bluuebunny/crossref_metadata_2025 huggingface dataset:
Loss of glutamate decarboxylase mRNA-containing neurons in the rat dentate gyrus following pilocarpine-induced seizures
Authors: Obenaus A , Esclapez M , Houser CR
Published: March 2018

In situ hybridization methods were used to determine if glutamic acid decarboxylase (GAD) mRNA-containing neurons within the hilus of the dentate gyrus are vulnerable to seizure-induced damage in a model of chronic seizures. Sprague-Dawley rats were injected intraperitoneally with pilocarpine, and the hippocampal formation was studied histologically at 1, 2, 4, and 8 week intervals after pilocarpine- induced seizures. In situ hybridization histochemistry, using a digoxigenin-labeled GAD cRNA probe, demonstrated a substantial decrease in the number of GAD mRNA-containing neurons in the hilus of the dentate gyrus in the pilocarpine-treated rats as compared to controls at all time intervals. Additional neuronanatomical studies, including cresyl violet staining, neuronal degeneration methods, and histochemical localization of glial fibrillary acidic protein, suggested that the decrease in the number of GAD mRNA-containing neurons was related to neuronal loss rather than to a decrease in GAD mRNA levels. The loss of GAD mRNA-containing neurons in the hilus contrasted with the relative preservation of labeled putative basket cells along the inner margin of the granule cell layer. Quantitative analyses of labeled neurons in three regions of the dentate gyrus in the 1 and 2 week groups showed statistically significant decreases in the mean number of GAD mRNA-containing neurons in the hilus of both groups of experimental animals. No significant differences were found in the molecular layer or the granule cell layer, which included labeled neurons along the lower margin of the granule cell layer. The results indicate that, in this model, a subpopulation of GAD mRNA- containing neurons within the dentate gyrus is selectively vulnerable to seizure-induced damage. Such differential vulnerability appears to be another indication of the heterogeneity of GABA neurons.
Reduced levels of acetylcholine receptor expression in chick ciliary ganglion neurons developing in the absence of innervation
Authors: Arenella LS , Oliva JM , Jacob MH
Published: March 2018

Chick ciliary ganglion neurons receive innervation from a single source, the accessory oculomotor nucleus (AON), and nicotinic ACh receptors (AChRs) mediate chemical synaptic transmission through the ganglion. Previous experiments examining the developmental expression of AChRs in embryonic chick ciliary ganglion neurons in situ have shown that AChR levels increase substantially in the neurons at the time of innervation. Prior to synapse formation, few AChRs are detected in the neurons. In the present experiments, the role of presynaptic inputs in inducing an increase in AChRs was established by examining AChR levels in ciliary ganglion neurons that have been deprived of innervation by surgical ablation of the AON prior to synapse formation. AChR levels were dramatically reduced in neurons of input-deprived ganglia as compared to control innervated neurons at all developmental stages examined from embryonic day (ED) 5 to ED 12 as determined by indirect immunocytochemical labeling of frozen ganglion sections with the anti- AChR monoclonal antibody mAb 35, and light microscopy. In contrast, neuronal somata of input-deprived and control ganglia had equivalent levels of immunolabeling for three other components, a transmembrane glycoprotein of synaptic vesicles, SV2, and two microtubule-associated proteins, MAP 1B and MAP 2, from ED 5 up to ED 10. The results demonstrate that presynaptic inputs specifically increase the levels of AChR expression in developing neurons. In addition, changes in the levels of immunolabeling for AChRs, SV2, MAP 1B, and MAP 2 in neuronal somata after ED 10 demonstrate that other major developmental events also influence the levels of these components in neurons. Declines in the intensity of AChR, SV2, MAP 1B, and MAP 2 immunolabeling within a subset of neuronal somata in both operated and control ganglia at ED 10 and 12 coincide with the period of neuronal cell death. Increases in AChR labeling in the rest of the neuronal population of input-deprived ganglia at ED 12 suggest that, in addition to innervation, synapse formation with the peripheral target tissue influences AChR levels in developing neurons in situ.
Auditory compensation for early blindness in cat cerebral cortex
Authors: Rauschecker JP , Korte M
Published: March 2018

Single-neuron activity was recorded in the caudal part of the anterior ectosylvian (AE) cortex of cats that had been deprived of vision for several years by means of binocular lid suture shortly after birth and in normal control animals. Over 300 neurons were tested in each group with auditory, visual, and somatosensory stimuli. We confirmed the existence of an anterior ectosylvian visual area (AEV) in the fundus and ventral bank of the AE sulcus. Neurons in AEV had purely visual responses in normal cats. In visually deprived cats, by contrast, only a minority of cells in this area still responded to visual stimulation. Instead, most cells reacted vigorously to auditory and, to some extent, somatosensory stimuli. The few remaining visual neurons were also driven by auditory or somatosensory stimuli. No increase in the number of unresponsive neurons was found. It appears, therefore, that a cortical region that normally represents visual activity can become driven by auditory or somatosensory activity as a result of visual deprivation. Our results imply that early blindness causes compensatory increases in the amount of auditory cortical representation, possibly by an expansion of nonvisual areas into previously visual territory. In particular, they provide evidence for the existence of neural mechanisms for intermodal compensatory plasticity in the cerebral cortex of young animals. The changes described here may also provide the neural basis for a behavioral compensation for early blindness described elsewhere.
Neural substrates of visual stimulus-stimulus association in rhesus monkeys
Authors: Murray EA , Gaffan D , Mishkin M
Published: March 2018

