bluuebunny/crossref_metadata_2025 huggingface dataset:
Recombinant swine beta interferon protects swine alveolar macrophages and MARC-145 cells from infection with Porcine reproductive and respiratory syndrome virus
Authors: Overend C. , Mitchell R. , He D. , Rompato G. , Grubman M. J. , Garmendia A. E.
Published: February 2007

Swine beta interferon (swIFN-β) produced in HEK 293 cells infected with a recombinant, replication-defective human adenovirus 5 (Ad5) encoding the swIFN-β gene was tested for antiviral activity against Porcine reproductive and respiratory syndrome virus (PRRSV). MARC-145 cells were incubated overnight with dilutions of supernatant fluids from HEK 293 cells infected with Ad5-swIFN-β or with an Ad5 control virus (Ad5-Blue). Treated cells were infected with PRRSV; MARC-145 cells incubated with Ad5-Blue supernatants developed cytopathic effects (CPE), whereas those incubated with swIFN-β showed no CPE. To confirm the antiviral activity of swIFN-β, culture fluids from Ad5-swIFN-β-infected cells were affinity-purified on a Sepharose–anti-swIFN-β matrix, and the resulting fractions exhibited antiviral activity upon infection with PRRSV. The antiviral effects were specific, as they were blocked by mAbs against swIFN-β. Additional cultures of MARC-145 cells treated with swIFN-β-containing supernatants or affinity-purified swIFN-β were infected with PRRSV and tested by real-time RT-PCR for viral RNA in culture supernatants at various times post-inoculation. These experiments confirmed the protective effects of swIFN-β. swIFN-β was also tested for antiviral activity on porcine alveolar macrophages (PAMs) obtained by bronchoalveolar lavage from PRRSV-negative swine. PAMs were treated with dilutions of swIFN-β or Ad5-Blue culture fluids, infected with PRRSV and tested for viral RNA by real-time RT-PCR. The viral load data showed a dose-dependent protection in swIFN-β-treated PAMs, whereas no protection was evident from Ad5-Blue culture fluids. The data demonstrate that swIFN-β protects both MARC-145 cells and PAMs from PRRSV infection.
Bacteriophage P4 sut1: a mutation suppressing transcription termination
Authors: Terzano Susanna , Oliva Ilaria , Forti Francesca , Sala Claudia , Magnoni Francesca , Dehò Gianni , Ghisotti Daniela
Published: February 2007

In the Escherichia coli satellite phage P4, transcription starting from PLE is prevalently controlled via premature termination at several termination sites. We identified a spontaneous mutation, P4 sut1 (suppression of termination), in the natural stop codon of P4 orf151 that, by elongating translation, suppresses transcription termination at the downstream t151
site. Both the translational and the transcriptional profile of P4 sut1 differed from those of P4 wild-type. First of all, P4 sut1 did not express Orf151, but a higher molecular mass protein, compatible with the 303 codon open reading frame generated by the fusion of orf151, cnr and the intervening 138 nt. Moreover, after infection of E. coli, the mutant expressed a very low amount of the 1.3 and 1.7 kb transcripts originating at PLE and PLL promoters, respectively, and terminating at the intracistronic t151
site, whereas correspondingly higher amounts of the 4.1 and 4.5 kb RNAs arising from the same promoters and covering the entire operon were detected. Thus the sut1 mutation converts a natural stop codon into a sense codon, suppresses a natural intracistronic termination site and leads to overexpression of the downstream cnr and α genes. This correlates with the inability of P4 sut1 to propagate in the plasmid state. By cloning different P4 DNA fragments, we mapped the t151
transcription termination site within the 7633–7361 region between orf151 and gene cnr. A potential stem–loop structure, resembling the structure of a Rho-independent termination site, was predicted by mfold sequence analysis at 7414–7385.
Synergistic pathogenicity of a phloem-limited begomovirus and tobamoviruses, despite negative interference
Authors: Pohl Diana , Wege Christina
Published: February 2007

