserum to rat/human CRF was used to label brain-stem sections of optokinetically stimulated rabbits. The density of CRF-specific reaction product within individual olivary neurons was analyzed with a computer-based densitometer. Binocular optokinetic stimulation for 48 hr caused a 20–70% increase in the optical density of “stimulated” dorsal cap neurons, measured relative to the optical density of control (“unstimulated”) olivary neurons in the same histological section. This elevated expression of CRF lasted approximately 48 hr. When a delay of 18 hr was interposed between optokinetic stimulation and death of the rabbit, during which the rabbits were deprived of pattern vision, then both dorsal caps were densely labeled. Monocular optokinetic stimulation for 48 hr in the anterior-->posterior direction caused no change in CRF expression in either dorsal cap if the rabbit was immediately killed. However, following monocular anterior-->posterior stimulation, the dorsal cap contralateral to the “null-stimulated” eye was densely labeled if the rabbit was deprived of pattern vision for 18 hr prior to death. We infer that stopping prolonged “null stimulation” causes a rebound in activity in the stimulated dorsal cap. This “rebound” must have its origin at the level of the dorsal cap or more peripherally in the optokinetic pathway.
A neurobiological model of visual attention and invariant pattern recognition based on dynamic routing of information
Authors: Olshausen BA , Anderson CH , Van Essen DC
Published: March 2018

We present a biologically plausible model of an attentional mechanism for forming position- and scale-invariant representations of objects in the visual world. The model relies on a set of control neurons to dynamically modify the synaptic strengths of intracortical connections so that information from a windowed region of primary visual cortex (V1) is selectively routed to higher cortical areas. Local spatial relationships (i.e., topography) within the attentional window are preserved as information is routed through the cortex. This enables attended objects to be represented in higher cortical areas within an object-centered reference frame that is position and scale invariant. We hypothesize that the pulvinar may provide the control signals for routing information through the cortex. The dynamics of the control neurons are governed by simple differential equations that could be realized by neurobiologically plausible circuits. In preattentive mode, the control neurons receive their input from a low-level “saliency map” representing potentially interesting regions of a scene. During the pattern recognition phase, control neurons are driven by the interaction between top-down (memory) and bottom-up (retinal input) sources. The model respects key neurophysiological, neuroanatomical, and psychophysical data relating to attention, and it makes a variety of experimentally testable predictions.
Ciliary neurotrophic factor maintains motoneurons and their target muscles in developing rats
Authors: Forger NG , Roberts SL , Wong V , Breedlove SM
Published: March 2018

Ciliary neutrophic factor (CNTF) can enhance motoneuron survival during naturally occurring cell death in the chick (Oppenheim et al, 1991). Because receptors for CNTF are expressed in both motoneurons and their target muscles (Davis et al., 1991; lp et al., 1993), both tissues are potential sites of CNTF action in development. We examined the ability of CNTF to prevent the degeneration of a neuromuscular system in developing female rats. The death of motoneurons in the spinal nucleus of the bulbocavernosus (SNB) extends postnatally and is sexually dimorphic, with many more motoneurons dying in females than in males. The bulbocavernosus (BC), a target muscle of SNB motoneurons, also degenerates postnatally in females. Female rats treated with daily injections of 1 microgram CNTF from embryonic day 22 through postnatal day 3 (P3) had 70% more SNB motoneurons on P4 than did control animals, and the number of pyknotic profiles in the SNB area was markedly reduced by CNTF. In addition, the degeneration of the BC was completely prevented by CNTF treatment of perinatal female rats. These results demonstrate that CNTF can preserve mammalian motoneurons from developmental death, but also suggest that the sparing effect of CNTF on motoneurons in vivo may be a secondary consequence of effects on target muscles.
Omega-conotoxin prevents myelin-evoked growth cone collapse in neonatal rat locus coeruleus neurons in vitro
Authors: Moorman SJ , Hume RI
Published: March 2018

The response of neonatal rat locus coeruleus neurons to contact with myelin extracts prepared from the CNS and PNS was examined. The growth cones of these neurons collapsed following contact with central myelin, but continued to elongate on contact with peripheral myelin. Central myelin elicited an increase in the intracellular free calcium concentration in these growth cones, while peripheral myelin did not. This increase appeared to require transmembrane calcium flux, since it was blocked by extracellular EGTA, and also by extracellular cobalt. These neurons express N- and L-type calcium channels. Exposure to 5 microM omega-conotoxin GVIA, a specific blocker of N-type channels, prevented both the myelin-evoked increase in growth cone calcium concentration and the collapse of growth cones.
Quantitative ultrastructure of Ia boutons in the ventral horn: scaling and positional relationships
Authors: Pierce JP , Mendell LM
Published: March 2018