Rhesus monkeys learned 10 visual stimulus-stimulus association, or paired associates. They then received bilateral removals of either the amygdaloid complex and underlying cortex, the hippocampal formation and underlying cortex, or both combined, or they were retained as unoperated controls. After surgery or rest, the monkeys were tested for their retention of the preoperatively learned set of paired associates, as well as for their ability to learn new associations of the same type. Both unoperated controls and hippocampectomized monkeys relearned the preoperatively trained set of paired associates almost immediately. By contrast, monkeys with amygdala removals were moderately retarded in relearning, and monkeys with combined amygdala and hippocampal ablations were severely retarded. When confronted with new sets of visual stimuli, monkeys with amygdala removals or hippocampal removals learned new sets of paired associates at the same rate as the controls, whereas monkeys with the combined ablation were again profoundly retarded. Only one monkey with the combined lesion was able to learn new stimulus-stimulus associations to criterion, and then only after extensive training, despite the ability of all three animals in this group to perform delayed matching-to-sample with the same stimuli and the same intraatrial delays as those used in the paired associate task. At the end of the main experiment, two of the unoperated controls received bilateral ablations of the rhinal cortex. These monkeys showed the same level of difficulty in learning new paired associates as the animals in the main experiment that had received the combined amygdala plus hippocampal ablations. The results implicate the medial temporal lobe, and particularly the rhinal cortex, in the formation of stimulus- stimulus associative memories.
Postsynaptic potentials mediated by GABA and dopamine evoked in stellate glial cells of the pituitary pars intermedia
Authors: Mudrick-Donnon LA , Williams PJ , Pittman QJ , MacVicar BA
Published: March 2018

Studies have shown that many glial cells in the CNS possess receptors for neurotransmitters and that synapse-like contacts exist between glial cells and axonal terminals. Although synapse-like contacts are present between the glial cells (stellate cells) of the pituitary pars intermedia and the axons from the arcuate nucleus, it is not known whether these cells are under synaptic control. The objective of the present study was to determine whether transmitter-mediated postsynaptic potentials occurred in the stellate cells of the rat pituitary pars intermedia. Whole pituitaries were maintained in vitro, and a stimulating electrode was placed on the stalk to activate afferent fibers. Intracellular recordings were obtained with sharp microelectrodes. Stellate cells showed electrophysiological characteristics of macroglia including a resting potential more negative than -65 mV, low input resistance (< 50 M omega), and no detectable voltage-activated conductances. Single-pulse afferent nerve (stalk) stimulation evoked a [Ca2+]o-dependent postsynaptic response in the stellate cells consisting of a depolarization (< 500 msec) and a long-lasting hyperpolarization (45–75 sec). The depolarization was mimicked by GABA application and blocked by the GABAA antagonist bicuculline (100 microM). Repetitive stimulation of the stalk increased the amplitude and prolonged the GABA-mediated depolarization, during which a decrease in input resistance was observed. The hyperpolarization was mimicked by dopamine and blocked by the D2 antagonists sulpiride (2 microM) and domperidone (10 microM). Nipecotic acid (100 microM; an inhibitor of GABA uptake) or GBR 12909 (15 microM; an inhibitor of dopamine uptake) had minimal effects on the synaptic responses.(ABSTRACT TRUNCATED AT 250 WORDS)
Modulation of different K+ currents in Drosophila: a hypothetical role for the Eag subunit in multimeric K+ channels
Authors: Zhong Y , Wu CF
Published: March 2018

We examined the role of the ether a go-go (eag) gene in modulation of K+ currents and the possibility of its protein product Eag as a subunit in the heteromultimeric assembly of K+ channels by voltage-clamp analysis of larval muscle membrane currents. Previous DNA sequence studies indicate that the eag gene codes for a polypeptide homologous to, but distinct from, the Shaker (Sh) K+ channel subunits (Warmke et al., 1991), and electrophysiological recordings revealed allele- specific effects of eag on four identified K+ currents in Drosophila larval muscles (Zhong and Wu, 1991). Further studies of eag alleles indicated that none of the eag mutations, including alleles producing truncated mRNA messages, eliminate any of the four K+ currents, and that the mutational effects exhibit strong temperature dependence. We found that both W7, an antagonist of Ca2+/calmodulin, and cGMP analogs modulated K+ currents and that their actions were altered or even abolished by eag mutations. These results suggest a role of eag in modulation of K+ currents that may subserve integration of signals at a converging site of the two independent modulatory pathways. The Sh locus is known to encode certain subunits of the IA channel in larval muscle. The existence of multiple eag and Sh alleles enabled an independent test of the idea of Eag as a K+ channel subunit by studying IA in different double-mutant combinations. An array of allele-specific interaction between eag and Sh was observed, which reflects a close association between the Sh and eag subunits within the IA channel. Taken together, our data strengthen the possibility that the eag locus provides a subunit common to different K+ channels. The role of the eag subunit for modulating channels, as opposed to that of Sh subunits required for gating, selectivity, and conductance of the channel, suggest a combinatorial genetic framework for generating diversified K+ channels.
Development of neural selectivity for birdsong during vocal learning
Authors: Volman SF
Published: March 2018