In contrast to previous observations on phloem-limited geminiviruses supported in movement andaccumulation by RNA viruses such as cucumo- and tobamoviruses, tissue infiltration by Abutilon mosaic virus (AbMV) was enhanced by neither Tobacco mosaic virus nor Tomato mosaic virus (ToMV) in two different hosts, Nicotiana benthamiana and tomato. Both tobamoviruses exerted a negative effect on the DNA virus, resulting in a decrease in AbMV accumulation and significantly reduced infectivity in N. benthamiana. Despite these unexpected molecular observations, a striking synergistic enhancement in pathogenicity occurred with respectto stunting and necrosis. In situ hybridization revealed that this was not due to any alteration of tissue infiltration by AbMV, which also remained limited to the phloem in the mixed infections. Transgenically expressed ToMV 30K movement protein was not able to induce phloemescape of AbMV in tomato plants and did not lead to any obvious change in begomovirus symptomatology.
Brn-3a suppresses pseudorabies virus-induced cell death in sensory neurons
Authors: Geenen Kristin , Nauwynck Hans J. , De Regge Nick , Braeckmans Kevin , Favoreel Herman W.
Published: February 2007

Sensory neurons of the trigeminal ganglion (TG) are of crucial importance in the pathogenesis of many alphaherpesviruses, constituting major target cells for latency and reactivation events. We showed earlier that a subpopulation of porcine TG neurons, in contrast to other porcine cell types, is highly resistant to cell death induced by infection with the porcine alphaherpesvirus pseudorabies virus (PRV). Here, we report that expression of Brn-3a, a neuron-specific transcription factor implicated in cell survival of sensory neurons, correlates with the increased resistance of TG neurons towards PRV-induced cell death. In addition, overexpression of Brn-3a in the sensory neuronal cell line ND7 markedly increased resistance of these cells to PRV-induced cell death. Hence, Brn-3a may play a hitherto uncharacterized role in protection of sensory neurons from alphaherpesvirus-induced cell death, which may have implications for different aspects of the alphaherpesvirus life cycle, including latency/reactivation events.
A comparison of algorithms for the identification of specimens using DNA barcodes: examples from gymnosperms
Authors: Little Damon P. , Stevenson Dennis Wm.
Published: February 2007

In order to use DNA sequences for specimen identification (e.g., barcoding, fingerprinting) an algorithm to compare query sequences with a reference database is needed. Precision and accuracy of query sequence identification was estimated for hierarchical clustering (parsimony and neighbor joining), similarity methods (BLAST, BLAT and megaBLAST), combined clustering/similarity methods (BLAST/parsimony and BLAST/neighbor joining), diagnostic methods (DNA–BAR and DOME ID), and a new method (ATIM). We offer two novel alignment‐free algorithmic solutions (DOME ID and ATIM) to identify query sequences for the purposes of DNA barcoding. Publicly available gymnosperm nrITS 2 and plastid matK sequences were used as test data sets. On the test data sets, almost all of the methods were able to accurately identify sequences to genus; however, no method was able to accurately identify query sequences to species at a frequency that would be considered useful for routine specimen identification (42–71% unambiguously correct). Clustering methods performed the worst (perhaps due to alignment issues). Similarity methods, ATIM, DNA–BAR, and DOME ID all performed at approximately the same level. Given the relative precision of the algorithms (median = 67% unambiguous), the low accuracy of species‐level identification observed could be ascribed to the lack of correspondence between patterns of allelic similarity and species delimitations. Application of DNA barcoding to sequences of CITES listed cycads (Cycadopsida) provides an example of the potential application of DNA barcoding to enforcement of conservation laws.

© The Willi Hennig Society 2006.
Heterology: the shadows of a shade
Authors: Williams David M. , Ebach Malte C.
Published: February 2007

The recent proposition to name some similarities not due to common ancestry as examples of heterology is discussed from a historical point of view. The use of an elaborate terminology for various kinds of similarities is examined and rejected in favor of dealing with homology and non‐homology.