Three physiologically characterized spindle (group Ia) afferents were labeled by the intracellular injection of HRP and were processed for light-level reconstruction. Thirty-five boutons in the ventral horn were then selected for analysis. They were serially thin sectioned and characterized in terms of volume, total surface area and the surface area of apposition to postsynaptic neurons (apposed surface area), mitochondrial volume, vesicle and active zone features, relation to presynaptic contacts, postsynaptic profile size, and position within the terminal arbor. Virtually all of these characteristics were widely variable, both within the entire population and in the endings of a single fiber. Apposed surface area, mitochondrial volume, vesicle number, active zone vesicle number, active zone number, and total active zone area were highly correlated in a positive linear manner with bouton volume. This suggests a type of ultrastructural “size principle,” in which the morphological features associated with synaptic release scale directly in proportion to bouton size. This pattern also extends to local circuit interactions: the extent of an Ia bouton's input from axoaxonal contacts (86% receive at least one axoaxonal contact) was directly proportional to its size. In addition, the characteristics of an Ia bouton were related to its position on the postsynaptic element and within the terminal arbor. Vesicle density, percentage mitochondrial volume, and active zone size increased as the postsynaptic process decreased in size, while volume, apposed surface area, active zone number and area, and vesicle number all decreased as one moved downstream within a terminal branch, with the exception of the terminal bouton. Vesicle density also decreased as one moved away from the dorsal root entry zone.
Several extracellular domains of the neural cell adhesion molecule L1 are involved in neurite outgrowth and cell body adhesion
Authors: Appel F , Holm J , Conscience JF , Schachner M
Published: March 2018

The neural cell adhesion molecule L1 is a multidomain protein that plays important roles in cell adhesion, migration, and neurite outgrowth. To analyze structure-function relationships of L1 in neurite outgrowth and cell body adhesion, we have expressed and purified a set of different fragments of the extracellular part of this glycoprotein in CHO cells and in Escherichia coli. When neurite outgrowth from small cerebellar neurons was measured on substrate-coated L1 or L1 fragments, neurite outgrowth was promoted by the immunoglobulin-like domains I-II, III-IV, and V-VI, and by the fibronectin type III homologous repeats 1– 2, while the fibronectin type III homologous repeats 3–5 were ineffective. In contrast, cell bodies of small cerebellar neurons adhered mostly to the immunoglobulin-like domains I-II and V-VI, and to the fibronectin type III homologous repeats 3–5, but less to the immunoglobulin-like domains III-IV and fibronectin type III homologous repeats 1–2. In both assays, the neuronal cell surface receptor for all active protein fragments was identified as L1. No significant differences in functional activities were found between fragments with and without carbohydrate structures. These findings indicate that L1 uses several domains for homophilic interactions overlapping for the two functions analyzed here, but also showing some regional specialization. Furthermore, we show that a homophilic molecule uses several domains in one function, with neurite outgrowth requiring more domains than adhesion for maximal activity.
Thresholds for synaptic activation of transcription factors in hippocampus: correlation with long-term enhancement
Authors: Worley PF , Bhat RV , Baraban JM , Erickson CA , McNaughton BL , Barnes CA
Published: March 2018

Recent studies suggest a role for rapid induction of transcription factors in stimulus-induced neuronal plasticity in the mammalian brain. Synaptic activation of transcription factors has been analyzed in the hippocampus using the long-term potentiation or enhancement (LTP/LTE) paradigm. Using this approach, several studies have identified transcription factors that are induced in hippocampal granule cells by NMDA receptor-dependent mechanisms; however, the link between long-term plasticity and activation of these genes has been called into question by reports suggesting that the thresholds for LTE and gene activation differ. To address this issue, we have used a chronic in vivo recording technique to monitor mRNA responses of several transcription factor genes to two different patterns of LTE-inducing electrical stimulation of entorhinal cortical afferents to hippocampus. One pattern consisted of 10 repetitions of a 20 or 25 msec train of pulses at 400 Hz (80 or 100 pulses total). This “10-train” pattern has been used in previous studies of LTE and produces robust synaptic enhancement lasting at least 3 d (Barnes, 1979). The other stimulation pattern consisted of 50 repetitions of a 20 msec train delivered at 400 Hz (400 pulses total), which is similar to parameters used in other studies reporting induction of c-fos in association with LTE (Dragunow et al., 1989; Jeffery et al., 1990; Abraham et al., 1992). Our results indicate that expression of zif268, monitored by in situ hybridization and immunostaining, is strongly induced by the 10-train stimulus pattern to levels similar to those induced by seizure activity. JunB mRNA levels are also modestly increased by the 10-train stimulus pattern; however, increases in JunB immunostaining were not detected. Neither c-fos nor c- jun mRNA were detectably induced by this stimulus. In contrast, the 50- train stimulus pattern resulted in a robust induction of c-fos and c- jun mRNA, in addition to zif268 and junB. Transcription factor responses to either stimulus pattern were blocked by the noncompetitive NMDA receptor antagonist MK-801. Identical transcription factor responses were observed in adult (6–12-month-old) and aged (23–26-month- old) rats, suggesting that synaptic mechanisms involved in these responses are preserved in aged animals. Analysis of LTE following either the 10- or 50-train stimulus patterns revealed identical magnitudes of initial induction and decay kinetics (approximately 3 d) and indicates that the 10-train stimulus pattern is sufficient to produce maximal synaptic enhancement.(ABSTRACT TRUNCATED AT 400 WORDS)
Enhancement of gamma-aminobutyric acid-activated chloride channel currents by lanthanides in rat dorsal root ganglion neurons
Authors: Ma JY , Narahashi T
Published: March 2018