Juvenile white-crowned sparrows learn to sing by first memorizing an adult's song and then progressively matching their vocalizations to this model during plastic song. Previous studies have shown that neurons in the song-system nucleus HVC of adult sparrows respond preferentially to a bird's own song. In this study, the auditory selectivity of HVC neurons in subadult birds was examined. In young, nonsinging birds who had been song tutored, these cells responded to song stimuli, and at some recording sites had distinct preferences for one song or another. As a population, however, HVC neurons in these birds showed no preference for familiar song. They were no more likely to prefer normal tutor song to reversed tutor song or to the song of another white-crowned subspecies. By contrast, in birds producing plastic song, HVC neurons were selective for the bird's own songs, even in preference to their tutor song. Therefore, during song learning the response properties of HVC neurons appear to be dynamically modified, perhaps by auditory feedback from the bird's own vocalizations. The emergence of song selectivity during plastic song may be significant both for song learning and for song perception in adult birds.
The functional anatomy of limbic status epilepticus in the rat. II. The effects of focal deactivation
Authors: White LE , Price JL
Published: March 2018

Limbic status epilepticus was induced in awake, unrestrained rats by electrically stimulating the anterior piriform cortex or the basal amygdaloid nucleus for about 40 min. As described in the preceding article (White and Price, 1993), one of four stable forms of status may be induced. Each form is characterized on the basis of its behavioral and electroencephalographic manifestations, and its distinct patterns of 14C-2-deoxyglucose uptake and Fos-like immunoreactivity. This study was directed at identifying the epileptogenic foci of the two major forms of status, types II and III, by deactivating the basal amygdaloid nucleus, ventral hippocampal formation, amygdalohippocampal area, or anterior piriform cortex during these seizure states. Infusions of the local anesthetic lidocaine, the GABA agonist muscimol, or a vehicle solution alone were made into each of these structures during ongoing type II or type III status. The major finding is that deactivation of the basal amygdaloid nucleus terminated both types of status. This indicates that the basal nucleus is primarily responsible for the generation of widespread status epilepticus activity. Deactivation of the ventral hippocampal formation did not terminate the subconvulsive levels of status, but did prevent the recurrent development of sustained seizures with facial and forelimb clonus that characterize type III status. These models of status epilepticus may be particularly important for understanding seizure mechanisms that are not dependent upon the hippocampal formation. The possible clinical relevance of these findings is discussed in relation to temporal lobe epilepsy.
Two structural adaptations for regulating transmitter release at lobster neuromuscular synapses
Authors: Walrond JP , Govind CK , Huestis SE
Published: March 2018

The distal accessory flexor muscle (DAFM) in the lobster (Homarus americanus) walking leg consists of 5 muscle fiber bundles. All five bundles, one proximal, one distal, and 3 medial, are innervated by one excitatory and one inhibitory motor neuron. Both neurons release more transmitter on the distal bundle than on the proximal bundle. The aim of our studies was to investigate the structural basis of this differentiation. Thin sections cut at 50 microns intervals showed a similar number of excitatory synapses on the two bundles. Freeze- fracture views of excitatory synapses showed that synapse size, active zone number per synapse, and intramembrane particle density in the postsynaptic membrane are similar proximally and distally. Active zones at synapses on the distal bundle are larger and contain about 50% more large intramembrane particles, which are thought to include the voltage- gated Ca2+ channels that couple the action potential to transmitter release, than their counterparts on the most proximal bundle. This difference in channel number appears to produce a disproportionate increase in the probability of transmitter release sufficient to account for most of the proximal-distal disparity in the amplitude of the excitatory postsynaptic potential. In contrast, staining the inhibitor for antibodies to the inhibitory neurotransmitter, GABA, showed that it forms more varicosities on the distal bundle than on the proximal bundle. Because most of the synapses are located in the varicosities, differences in synapse number likely regulate the proximal-distal disparity in the amount of inhibitory transmitter released. Therefore, the regional differentiation in the amount of transmitter released in the DAFM appears to be based on two distinct mechanisms. In the inhibitor, transmitter release appears to be regulated differentially by differences in synapse number. In the excitor, transmitter release appears to be regulated differentially from a similar number of synapses by differences in active zone structure.
Selection of alternative G-mediated signaling pathways at the dopamine D2 receptor by protein kinase C
Authors: Di Marzo V , Vial D , Sokoloff P , Schwartz JC , Piomelli D
Published: March 2018

Evidence indicates that a single membrane receptor subtype may be responsible for the generation of multiple intracellular signals, but mechanisms allowing for the selection of a specific effector pathway have not yet been documented. In neurons and other cells, the stimulation of dopamine D2 receptors produces, via G-protein activation, a spectrum of intracellular responses including inhibition of adenylyl cyclase activity, modulation of K+ currents, and potentiation of Ca(2+)-evoked arachidonic acid (AA) release. In this study, we report that, in Chinese hamster ovary cells, stimulation of protein kinase C (PKC) directs the preferential coupling of transfected D2 receptors from inhibition of adenylyl cyclase to potentiation of AA release, two responses mediated by Gi. The switch between these two signaling systems is accompanied by marked changes in their GTP sensitivities, indicating that it may result from the phosphorylation of component(s) of the receptor-Gi-protein complex. Brain PKC activity is enhanced by neurotransmitters and by neuronal depolarization. Thus, the ability of this protein kinase to remodel signaling pathways at the D2 receptor may regulate these Gi-mediated responses in an activity- dependent manner, and represent a novel form of synaptic plasticity.
Reversible heat stress-related loss of phosphorylated Alzheimer-type epitopes in Tau proteins of human neuroblastoma cells
Authors: Chiang MF , Liu WK , Yen SH
Published: March 2018