© The Willi Hennig Society 2006.
Propofol infusion for control of status epilepticus
Authors: MACKENZIE S. J. , KAPADIA F. , GRANT I. S.
Published: February 2007

Two patients with status epilepticus who were resistant to conventional treatment but responded to propofol infusions are reported. An electroencephalogram confirmed the seizures and their successful treatment.
Atlanto‐axial subluxation in Down's syndrome
Authors: POWELL J. F. , WOODCOCK T. , LUSCOMBE F. E.
Published: February 2007

A case of atlanto‐axial subluxation in a patient with Down's syndrome is described. The gradual deterioration in the patient's locomotor ability caused a delay in diagnosis. Patterns of presentation of this condition are discussed.
32‐gauge spinal catheters through 26‐gauge needles
Authors: NAGLE C. J. , McQUAY H. J. , GLYNN C. J.
Published: February 2007

Small diameter intrathecal catheters potentially combine the certainty of intrathecal injection and the advantage of repeatability, without the risk of a high incidence of headache after dural puncture. We report problems placing such catheters.
Pressure generated during insertion of lumbar epidurals. A comparison with the Portex epidural injection simulator
Authors: LANGTON J. A. , MEIKLEJOHN B. H.
Published: February 2007

The aim of this study was to measure pressures exerted during insertion of lumbar epidurals in obstetric patients. The pressures were compared with those obtained when the Portex epidural injection simulator was used, and were significantly greater when a saline technique was used compared to those when air was used (p < 0.05). There were no differences between the pressures obtained with the simulator and those measured in vivo.
The Ohmeda 9000 syringe pump The first of a new generation of syringe drivers
Authors: STOKES D. N. , PEACOCK J. E. , LEWIS R. , HUTTON P.
Published: February 2007

The Ohmeda 9000 syringe pump was developed in response to the need for an infusion apparatus to administer intravenous anaesthetic agents. It incorporates a bolus facility for the rapid, controlled delivery of loading infusions, or incremental dosing over a background maintenance infusion, and may be interfaced with a controller for computer‐driven infusions. The Ohmeda 9000 pump has undergone bench testing and detailed evaluation in clinical practice using a variety of syringe sizes and makes. It is capable of accurate delivery over a range of infusion rates provided the recommended manufacturers’ syringes are used with the appropriate pump setting. The pump was easy to use and reliable in clinical research and routine clinical practice. It should find its niche as the first genuinely ‘anaesthetist‐friendly’ infusion pump.
Nasal pulse oximetry overestimates oxygen saturation
Authors: ROSENBERG J. , PEDERSEN M. H.
Published: February 2007

Ten surgical patients were monitored with nasal and finger pulse oximetry (Nellcor N‐200) for five study periods with alternating mouth and nasal breathing and switching of cables and sensors. Nasal pulse oximetry was found to overestimate arterial oxygen saturation by 4.7 (SD 1.4%) (bias and precision).
Influence of allophane and organic matter contents on surface properties of Andosols
Authors: Bartoli F. , Poulenard A. J. , Schouller B. E.
Published: February 2007