Lanthanum was previously reported to potentiate the GABA-induced chloride currents reversibly by acting at a distinct site on the GABAA receptor-channel complex (Ma and Narahashi, 1993). We now report that all other lanthanides tested enhanced the GABA responses with greater efficiencies and produced inward currents by themselves. The rank order of efficacies of lanthanides to potentiate the GABA responses and to generate currents correlated inversely with the hydrated ionic radii of these ions. The GABA-induced currents were recorded from the rat dorsal root ganglion neurons in primary culture by the whole-cell patch-clamp technique. Lanthanides at 1 mM reversibly potentiated the GABA responses (times of control): lutetium (Lu3+) 12.4 +/- 0.1 > erbium (Er3+) 11.4 +/- 0.2 > terbium (Tb3+) 9.3 +/- 0.5 > europium (Eu3+) 5.4 +/- 0.4 > neodymium (Nd3+) 4.1 +/- 0.2 > cerium (Ce3+) 3.3 +/- 0.2 > lanthanum (La3+) 2.4 +/- 0.2 (n = 10). The enhancing effect of Tb3+ was dose dependent, with an EC50 356 +/- 12 microM (n = 10), and weakly voltage dependent, increasing with hyperpolarization. The amplitudes of currents induced by various lanthanides (1 mM) were (percentage of 10 microM GABA-induced current) Lu3+ 101 +/- 8 > Er3+ 57 +/- 8 > Tb3+ 33 +/- 3 > Eu3+ 20 +/- 2 > Nd3+ 14 +/- 2 approximately Ce3+ 13 +/- 0.6 > La3+ 10 +/- 0.2 (n = 4). Tb3+ reversibly induced currents in a dose- dependent manner with an EC50 of 863 +/- 0 microM (n = 5).(ABSTRACT TRUNCATED AT 250 WORDS)
Expression of beta 1 integrins in sensory neurons of the dorsal root ganglion and their functions in neurite outgrowth on two laminin isoforms
Authors: Tomaselli KJ , Doherty P , Emmett CJ , Damsky CH , Walsh FS , Reichardt LF
Published: March 2018

Integrins are heterodimeric receptors that mediate responses of neurons and many other cell types to components of the extracellular matrix. In the present article, we examine the roles of individual integrin receptors expressed by spinal sensory neurons of the dorsal root ganglion (DRG) in mediating interactions with laminin, an extracellular matrix glycoprotein that promotes neurite outgrowth. DRG neurons were shown to express three beta 1 integrins that have been shown in other cell types to function as laminin receptors--high levels of alpha 1 beta 1 and alpha 3 beta 1 and low levels of alpha 6 beta 1. In addition, DRG neurons were shown to express a known fibronectin receptor, alpha 5 beta 1, and an integrin with undefined ligands, alpha 6 beta 4. Function-inhibitory monoclonal antibodies specific for the alpha 1, alpha 2, alpha 3, alpha 5, and alpha 6 integrin subunits were used to determine the roles of individual integrins in mediating neurite outgrowth by DRG neurons on laminin. The results demonstrate that alpha 1 beta 1 and alpha 3 beta 1 function as laminin receptors on these neurons. As many as 18 distinct isoforms of laminin may exist, assembled as heterotrimers containing one each of the different A, B1, or B2 subunit homologs. In the present study, we characterize neurite outgrowth in response to two of these isoforms, the AeB1eB2e isoform and the AmB1eB2e isoform. Results utilizing DRG neurons and a pheochromocytoma cell line (PC12) indicate that these two isoforms exhibit differential selectivities for the alpha 1 beta 1 and alpha 3 beta 1 integrins.(ABSTRACT TRUNCATED AT 250 WORDS)
Physiological, morphological, and histochemical characterization of three classes of interneurons in rat neostriatum
Authors: Kawaguchi Y
Published: March 2018