Human neuroblastoma cells, LAN, were used to study the phosphorylation and dephosphorylation of tau proteins. These cells contained mainly a form of tau comparable to fetal brain tau in molecular weight (55 kDa). Neuroblastoma tau reacted with antibodies that recognize epitopes spanning the whole tau molecule (E-1, Alz50, Tau-1, and Tau46), and antibodies (PHF-1, NP8, and T3P) that recognize hyperphosphorylated tau (PHF-tau) in Alzheimer's disease (AD) brains. Exposure of the cells to 45 degrees C heat stress resulted in dephosphorylation of the epitopes recognized by PHF-1, NP8, and T3P. Transfer of the heat-stressed cells to 37 degrees C led to rephosphorylation of the dephosphorylated epitopes. Cells that had been treated with okadaic acid (OA), regardless of whether they were subsequently subjected to heat stress or heat stress and recovery, all contained tau with a molecular weight similar to that of control cells. These tau proteins, similar to tau in control cells, also reacted with antibodies to phosphorylated epitopes. However, unlike the tau from control or heat-stressed cells, the OA- treated and heat-stressed tau had decreased reactivity with Tau-1. Alteration of Tau-1 immunoreactivity has been reported to be an early event in AD neurodegeneration. The reduction of Tau-1 immunoreactivity observed in OA-treated samples could be restored by incubation of electroblots of isolated tau with alkaline phosphatase, indicating an induction of the Tau-1 epitope phosphorylation by OA.(ABSTRACT TRUNCATED AT 250 WORDS)
Identification and characterization of Drosophila genes for synaptic vesicle proteins
Authors: DiAntonio A , Burgess RW , Chin AC , Deitcher DL , Scheller RH , Schwarz TL
Published: March 2018

Proteins associated with synaptic vesicles are likely to control the release of neurotransmitter. Because synaptic transmission is fundamentally similar between vertebrates and invertebrates, vesicle proteins from vertebrates that are important for synaptic transmission should be present in Drosophila as well. This investigation describes Drosophila homologs of vamp, synaptotagmin, and rab3 that are expressed in a pattern consistent with a function in Drosophila neurotransmission. One previously reported candidate (syb), a Drosophila homolog of the vamp or synaptobrevin proteins, has been shown to be expressed at very low levels in neurons and is most abundant in the gut. A neuronal Drosophila vamp (n-syb) is described here and is localized to chromosome band 62A. Northern analysis and in situ hybridizations to mRNA indicate that the novel vamp, as well as the genes for synaptotagmin (syt) and rab3 (drab3), is expressed in the Drosophila nervous system. These genes are widely (perhaps ubiquitously) expressed in the nervous system and we have no evidence of additional neuronal isoforms of synaptotagmin, vamp, or rab3. Immunoreactivity for synaptotagmin and vamp is located in synaptic regions of the nervous system. This distribution suggests that these molecules are components of synaptic vesicles in Drosophila. The conserved structure and neuronal expression pattern of these genes indicate that they may function in processes that are required for both vertebrate and invertebrate synaptic transmission. Because of their distribution in the nervous system and because n-syb, synaptotagmin, and drab3 do not appear to be in a family of functionally redundant homologs, we predict that mutation of these genes will have a profound neurological phenotype and that they are therefore good candidates for a genetic dissection in Drosophila.
Serotonin activation of a cyclic AMP-dependent sodium current in an identified neuron from Helisoma trivolvis
Authors: Price CJ , Goldberg JI
Published: March 2018

The mechanisms by which neurotransmitters regulate neurite extension and growth cone motility have been extensively studied using identified Helisoma neurons regenerating in cell culture. Specific neurons, such as buccal neuron B19, display a complex response to the addition of 5- HT involving the generation of action potentials, influx of extracellular calcium, and cessation of neurite extension and growth cone motility. While several studies have addressed the role of calcium in this cascade, little is known about the mechanism underlying the 5- HT-induced excitation of neuron B19. Therefore, we have begun to characterize the ion currents, receptors, and second messengers involved in the 5-HT-dependent depolarization of B19. Exposure of B19 to 5-HT resulted in the activation of a maintained inward current. Ion substitution experiments revealed that this current was carried mainly by sodium ions. The use of 8-bromo-cAMP, forskolin, or the phosphodiesterase inhibitor isobutyl methylxanthine (IBMX) to increase intracellular cAMP levels all resulted in inward current activation in the absence of 5-HT. Moreover, preloading the neuron with 8-bromo-cAMP was sufficient to prevent further current activation by 5-HT. In addition, the IBMX-activated current was greatly enhanced when induced in the presence of 5-HT. Protein kinase inhibitors failed to prevent 5- HT activation of sodium current, suggesting that cAMP may directly activate the current, independent of phosphorylation. Pharmacological experiments showed the B19 5-HT receptor has an EC50 of approximately 10(-7) M and can be activated by various indole analogs of 5-HT. Furthermore, methysergide displayed partial agonist activity.(ABSTRACT TRUNCATED AT 250 WORDS)
Identification of Proteins Required for Precise Positioning of Apc2 in Dendrites
Authors: Weiner Alexis T , Seebold Dylan Y , Michael Nick L , Guignet Michelle , Feng Chengye , Follick Brandon , Yusko Brandon A , Wasilko Nathan P , Torres-Gutierrez Pedro , Rolls Melissa M
Published: March 2018