The aim of this study was to use nitrogen gas adsorption to study the complex surface properties of a wide range of Andosol Ah and Bw horizons; N2 gas adsorption not only provides specific surface area, SSA, but it also yields complementary information about micropore volume and hydrophilic and/or hydrophobic surface properties. Total SSAs were positively related to micropore SSA which was, in its turn, positively interrelated to the dimensionless parameter C of the Brunauer‐Emmett‐Teller (BET) equation (micropore N2 filling) and microporous allophane content. The more allophanic the Andosol horizon sample, the larger were its total, micropore and mesopore SSAs. On the other hand, strong negative exponential relationships were obtained between either total or micropore or mesopore SSA and soil organic carbon content, with a SSA threshold at an organic carbon content of c. 8–10%, the SSAs being extremely small at larger organic carbon content values. Both SSABET and CBET decreased non‐linearly as a function of the organic C/allophane ratio, with either a SSABET or a CBET threshold at an organic C/allophane ratio value of 3–5, above which both SSABET and CBET were very small (mostly the aluandic Andosol Ah horizons). The more the soil allophanes are assumed to be coated, the more hydrophobic the soil surfaces become and the smaller both SSABET and CBET become; nitrogen gas has a permanent quadrupole moment and therefore acts as a polar probe when surfaces are sufficiently hydrophobic. The antagonistic roles played by allophanes and organic matter in both the SSAs and the values of the dimensionless parameter C in the BET equation were also highlighted by (i) multiple linear regressions between the SSAs and both allophane and organic carbon contents and (ii) principal‐component analysis of SSABET, CBET and soil constituent (allophane, ferrihydrite and organic C) contents.
Mechanism of insulin‐like growth factor I‐mediated proliferation of adult neural progenitor cells: role of Akt
Authors: Kalluri Haviryaji S. G. , Vemuganti Raghu , Dempsey Robert J.
Published: February 2007

Insulin‐like growth factor I (IGF‐I) is involved in the proliferation and differentiation of adult neural progenitor cells; however, the underlying mechanism is not clear. We analysed the involvement of the phosphatidylinositol 3‐kinase/Akt and MEK/extracellular signal‐regulated kinase (ERK) pathways in the IGF‐I‐mediated proliferation of rat neural progenitor cells. Stimulation of neural progenitor cells with IGF‐I enhanced the phosphorylation of Akt but not ERK. Cell proliferation assay demonstrated that 2‐(4‐morpholinyl)‐8‐phenyl‐4H‐1‐benzopyran‐4‐one (phosphoinositide 3‐kinase inhibitor) but not 1,4‐diamino‐2,3‐dicyano‐1,4‐bis(2‐aminophenylthio)‐butadiene (U0126) (ERK inhibitor) inhibited the IGF‐I‐induced survival of cells, whereas fibroblast growth factor 2 (FGF‐2) enhanced the IGF‐I‐mediated survival of cells. Consistent with the cell proliferation assay, 5′bromo‐2‐deoxy‐uridine incorporation studies established a negative role for IGF‐I in proliferation. However, FGF‐2 (ERK activator) in the presence of IGF‐I (Akt activator) increased the proliferation of cells. Accordingly, stimulation of the ERK pathway by FGF‐2 induced the expression of cyclin D1, which is essential for the entry of cells into cell cycle, and IGF‐I in the presence of FGF‐2 up‐regulated the expression of cyclin D1. IGF‐I in the absence or presence of FGF‐2 increased the phosphorylation of glycogen synthase kinase, thus supporting its role in the survival of neural progenitor cells. To further confirm the role of ERK activation in the proliferation, we cultured cells in FGF‐2 + IGF‐I‐containing medium in the presence and absence of U0126 (ERK inhibitor), and showed the inhibition of nestin expression in U0126‐treated cells. The decrease in the cyclin D1 content in conjunction with the inhibition of nestin expression by ERK inhibitor confirms the role of ERK in the proliferation of cells.
Impact of S100B on local field potential patterns in anesthetized and kainic acid‐induced seizure conditions in vivo
Authors: Sakatani Seiichi , Seto‐Ohshima Akiko , Itohara Shigeyoshi , Hirase Hajime
Published: February 2007