Interneurons in lateral part of neostriatum were studied in isolated slices from juvenile rats (16–20 d postnatal) by whole-cell, current- clamp recording at 33–34 degrees C, followed by intracellular staining with biocytin and double immunocytochemical or histochemical staining for parvalbumin, ChAT, and NADPH diaphorase. Medium-sized spiny neurons (MS cells) had distal dendrites with many spines and were likely projection cells, while interneurons had dendrites with fewer spines. The neostriatal interneurons could be further divided into three classes by physiological, chemical, and morphological criteria. The first class of interneurons (fast-spiking cells, FS cells) fired very short-duration action potentials with short-duration afterhyperpolarizations at constant spike frequency during depolarizing current pulses. FS cells had more negative resting potentials and lower input resistances than the other two classes. At depolarized potentials, FS cells fired repetitive spikes in response to synaptic excitation. FS cells were immunoreactive for parvalbumin. As all parvalbumin-immunoreactive cells in the neostriatum were also immunoreactive for GABA, FS cells were considered to be GABAergic. FS cells were further divided into two morphological types: FS cells with local dendritic fields and FS cells with extended dendritic fields. The axons of both types of FS cells had their densest collateralization within or near their dendritic fields. The other two classes of interneuron, PLTS cells (persistent and low-threshold spike cells) and LA cells (long-lasting afterhyperpolarization cells), were distinguished from FS cells by longer-duration action potentials and larger input resistances, had less negative resting potentials, and had longer-lasting afterhyperpolarizations. Afterhyperpolarizations of PLTS cells had a shorter time to peak than those of LA cells. PLTS cells fired both Na(+)-dependent, persistent depolarization spikes and Ca(2+)- dependent, low-threshold spikes in addition to fast spikes. Low- threshold spikes in PLTS cells were induced only from hyperpolarized potentials. Both persistent depolarizations and low-threshold spikes could also be evoked by synaptic activation. PLTS cells were histochemically identified as NADPH diaphorase-positive cells. As all NADPH diaphorase-positive cells in the same tissue were immunoreactive for nitric oxide (NO) synthase, PLTS cells were considered to release NO. PLTS cells had the largest axonal fields. Some PLTS cells appeared to have two axonal origins from the somata and dendrites. LA cells were mostly large aspiny cells with Ca(2+)-dependent long-lasting afterhyperpolarizations and strong time-dependent hyperpolarizing rectification. As this slowly occurring anomalous rectification was blocked by 2 mM cesium, this potential was considered to be due to activation of Ih.(ABSTRACT TRUNCATED AT 400 WORDS)
Low-threshold Ca2+ current and its role in spontaneous elevations of intracellular Ca2+ in developing Xenopus neurons [published erratum appears in J Neurosci 1994 Mar;14(3):following table of contents]
Authors: Gu X , Spitzer NC
Published: March 2018

Amphibian spinal neurons exhibit spontaneous elevations of intracellular calcium at early stages of development. The underlying calcium influx involves high-voltage-activated (HVA) currents. To begin to understand how they are triggered, we have studied the biophysical properties and developmental function of low-voltage-activated (LVA) T- type calcium current of neurons cultured from the embryonic neural plate. T current was recorded from young neurons (6–9 hr in vitro) and from mature neurons (18–48 hr in vitro) using whole-cell voltage clamp. For both young and mature neurons, T current has a low threshold and is activated at membrane potentials positive to -60 mV in 2 mM extracellular calcium. The current is maximal at -35 mV with a mean peak amplitude of approximately 50 pA. Nickel blocks both LVA and HVA currents, but the former are 20-fold more sensitive. Amiloride also blocks T current selectively. T current is recorded in 87% of young neurons. This percentage drops to 67% in mature neurons after 1 d in culture and to 35% in mature neurons after 2 d in culture. There are no significant developmental changes in T current threshold, peak density, time course of activation and inactivation, and pharmacological sensitivity to blockers from 6 to 48 hr in culture. Spontaneous transient calcium elevations in young neurons assayed by fluo-3 fluorescence are blocked by nickel or amiloride at concentrations that specifically block T current. T current has the lowest threshold among other inward currents in young neurons. Moreover, mathematical simulations show that T current lowers the threshold of the action potential by 15 mV. We conclude that T current can depolarize cells and trigger action potentials, and constitutes part of the cascade of events leading to spontaneous elevations of intracellular calcium in cultured neurons at early stages of differentiation.
Fine-structural alterations and clustering of developing synapses after chronic treatments with low levels of NMDA
Authors: Yen LH , Sibley JT , Constantine-Paton M
Published: March 2018

In the visual pathway of frogs it is possible to apply low levels of NMDA chronically to the optic tectum and study the mechanisms underlying the stabilization of synapses developing within the CNS. Earlier studies (Cline and Constantine-Paton, 1990) found that chronic NMDA treatment of tecta innervated by two retinas results in a reduction of branching within the terminal arbors of retinal ganglion cells (RGCs). We now report that this same chronic NMDA treatment produces fine-structural changes in synaptic morphology as well as local synaptic rearrangements within the retinotectal neuropil. Chronic NMDA treatment of doubly innervated tecta was associated with a thickening or darkening of both pre- and postsynaptic densities. These changes in synapse morphology were restricted to the superficial neuropil of tecta in regions where reductions in branches of RGC axonal arbors were observed at the light microscopic level. The fine- structural effects were absent from similarly treated tecta innervated by only one eye, where RGC axonal arbor pruning was not observed. Stereological analyses indicated that the incidence of two or more presynaptic profiles converging on the same postsynaptic process was significantly increased in the NMDA-treated, doubly innervated tecta. This observed increase in synaptic clustering was not associated with a larger synaptic active zone, or with an increase in the number of synapses per unit volume. These data are discussed in the context of the hypothesis that chronic NMDA treatment raises the threshold for synapse stabilization in tectal neurons, causing the selective loss of poorly correlated synapses of both retinal and non-retinal origin from tectal neuropil that is innervated by two retinas: increased pre- and postsynaptic thickening could reflect greater efficiency in the remaining synaptic contacts and their closer spatial proximity on the same postsynaptic process is consistent with greater cooperativity and less competition.
Protein tyrosine phosphatases expressed in the developing rat brain
Authors: Sahin M , Hockfield S
Published: March 2018