In Drosophila neurons, uniform minus-end-out polarity in dendrites is maintained in part by kinesin-2-mediated steering of growing microtubules at branch points. Apc links the kinesin motor to growing microtubule plus ends and Apc2 recruits Apc to branch points where it functions. Because Apc2 acts to concentrate other steering proteins to branch points, we wished to understand how Apc2 is targeted. From an initial broad candidate RNAi screen, we found Miro (a mitochondrial transport protein), Ank2, Axin, spastin and Rac1 were required to position Apc2-GFP at dendrite branch points. YFP-Ank2-L8, Axin-GFP and mitochondria also localized to branch points suggesting the screen identified relevant proteins. By performing secondary screens, we found that energy production by mitochondria was key for Apc2-GFP positioning and spastin acted upstream of mitochondria. Ank2 seems to act independently from other players, except its membrane partner, Neuroglian (Nrg). Rac1 likely acts through Arp2/3 to generate branched actin to help recruit Apc2-GFP. Axin can function in a variety of wnt signaling pathways, one of which includes heterotrimeric G proteins and Frizzleds. Knockdown of Gαs, Gαo, Fz and Fz2, reduced targeting of Apc2 and Axin to branch points. Overall our data suggest that mitochondrial energy production, Nrg/Ank2, branched actin generated by Arp2/3 and Fz/G proteins/Axin function as four modules that control localization of the microtubule regulator Apc2 to its site of action in dendrite branch points.
How Do Stakeholder Groups’ Views Vary on Technology in Language Learning?
Authors: Trace Jonathan , Brown James Dean , Rodriguez Julio
Published: March 2018

This study examines how technology is perceived by different stakeholder groups in The Language Flagship programs. We administered questionnaires to three stakeholder groups: 14 directors, 34 instructors, and 100 learners at a variety of institutions with three goals: (a) to investigate what technologies the directors, instructors, and learners find useful for language instruction; (b) to explore how and to what degree the perceptions of the directors, instructors, and learners agree about technologies they think use; and (c) to study how learners’ views vary with regard to the value of various technologies for language learning inside and outside the classroom.
Petrol and Natural Gas Market of the Visegrád Group Countries 1993–2016: Current State and Prospects
Authors:   Pedagogical University of Kraków (Poland), Kłaczyński Robert
Published: March 2018

The paper addresses problems related to energy policies pursued by Central European countries. It identifies the amounts of energy resources in individual countries in the Visegrád Group as well as the transmission infrastructures they use for natural gas and crude oil. The author discusses projects aimed at diversifying energy supplies which are of key importance to V4 countries. The article also presents relations between those countries in both within the group and bilaterally. When outlining prospects of a V4 energy strategy, the account is taken of such vital aspects as relations with the Russian Federation and the contribution made by Visegrád countries to EU actions designed to develop a single energy market.
Transitional Justice in Relationship to Public Sphere and Civil Society: Theoretical Approaches
Authors:   Łódź University of Technology (Poland), Pietrzak Edyta
Published: March 2018

The article presents the entitled fields in the framework of their mutual influence. The notion of the public sphere is valuable for understanding the role that civil society plays in transitional justice processes. However transitional justice often reduces the idea of civil society to NGOs and ignores the social movements and civic engagement in the public realm that can be perceived as integral to the creation of new cases for understanding justice in transition. This fact results in the lack of perception of the civil society place in transitional justice processes. Thus the presented paper is based on hermeneutics, critical discourse analysis and dialogue between various theoretical approaches.
Post-Transplant Natural Antibodies Associate with Kidney Allograft Injury and Reduced Long-Term Survival
Authors: See Sarah B. , Aubert Olivier , Loupy Alexandre , Veras Yokarla , Lebreton Xavier , Gao Baoshan , Legendre Christophe , Anglicheau Dany , Zorn Emmanuel
Published: March 2018

Background The development of antibodies specific to HLA expressed on donor tissue (donor-specific antibodies [DSAs]) is a prominent risk factor for kidney graft loss. Non-HLA antibodies with pathogenic potential have also been described, including natural antibodies (Nabs). These IgG Nabs bind to immunogenic self-determinants, including oxidation-related antigens.

Methods To examine the relationship of Nabs with graft outcomes, we assessed Nabs in blinded serum specimens collected from a retrospective cohort of 635 patients who received a transplant between 2005 and 2010 at Necker Hospital in Paris, France. Serum samples were obtained immediately before transplant and at the time of biopsy-proven rejection within the first year or 1 year after transplant. Nabs were detected by ELISA through reactivity to the generic oxidized epitope malondialdehyde.

Results Univariate Cox regression analysis identified the development of post-transplant Nabs (defined as 50% increase in reactivity to malondialdehyde) as a significant risk factor for graft loss (hazard ratio, 2.68; 95% confidence interval, 1.49 to 4.82; P=0.001). Post-transplant Nabs also correlated with increased mean Banff scores for histologic signs of graft injury in post-transplant biopsy specimens. Multivariable Cox analyses confirmed Nabs development as a risk factor independent from anti-HLA DSAs (hazard ratio, 2.07; 95% confidence interval, 1.03 to 4.17; P=0.04). Moreover, patients with Nabs and DSAs had a further increased risk of kidney graft loss.