S100B is a calcium‐binding protein predominantly expressed in astrocytes. Previous studies using gene‐manipulated animals have suggested that the protein has a role in synaptic plasticity and learning. In order to assess the physiological roles of the protein in active neural circuitry, we recorded spontaneous neural activities from various layers of the neocortex and hippocampus in urethane‐anesthetized S100B knockout (KO) and wildtype (WT) control mice. Typical local field oscillation patterns including the slow (0.5–2 Hz) oscillations in the neocortex, theta (3–8 Hz) and sharp wave‐associated ripple (120–180 Hz) oscillations in the hippocampus were observed in both genotypes. Comparisons of the frequency, power and peak amplitude have shown that these oscillatory patterns were virtually indistinguishable between WT and KO. When seizure was induced by intraperitoneal injection of kainic acid, a difference between WT and KO appeared in the CA1 radiatum local field potential pattern, where seizure events were characterized by prominent appearance of hyper‐synchronous gamma band (30–80 Hz) activity. Although both genotypes developed seizures within 40 min, the gamma amplitude was significantly smaller during the development of seizures in KO mice. Our results suggest that deficiency of S100B does not have a profound impact on spontaneous neural activity in normal conditions. However, when neural activity was sufficiently raised, activation of S100B‐related pathways may take effect, resulting in modulation of neural activities.
MAPKs are key players in mediating cytokine release and cell death induced by unconjugated bilirubin in cultured rat cortical astrocytes
Authors: Fernandes Adelaide , Falcão Ana S. , Silva Rui F. M. , Brito Maria A. , Brites Dora
Published: February 2007

When activated by unconjugated bilirubin (UCB), astrocytes are important sources of inflammatory mediators such as TNF‐α, IL‐1β and IL‐6, which may contribute for the neurotoxicity observed during severe neonatal hyperbilirubinemia. In the present study, we have addressed the role of the mitogen‐activated protein kinases (MAPKs) p38, Jun N‐terminal kinase (JNK)1/2 and extracellular signal‐regulated kinase (ERK)1/2 pathways and their relation with the nuclear factor κB (NF‐κB) cascade in the signalling events involved in cytokine release and cell death caused by UCB in primary cultures of rat astrocytes. Stimulation of astrocytes with UCB in the presence of all the MAPK inhibitors prevented UCB‐induced release of TNF‐α and IL‐6, while IL‐1β secretion was only reduced by JNK1/2 and ERK1/2 inhibitors. In addition, activation of the NF‐κB transcription factor, needed for cytokine release by UCB‐stimulated astrocytes, was shown to be dependent on JNK1/2 and ERK1/2 phosphorylation. Moreover, all MAPK inhibitors prevented astroglial apoptosis triggered by UCB. Interestingly, UCB‐induced lactate dehydrogenase release was prevented by blockade of JNK1/2, ERK1/2 and NF‐κB cascades but enhanced by p38 inhibition. Taken together, our data demonstrate for the first time that MAPK transduction pathways are key players in the UCB‐induced inflammatory response and cell death in astrocytes, probably also involving NF‐κB modulation. These findings contribute to unraveling the complex mechanisms of astrocyte reactivity to UCB and may ultimately prove useful in the development of new therapeutic strategies to prevent nerve cell damage during acute bilirubin encephalopathy.
Axonal accumulation of synaptic markers in APP transgenic Drosophila depends on the NPTY motif and is paralleled by defects in synaptic plasticity
Authors: Rusu Patricia , Jansen Anna , Soba Peter , Kirsch Joachim , Löwer Alexander , Merdes Gunter , Kuan Yung‐Hui , Jung Anita , Beyreuther Konrad , Kjaerulff Ole , Kins Stefan
Published: February 2007