Previous studies of the developing nervous system have shown that cell- cell and cell-matrix interactions are involved in a variety of processes such as the proliferation, migration, and differentiation of neurons. While many cell-surface molecules have been identified, the signal transduction mechanisms through which they modify cellular responses are poorly understood. Recent studies have described a new and large family of enzymes, protein tyrosine phosphatases (PTPases), that may play a key role in transduction of cell surface events. Opposing the actions of protein tyrosine kinases (PTKs), PTPases can determine the state of tyrosine phosphorylation of a protein and regulate its function. Within the family of PTPases, two subgroups have been characterized: low-molecular-weight cytoplasmic (nonreceptor) PTPases and high-molecular-weight transmembrane (receptor) PTPases. Many receptor PTPases have fibronectin type III and/or Ig-like domains in their extracellular domains, suggesting that they have dual functions: cell adhesion and signal transduction. Such molecules may play a role in cellular recognition events that mediate the accurate assembly of the nervous system. Using polymerase chain reaction with degenerate primers and a neonatal rat cortex cDNA library, we have identified a number of putative PTPase domains expressed in brain. Three are characterized here. These three sequences are most abundantly expressed in the developing cortex and so are named cortex-enriched protein tyrosine phosphatases (CPTPs) 1, 2, and 3. CPTP1 and CPTP3 show sequence homology to receptor PTPases and detect multiple high- molecular-weight mRNAs that are expressed preferentially in the developing CNS. Analysis of a longer cDNA indicates that CPTP1 and CPTP3 are the first and second phosphatase domains of a single receptor PTPase. CPTP2 identifies a single, smaller mRNA species with sequence homology to nonreceptor PTPases. Within the CNS, mRNAs detected by all three CPTPs are expressed at highest levels during prenatal and early postnatal days and are downregulated in the adult. In situ hybridization demonstrates that the CPTPs are expressed by progenitor cells and developing neurons. The spatial and temporal regulation of CPTPs suggests that they may play a role in neuronal development.
Relative properties and localizations of synaptic vesicle protein isoforms: the case of the synaptophysins
Authors: Fykse EM , Takei K , Walch-Solimena C , Geppert M , Jahn R , De Camilli P , Sudhof TC
Published: March 2018

Synaptophysins are abundant synaptic vesicle proteins present in two forms: synaptophysin, also referred to as synaptophysin I (abbreviated syp I), and synaptoporin, also referred to as synaptophysin II (abbreviated syp II). In the present study, the properties and localizations of syp I and syp II were investigated to shed light on their relative functions. Our results reveal that syp II, similar to syp I, is an abundant, N-glycosylated membrane protein that is part of a heteromultimeric complex in synaptic vesicle membranes. Cross-linking studies indicate that syp II is linked to a low-molecular-weight protein in this complex as has been observed before for syp I. Furthermore, after transfection into CHO cells, syp II, similar to syp I, is targeted to the receptor-mediated endocytosis pathway. Immunocytochemistry of rat brain sections reveals that syp II expression is highly heterogeneous, with high concentrations of syp II only in selected neuronal populations, whereas syp I is more homogeneously expressed in most nerve terminals. In general, nerve terminals expressing syp II also express syp I. In addition to high levels of syp II observed in selected neurons, a rostrocaudal gradient of syp II expression was observed in the cerebellar cortex. Immunoelectron microscopy confirmed that syp II is localized to synaptic vesicles. Immunoprecipitations of synaptic vesicles from rat brain with antibodies to syp I demonstrated that syp II is colocalized with syp I on the same vesicles. However, after detergent solubilization, no coimmunoprecipitations of the two proteins were observed, suggesting that they are not complexed with each other although they are on the same vesicles. Together our results demonstrate that syp I and syp II have similar properties and are present on the same synaptic vesicles but do not coassemble. The presence of the two proteins in the same nerve terminal suggests that they have similar but nonidentical functions and that the relative abundance of the two proteins may contribute to the functional heterogeneity of nerve terminals.
Melatonin ameliorates brain oxidative stress and upregulates senescence marker protein-30 and osteopontin in a rat model of vascular dementia
Authors: Bin-Jaliah I , Sakr HF
Published: March 2018