Conclusions These findings reveal an association between Nabs, kidney graft injury, and eventual graft failure, suggesting the involvement of Nabs in immune mechanisms of rejection.
İŞGÖRENLERİN DIŞSAL PRESTİJ VE ÖRGÜTSEL DESTEK ALGISININ POZİTİF ÖRGÜTSEL ÇIKTILAR ÜZERİNDEKİ ETKİSİ: BUTİK OTEL İŞLETMELERİNDE BİR ARAŞTIRMA
Authors: AYDOĞAN Enver , DENİZ Gaye
Published: March 2018

Bu
çalışmada, işgörenlerin dışsal prestij ve örgütsel destek algısının pozitif
örgütsel çıktılar olan iş tatmini, örgütsel özdeşleşme ve örgütsel vatandaşlık
davranışı üzerindeki etkisi araştırılmıştır. Araştırmada kullanılan veriler,
Kapadokya bölgesinde yer alan, misafirlerine “evinde gibilik” duygusu yaşatan
ve “kişiye özel” hizmet sunan, Kültür ve Turizm Bakanlığı’ndan “Turizm İşletme
Belgeli Özel Tesis” statüsüne sahip, ulusal ya da uluslararası anlamda
prestijli ödül sahibi ve 30 oda ve üstü kapasiteye sahip butik otel
işletmelerinde çalışan 223 işgörene anket uygulanması ile elde edilmiştir.
Araştırma sonuçlarına göre; hem algılanan dışsal prestijin hem de algılanan
örgütsel desteğin, iş tatminini, örgütsel özdeşleşmeyi, örgütsel vatandaşlık
davranışı ile örgütsel vatandaşlık davranışının boyutlarını olumlu yönde ve
anlamlı bir şekilde etkilediği ortaya konmuştur.
miRNA mimic transfection with Lipofectamine RNAiMAX v1
Authors: Bisagni Alessandra , Croci Stefania
Published: March 2018

This protocol is provided for optimization of miRNA mimics transfection in a 6-well plate. Lipofectamine® RNAiMAX Transfection Reagent is a proprietary formulation for transfecting small RNAs (e.g., siRNA, Silencer® Select siRNA, Stealth® RNAi, mirVana™ miRNA mimics and inhibitors) into a wide range of eukaryotic cells.
Respiratory picornavirus genotyping conventional nested RT-PCR ("Wisdom VP42 assay") v1
Authors: M Mackay Ian , Y. T. Wang Claire , E Arden Katherine
Published: March 2018

This is my preferred, previously published [Ref 1], rhinovirus (RV) and enterovirus (EV) genotypingassay when seeking to characterize the genotypes of respiratory picornavirus identified after use of a screeningreal-timeRT-PCR to test nucleic acid extracts fromclinicalsamples. I have not confirmedthat it can detectevery single RV genotype but I do know that it detectsmanyfrom each of the threeRV species (Human rhinovirus A,Human rhinovirus BandHuman rhinovirus C) as well as at least someHuman enterovirus(EV) genotypes. The assay picks up EVs due to the shared genetic similarities inthe5'UTR target region. EVs can be discriminatedusing subgenomic sequencing (see VP42 typing assay protocol), or simply described as 'respiratory EVs' since there is no specific-specific vaccine ortreatment available anyway. This is arobust primary subgenomic sequencing assay. It is more sensitive than any VP1 protocols because it targets more conserved primer target sites. It produces a more reliabletyping result than does the 5'UTR region alone.
The Civil Society Dynamic of Including and Empowering Refugees in Canada’s Urban Centres
Authors: Schmidtke Oliver
Published: March 2018

This article addresses the critical role that civil society at the urban level plays in integrating and empowering immigrants and minorities in Canadian society. From a place-based approach, it investigates how key agencies in the local community have been instrumental in including immigrants in general and refugees in particular into the fabric of Canadian society. Empirically the analysis focuses on Neighbourhood Houses in Greater Vancouver and the Privately-Sponsored Refugee program in Canada. With the interpretative lens on the urban context, the article shows how immigrants and refugees have gained agency and voice in the public arena through place-based communities. The insight into these two empirical cases provides the basis for conceptualizing the socio-political dynamics of immigrant settlement and integration in terms of the effects generated by urban governance structures.
All Work and No Play? Facilitating Serious Games and Gamified Applications in Participatory Urban Planning and Governance
Authors: Ampatzidou Cristina , Gugerell Katharina , Constantinescu Teodora , Devisch Oswald , Jauschneg Martina , Berger Martin
Published: March 2018

As games and gamified applications gain prominence in the academic debate on participatory practices, it is worth examining whether the application of such tools in the daily planning practice could be beneficial. This study identifies a research–practice gap in the current state of participatory urban planning practices in three European cities. Planners and policymakers acknowledge the benefits of employing such tools to illustrate complex urban issues, evoke social learning, and make participation more accessible. However, a series of impediments relating to planners’ inexperience with participatory methods, resource constraints, and sceptical adult audiences, limits the broader application of games and gamified applications within participatory urban planning practices. Games and gamified applications could become more widely employed within participatory planning processes when process facilitators become better educated and better able to judge the situations in which such tools could be implemented as part of the planning process, and if such applications are simple and useful, and if their development process is based on co-creation with the participating publics.
Mosquito (Diptera; Culicidae) of Pyriatyn district
Authors: Kilochytska N. , Stetsenko O.
Published: March 2018

The research of the species diversity and ecological features of mosquitoes is an important stage in the development of insects' quantity control methods. The areas with low anthropogenic influence, among which a particular place is given to the special nature reserve areas, may serve as a model for this kind of studies. Until now, neither the species composition of mosquitoes from Pyryatin district nor the special features of their development and dispersal were not investigated, that establishes an academic and practical relevance of the current work.
The aim of this investigation was to determine the species composition of mosquitoes, to make an analysis of the groups structure and to determine ecological features of adults that belong to common bloodsucking species. Research material of the years 2014-2015 was collected from Pyryatin district, which includes the National Park (NNP) "Pyryatinskyi." Gathering and collection of material were performed by conventional methods.
The 20 species and subspecies of 5 mosquito generas – Anopheles, Coguillettidia, Aëdes, Ochlerotatus, and Culex were registered in the Pyryatyn district. Aëdes cinereus (dominance index: Di – 34%), Culex modestus (Di – 18%) and Aëdes vexans (Di – 16%) appeared to be mass species. According to given environmental characteristics, these mosquitoes are anthropophilous, eurygamous, eurytopic and mostly exophilic bloodsuckers. Aë. vexans in residential areas has shown itself to be an exophilic and endophilic bloodsucker. These types under certain circumstances may pose a potential epidemic danger.
Phylogenetic analysis of see-transmitted isolate of Zucchini yellow mosaic virus
Authors: Tymchyshyn O. , Kosenko I. , Shevchenko T. Shevchenko , Shevchenko O. , Budzanivska I.
Published: March 2018

Zucchini yellow mosaic virus (ZYMV) remains one of the most widespread and destructive viruses affecting plants from Cucurbitaceae family in Ukraine as well as in other countries. ZYMV during the early stages of plant development can cause significant losses in yield. In current project the possibility of seed transmission of Ukrainian ZYMV isolates was tested on Cucurbita pepo plants in insect-free greenhouse. The rate was assessed by ELISA and RT-PCR. Only one isolate ZYMV-14P showed seedborne transmission with transmission rate 2,6%. This is the first detected seed-transmitted isolate in Ukraine. Phylogenetic analysis defined ZYMV-14P isolate as member of group A. This isolate was clustered with other known Ukrainian isolates and isolates from Hungary, Czech Republic, Austria and France within subgroup AI.
Предчувствие антропологической катастрофы в «Записках сумасшедшего» Н. В. Гоголя
Authors: Матонин Василий Николаевич , Бедина Наталья Николаевна , Егорова Екатерина Николаевна
Published: March 2018

Повесть русского писателя Н. В. Гоголя «Записки сумасшедшего» (1834) — одно из наиболее известных философских сочинений автора. Произведение Н. В. Гоголя осмысливается в контексте диалоговой концепции культуры М. М. Бахтина, которая предполагает возможность «превосхождения» текстом своего автора, а также возможность гениальных авторских прозрений.

В образе героя повести Аксентия Ивановича Поприщина находит отражение предчувствие «антропологической катастрофы» (М. Мамардашвили). Ее признаки Гоголь удивительно точно воплотил в художественном образе гораздо раньше, чем она была осмыслена с помощью категориального аппарата философии. Чем дальше читатель погружается в сознание героя, тем очевиднее для него становится онтологическое одиночество человека, воплощенное в безумии «брошенного в мир» (М. Хайдеггер) героя. В поисках выхода за пределы ограниченности, конечности человека Гоголь идет тем же путем, который обозначит Э. Кассирер, оппонирующий М. Хайдеггеру, — в осмысленное бытие культурных форм. Предчувствуя опасность антропологической катастрофы, Гоголь через своего героя предлагает человеку найти основания для собственного существования в жертвенном служении и в молитве (вере). В мире иллюзий (в «безумии от недумания») жертва, страдание — путь возвращения к реальности, невозможный без чувства Родины. В этом смысле актуальным оказывается вопрос о национальном характере прозы Гоголя.

В языке и образном строе произведения писатель находит способ показать универсальное в национальном, так как подлинный патриотизм предполагает интуитивное стремление к универсализму, к преодолению национальной замкнутости и ограниченности.
«Горизонты гуманитарного знания»
Authors: Луков Валерий Андреевич , Луков Сергей Валерьевич
Published: March 2018

В статье представлен электронный журнал «Горизонты гуманитарного знания», выходящий на базе Московского гуманитарного университета и направленный на расширение круга гуманитариев в России. Журнал продолжает традиции издания информационного гуманитарного портала «Знание. Понимание, Умение», а также вносит новое в понимание особой роли гуманитаристики в современном мире.
Some clinical morphological and molecular genetic aspects in patients with clinical signs of hereditary breast cancer
Authors: Shatova Yu S , Chebotareva E A , Zlatnik E Yu , Novikova I A , Vodolazhskiy D I , Dzhenkova E A
Published: March 2018

Aim. To study the clinical morphological and molecular genetic characteristics of clinically hereditary breast cancer with and without verified mutation of BRCA1, BRCA2 compared to sporadic breast cancer.

Methods. The study included 191 female patients with verified breast cancer stage I-IIA and clinical signs of hereditary breast cancer. In order to identify mutations in genes ВRCA1/2 molecular genetic analysis of deoxyribonucleic acid from peripheral blood leukocytes was performed.