The aim of this study was to investigate the effect of melatonin on oxidative stress and senescence marker protein-30 (SMP30) as well as osteopontin (OPN) expression in the hippocampus of rats subjected to vascular dementia (VD). A total of 72 male rats were divided into six groups (n = 12 each) as follows: (i) untreated control (CON), (ii) sham-operated group, (iii) sham-operated + melatonin, (iv) rats exposed to VD induced by permanent bilateral occlusion of the common carotid arteries (BCCAO) leading to chronic cerebral hypoperfusion, (v) rats exposed to VD + melatonin, and (vi) rats exposed to VD + donepezil (DON). At the end of experiment, the hippocampal levels of acetylcholine (ACh), norepinephrine (NE), and dopamine (Dop) were measured. Expression of OPN was determined using immunohistochemistry, and SMP30 expression was determined using real-time PCR in the hippocampus. Hippocampal thiobarbituric acid reactive substances (TBARS) and total antioxidant capacity (TAC) were evaluated. The BCCAO group showed significantly decreased TAC (p < 0.05) and significantly increased in TBARS levels compared with the CON group. In addition, BCCAO significantly decreased (p < 0.05) the expression of both OPN and SMP30 and the levels of ACh, NE, and Dop in the hippocampus compared with CON treatment. Treatment with melatonin significantly increased OPN and SMP30 expression and ACh, NE, and Dop levels in the hippocampus with amelioration of the oxidative stress compared with BCCAO rats. Melatonin might produce a neuroprotective effect through its antioxidant action and by increasing the expression of SMP30 and OPN that is not comparable with that of DON.
Moderate hypothermia and responses to calcium channel blockers – Role of the nitric oxide
Authors: Canbolat S , Nurullahoglu Atalik KE
Published: March 2018

Moderate hypothermia (25–31 °C) may have a significant influence on vascular tone. At present, very little is known about the role of endothelial nitric oxide on the hypothermia-induced responses. In this study, we investigated the effect of hypothermia (to 28 °C) on the vasodilatation induced by verapamil, a phenylalkylamine calcium channel blocker (10−9–3 × 10−4 M) and dihydropyridines, amlodipine (10−9–3 × 10−4 M), and benidipine (10−9–10−3 M) on 5-hydroxytryptamine (5-HT or serotonin) precontracted calf cardiac veins. Furthermore, the role of nitric oxide in the hypothermia-induced responses was analyzed. Ring preparations of veins obtained from calf hearts were suspended in organ baths containing 15 ml of Krebs–Henseleit solution, maintained at 37 °C, and continuously gassed with 95% O2–5% CO2. After a resting period, verapamil, amlodipine, and benidipine were applied cumulatively on serotonin (10−6 M) precontracted calf cardiac vein rings and induced concentration-dependent relaxations. In another part of the study, the medium temperature was decreased to 28 °C after the preparations were contracted with 5-HT, then cumulative concentrations of verapamil, amlodipine, or benidipine were added. During hypothermia, the pIC50 value, but not the maximal response, to all blockers were significantly higher than at 37 °C. Hypothermia in the presence of NG-nitro-l-arginine methyl ester (L-NAME, 10−4 M) decreased the pIC50 and Emax values to verapamil, amlodipine, and benidipine. Only one blocker was tested in each preparation. These results suggest that nitric oxide may play a role in the hypothermia-induced changes in vasodilation caused by verapamil, amlodipine, and benidipine in calf cardiac vein, but further research is needed to explain the complete mechanism.
Surface electromyographic evaluation of the neuromuscular activation of the inspiratory muscles during progressively increased inspiratory flow under inspiratory-resistive loading
Authors: Sekiguchi H , Tamaki Y , Kondo Y , Nakamura H , Hanashiro K , Yonemoto K , Moritani T , Kukita I
Published: March 2018

This study aimed to evaluate neuromuscular activation in the scalene and sternocleidomastoid muscles using surface electromyography (EMG) during progressively increased inspiratory flow, produced by increasing the respiratory rate under inspiratory-resistive loading using a mask ventilator. Moreover, we attempted to identify the EMG inflection point (EMGIP) on the graph, at which the root mean square (RMS) of the EMG signal values of the inspiratory muscles against the inspiratory flow velocity acceleration abruptly increases, similarly to the EMG anaerobic threshold (EMGAT) reported during incremental-resistive loading in other skeletal muscles. We measured neuromuscular activation of healthy male subjects and found that the inspiratory flow velocity increased by approximately 1.6-fold. We successfully observed an increase in RMS that corresponded to inspiratory flow acceleration with ρ ≥ 0.7 (Spearman’s rank correlation) in 17 of 27 subjects who completed the experimental protocol. To identify EMGIP, we analyzed the fitting to either a straight or non-straight line related to the increasing inspiratory flow and RMS using piecewise linear spline functions. As a result, EMGIP was identified in the scalene and sternocleidomastoid muscles of 17 subjects. We believe that the identification of EMGIP in this study infers the existence of EMGAT in inspiratory muscles. Application of surface EMG, followed by identification of EMGIP, for evaluating the neuromuscular activation of respiratory muscles may be allowed to estimate the signs of the respiratory failure, including labored respiration, objectively and non-invasively accompanied using accessory muscles in clinical respiratory care.
Heat shock proteins and cardiovascular disease
Authors: Rodríguez-Iturbe B , Johnson RJ
Published: March 2018