Results. The total frequency of mutations in the genes BRCA1 and ВRCA2 amounted 14.1% of the total number of examined patients. The most common mutation in clinically hereditary breast cancer among residents of the Rostov Region was 5382insC in BRCA1 gene, which corresponds to the nationwide data. Also common features of hereditary breast cancer compared to sporadic breast cancer were identified: young age at the time of disease manifestation, high prevalence of triple-negative cancer, history of infertility, increased level of p53 and androgen receptor expression, decreased level of aneuploid cell and proliferation index in the tumor.

Conclusion. In a number of clinical morphological and molecular genetic parameters, clinically hereditary breast cancer differs from sporadic breast cancer. These indicators in the future can be used as criteria for selection of patients with clinically hereditary breast cancer without confirmed BRCA1/2 mutation by standard panels for in-depth genetic testing.
Experimental purulent corneal ulcer in rabbits as a model to study ocular dosage forms
Authors: Ozhmukhametova E K , Mussin M N , Bayachmetov A , Adambosynov B , Khutoryanskiy V V
Published: March 2018

Aim. The aim of this work was to develop experimental model of purulent corneal ulcer in rabbits for its application in the studies of ocular dosage forms.

Methods. Rabbits body temperature was measured in three groups: (1) without corneal injury; (2) with the injury and formation of purulent ulcer, but without any therapy; (3) with the injury and formation of purulent ulcer, treated with ciprofloxacin. In parallel, swabs containing purulent discharge were taken for microbiological analysis. In the end of 10-days experiment rabbits (groups 2 and 3) were sacrificed; their corneas were extracted and analysed.

Results. One day following the injury all rabbits had a purulent discharge, moderate eyelids edema and conjunctival hyperemia. Rabbits in groups 2 and 3 had a purulent corneal ulcer developed. The mean body temperature in group 1 was 38.6±0.1 °С; in group 2 it was 40.0±0.3 °С, in group 3 it was 39.1±0.3 °С. The levels of infection in group 2 in the beginning and on 10-th day of experiments were 1.0×107 colony forming units (CFU) and 4.3×106 CFU, respectively (not significant, p >0.1). In group 3 these levels were 1.0×107 CFU and 4.6×103 CFU, respectively (significant, p <0.0001). The histological investigation of enucleated eyes with corneal ulcers revealed the presence of edema, stratification, deep epithelial defects, endothelium desquamation, and corneal infiltration by neutrophils.

Conclusion. Formation of a corneal ulcer leads to an increase in animal body temperature, which depends on timely therapy. Rectal temperature measurements in rabbits could serve as an easy parameter to follow the development of inflammation.
Sudden cardiac death as an onset of myocardial infarction
Authors: Sadykov M N , Frolova E B , Tsibul'kin N A , Akhmetzyanova E F , Aynutdinova I A , Mingazetdinov M A , Aglullina E I , Yagudina E N
Published: March 2018

Sudden cardiac death is an actual problem of current cardiology. Ventricular arrhythmias are considered the main mechanism of its development: ventricular fibrillation and flutter, sustained ventricular tachycardia and asystoly. Pathological changes of electrophysiologic processes in myocardium and conducting system of ventricles are the reasons of arrhythmia development. Coronary heart disease is considered the most frequent etiological factor of sudden cardiac death. Acute ischemia in the onset of myocardial infarction can be the cause of fatal arrhythmias leading to sudden cardiac death. Well-timed cardiopulmonary resuscitation and cardioversion allow restoring the heart activity. The article presents short review of scientific medical literature on the subject of sudden cardiac death in myocardial infarction. The clinical value of this pathology is illustrated with an example from practice - a case of the onset of acute myocardial infarction in the form of sudden cardiac death.
Clinical justification for preventive surgeries for abdominal wall hernias and cholelithiasis in cardiovascular surgical patients
Authors: Sangadzhiev S B , Slavin L E , Zimagulov R T , Yakhin R R , Sangadzhiev M S , Slavina A L , Podshivalov A G , Gaynanov M A
Published: March 2018

Aim. Clinical justification for the necessity of sanitation surgeries for cholelithiasis and abdominal wall hernias in patients intended for heart valve surgery.

Methods. The study is based on the analysis of operative treatment results of 54 patients admitted to surgical department of Interregional clinical diagnostic center (Kazan) in 2007-2017 with cholelithiasis and abdominal wall hernias, who underwent laparoscopic cholecystectomy or herniotomy before or after an open heart surgery in cardiac surgical department No. 2 of the hospital. All patients were divided into two clinical groups. Group 1 consisted of 36 patients with a history of prosthetic heart valve, taking long-term warfarin. The comparison group included 18 patients, who at the first stage before cardiac surgery underwent sanitation surgeries for cholelithiasis and/or abdominal wall hernias. As part of the research, statistical analysis of intergroup differences was performed using non-parametric Mann-Whitney U-tests. Intergroup differences were determined by gender, age and type of cardiac and general surgical pathology.

Results. The analysis of the study groups showed that the average hospital stay among patients with long-term use of indirect anticoagulants was 15±1 day and varied from 12 to 19 days. The results indicate more than two-fold increase of an average hospital stay compared to patients, who underwent the same surgeries before cardiac interventions (р <0.05).

Conclusion. Before performing cardiac valve replacement with planned life-term or long-term use of anticoagulants with concomitant general surgical pathology (cholelithiasis, abdominal wall hernias with a tendency to strangulate), at the first stage, it is reasonable to perform so called sanitation surgeries aimed at eliminating abdominal pathology; such approach significantly decreases hospital stay of patients, and potentially contributes to lower probability of hemorrhagic complication incidences during the surgery and in the early post-operative period.