The development of stress drives a host of biological responses that include the overproduction of a family of proteins named heat shock proteins (HSPs), because they were initially studied after heat exposure. HSPs are evolutionarily preserved proteins with a high degree of interspecies homology. HSPs are intracellular proteins that also have extracellular expression. The primary role of HSPs is to protect cell function by preventing irreversible protein damage and facilitating molecular traffic through intracellular pathways. However, in addition to their chaperone role, HSPs are immunodominant molecules that stimulate natural as well as disease-related immune reactivity. The latter may be a consequence of molecular mimicry, generating cross-reactivity between human HSPs and the HSPs of infectious agents. Autoimmune reactivity driven by HSPs could also be the result of enhancement of the immune response to peptides generated during cellular injury and of their role in the delivery of peptides to the major histocompatibility complex in antigen-presenting cells. In humans, HSPs have been found to participate in the pathogenesis of a large number of diseases. This review is focused on the role of HSPs in atherosclerosis and essential hypertension.
Effect of iloprost on contractile impairment and mitochondrial degeneration in ischemia-reperfusion of skeletal muscle
Authors: Bagis Z , Ozeren M , Buyukakilli B , Balli E , Yaman S , Yetkin D , Ovla D
Published: March 2018

Purpose

Acute lower extremity ischemia is still a main cause of mortality and morbidity in orthopedic traumatology and reconstructive surgery. In acute lower extremity ischemia, the skeletal muscles are the tissues that are the most vulnerable to ischemia. The aim of this study was to evaluate the effects of iloprost (IL) therapy on skeletal muscle contractile impairment and mitochondrial degeneration in an acute lower extremity ischemia-reperfusion rat model.

Main Methods

Forty Wistar albino rats were randomly divided into a control group and four experimental groups. Experimental groups were either subjected to 2 h of lower extremity ischemia followed by a 4-h reperfusion period or to 4 h of ischemia followed by an 8-h reperfusion period. Except for the animals in the control group, all animals received IL (1 ng/kg/min) or saline (1 ml/kg) by intraperitoneal infusion for 10 min immediately before reperfusion. At the end of the recording of skeletal muscle electrical activity and contractility, all rats were sacrificed by decapitation and muscle samples of lower extremity were immediately harvested for histopathologic analyses.

Results

After ischemia-reperfusion, a breakdown in the force–frequency curves of extensor digitorum longus muscle was observed, showing the diminished muscle contractility. However, IL significantly improved muscle contractility following injury induced by 2 h of ischemia followed by a 4-h reperfusion period. In addition, IL partially ameliorated mitochondrial degeneration in the muscle cells of ischemia groups.

Conclusion

This study indicates that immediate IL therapy repairs muscle damage especially after 2 h of ischemia and 4 h of reperfusion and therefore that IL improves contractile function.
What we do and do not know about women and kidney diseases; Questions unanswered and answers unquestioned: Reflection on World Kidney Day and International Woman’s Day
Authors: Piccoli GB , Alrukhaimi M , Liu Z-H , Zakharova E , Levin A ,   World Kidney Day Steering Committee
Published: March 2018

Chronic kidney disease (CKD) affects approximately 10% of the world’s adult population; it is within the top 20 causes of death worldwide, and its impact on patients and their families can be devastating. World Kidney Day and International Women’s Day in 2018 coincide, thus offering an opportunity to reflect on the importance of women’s health and specifically their kidney health, on the community, and the next generations, as well as to strive to be more curious about the unique aspects of kidney disease in women so that we may apply those learnings more broadly. Girls and women, who make up approximately 50% of the world’s population, are important contributors to society and their families. Gender differences continue to exist around the world in access to education, medical care, and participation in clinical studies. Pregnancy is a unique state for women, which not only offers an opportunity for diagnosis of kidney disease, but also states where acute and chronic kidney diseases may manifest, and which may impact future generations with respect to kidney health. There are various autoimmune and other conditions that are more likely to impact women with profound consequences for childbearing, and on the fetus. Women have different complications on dialysis than men and are more likely to be donors than recipients of kidney transplants. In this editorial, we focus on what we do and do not know about women, kidney health, and kidney disease and what we might learn in the future to improve outcomes worldwide.
Assessing State Support for the Development of International Economic Cooperation: a Case of Polish Trade Support Institutions’ Export Recommendations for Turkey
Authors:   University of Wrocław (Poland), J. Chmiel Oskar
Published: March 2018

In times of increasing significance for national policies which support international economic cooperation, a special role is played by state trade support institutions (TSIs). This paper investigates whether such TSIs can be said to operate effectively, through an analysis of one essential element of the support provided to domestic entrepreneurs, namely export recommendations. The recommendations provided by Polish TSIs in respect of Turkey is employed as a case study. The theory of comparative advantage along with a neo-institutional perspective provide the conceptual framing for this analysis, in conjunction with both desk research, document analysis, and selected economic indices. Factors such as trade potential, comparative advantages, and the competitiveness of selected product groups exported by Polish firms to Turkey were also taken into account. The findings largely indicate that TSI export recommendations are adequate, and the majority of the recommended industries demonstrated considerable sales opportunities. Nevertheless, some discrepancies were also noted, which should be an issue for further investigation by both researchers and TSI analysts. Furthermore, the case study in this paper demonstrates that the choices within economic promotion policy – despite its partition between variously-oriented TSIs - were made on the basis of economic rationality.
Set the Torturers Free: Transitional Justice and Peace vs Justice Dilemma in Burma/Myanmar
Authors:   Jagiellonian University in Kraków (Poland), Lubina Michał
Published: March 2018

Burma/Myanmar seems to be a perfect ground for transitional justice with both long-failed transitions to democracy that seemed to succeed in 2015 finally and smouldering civil war taking place there since 1948 (since the 1990s limited to Borderlands). Unfortunately, the political realities in Burma/Myanmar make it unlikely, if not impossible, for transitional justice to be applicable in Burma/Myanmar. The victorious in 2015 elections democratic opposition party, National League for Democracy (NLD) came to power thanks to the political deal with the former military government and is consequently being forced to cohabitate politically with the army that still holds critical political checks over the government. It made NLD’s leader, Aung San Suu Kyi to conduct moderate domestic policy without trying to charge the generals for their former crimes. In this circumstances, transitional justice is unwanted by mainstream political actors (NLD, the army) and seen as threatening to peace by many in the Myanmar society. This approach firmly places Burma/Myanmar on one side of the ‘peace vs justice’ dilemma. It answers the “torturer problem”, one of the central problems of transitional justice – how to deal with members of the previous regime which violated human rights – in ‘old fashion’ way, by granting them full amnesty. As such Burma/Myanmar case also falsifies an optimistic claim that transitional justice is necessary for political reforms.
“Right to Truth” and Memory Laws: General Rules and Practical Implications
Authors:   Polish Academy of Sciences (Poland), Gliszczyńska-Grabias Aleksandra , Baranowska Grażyna
Published: March 2018

The “right to truth” relates to the obligation of the state to provide information about the circumstances surrounding serious violations of human rights. Despite its increasing recognition, the concept raises questions as to its scope and implementation as well as its existence as a free-standing right. Similarly, “memory laws” relate to the way states deal with their past. However, there are certain „memory laws” that, while officially serving as a guarantee for accessing historical truth, lead to its deformation. As a result, an “alternative” truth, based on the will of the legislators, is being imposed. In this article, the authors elaborate on the general nature of the new legal phenomenon of the „right to truth”, as a tool of transitional justice, in particular in the context of both providing and abusing historical truth by the legislators, through the instrument of “memory laws”.
Co-Production of Public Services in Terms of the Polish Experience
Authors:   10.15804/ppsy2018108, Gawłowski Robert
Published: March 2018

Co-production of public services is an increasingly popular tool in public management, although it is still a new phenomenon in Poland. Despite the attention researchers give to co-production, some significant gaps remain. In this article, the author attempts to examine the legal possibility of implementing co-production by the Polish local government by local initiative and Solecki Fund. The article aims to examine how major Polish cities gathered in Union in Polish Metropolises used local initiatives. The next step in research is to find out how Solecki Fund is spread among rural areas according to statistical data. It is proved that only a handful of local governments in Poland are truly engaged in co-production. However, Solecki Fund can be shown as an excellent example of citizens’ engagement. It is presented a possible agenda on what can be done to make co-production more popular and used on a regular basis not only in metropolitan but also rural areas.
Provoking Debate on Central European Security
Authors:   American University in the Emirates (UAE), Michnik Wojciech
Published: March 2018

The seminar focused on the Security Challenges in Central Europe organised by PPSY was held in Toruń on February 21, 2017. The leading topic of this event could not have been apter as the last years in the region brought back serious questions about stability and security of the region. From the domestic challenges – like the rise of populist movements; to more resurgent foreign policy of Russian Federation; instability of so-called Eastern flank; through the questions about coherence of both NATO and the European Union – Central European states found themselves in a situation unprecedented since the end of the Cold War. It can be even argued that Central Europe come to strategic crossroads that would determine future of the regions and its countries in particular.
Discussing Changes in Contemporary International Relations
Authors:   Nicolaus Copernicus University (Poland), Dahl Michał
Published: March 2018

The paper reports the 9th Polish Conference on International Relations: 2017 – a Year of a Change organized by the Faculty of Political Science and International Studies at Nicolaus Copernicus University in Toruń on June 2, 2017. It presents not only the scope and process of this years’ conference but also briefly describes the idea of annual meetings of young Polish scholars interested in widely understood international relations. The conference report presents accompanying events of the conference, which gave its ninth edition unique atmosphere. It also points out the way this years’ conference contributed to the unification of the community of students and PhD students in Poland who are researching a variety of subjects related to international relations.