Alzheimer's disease (AD) is characterized by neurofibrillary tangles and extracellular plaques, which consist mainly of β‐amyloid derived from the β‐amyloid precursor protein (APP). An additional feature of AD is axonopathy, which might contribute to impairment of cognitive functions. Specifically, axonal transport defects have been reported in AD animal models, including mice and flies that overexpress APP and tau. Here we demonstrate that the APP‐induced traffic jam of vesicles in peripheral nerves of Drosophila melanogaster larvae depends on the four residues NPTY motif in the APP intracellular domain. Furthermore, heterologous expression of Fe65 and JIP1b, scaffolding proteins interacting with the NPTY motif, also perturb axonal transport. Together, these data indicate that JIP1b or Fe65 may be involved in the APP‐induced axonal transport defect. Moreover, we have characterized neurotransmission at the neuromuscular junction in transgenic larvae that express human APP. Consistent with the observation that these larvae do not show any obvious movement deficits, we found no changes in basal synaptic transmission. However, short‐term synaptic plasticity was affected by overexpression of APP. Together, our results show that overexpression of APP induces partial stalling of axonal transport vesicles, paralleled by abnormalities in synaptic plasticity, which may provide a functional link to the deterioration of cognitive functions observed in AD.
Lateralized activation of Cluster N in the brains of migratory songbirds
Authors: Liedvogel Miriam , Feenders Gesa , Wada Kazuhiro , Troje Nikolaus F. , Jarvis Erich D. , Mouritsen Henrik
Published: February 2007

Cluster N is a cluster of forebrain regions found in night‐migratory songbirds that shows high activation of activity‐dependent gene expression during night‐time vision. We have suggested that Cluster N may function as a specialized night‐vision area in night‐migratory birds and that it may be involved in processing light‐mediated magnetic compass information. Here, we investigated these ideas. We found a significant lateralized dominance of Cluster N activation in the right hemisphere of European robins (Erithacus rubecula). Activation predominantly originated from the contralateral (left) eye. Garden warblers (Sylvia borin) tested under different magnetic field conditions and under monochromatic red light did not show significant differences in Cluster N activation. In the fairly sedentary Sardinian warbler (Sylvia melanocephala), which belongs to the same phyolgenetic clade, Cluster N showed prominent activation levels, similar to that observed in garden warblers and European robins. Thus, it seems that Cluster N activation occurs at night in all species within predominantly migratory groups of birds, probably because such birds have the capability of switching between migratory and sedentary life styles. The activation studies suggest that although Cluster N is lateralized, as is the dependence on magnetic compass orientation, either Cluster N is not involved in magnetic processing or the magnetic modulations of the primary visual signal, forming the basis for the currently supported light‐dependent magnetic compass mechanism, are relatively small such that activity‐dependent gene expression changes are not sensitive enough to pick them up.
A novel neurotransmitter‐independent communication pathway between axons and glial cells
Authors: Hartl Sandra , Heil Jan E. , Hirsekorn Andrea , Lohr Christian
Published: February 2007

Recent studies have provided evidence that transmitters released by neurons can activate glial receptors and stimulate calcium signalling in glial cells. Glial calcium signalling, in turn, may affect neuronal performance such as long‐term changes in synaptic efficacy. Olfactory ensheathing cells (OECs) are a special glial cell type in vertebrates and insects and promote axon growth in the developing and mature nervous system. Physiological properties of OECs, however, have not been studied so far in detail. We measured changes in the calcium concentration in OECs of the moth Manduca sexta, in situ and in vivo. Electrical stimulation of olfactory receptor neurons in pupae or odour stimulation of receptor neurons in adults resulted in calcium transients in OECs. Olfactory receptor axons release acetylcholine; however, application of acetylcholine or other transmitters such as glutamate, GABA or nitric oxide did not induce calcium transients in OECs. Upon nerve stimulation, extracellular potassium rose by several millimolar as measured with potassium‐sensitive microelectrodes. When potassium in the perfusion saline was increased from 4 to 10 mm or higher, voltage‐dependent calcium transients in OECs that resembled stimulation‐induced calcium transients were evoked. Blocking neuronal potassium channels with TEA reduced both the stimulation‐induced increases in extracellular potassium and the calcium transients in OECs, whereas calcium transients in receptor axons were augmented. Our results show for the first time that accumulation of potassium, released by electrically active axons, is sufficient to evoke voltage‐dependent calcium influx into glial cells, whereas neurotransmitters appear not to be involved in this neuron–glia communication in Manduca.
Changes in activity of the striatum during formation of a motor habit
Authors: Tang Chengke , Pawlak Anthony P. , Prokopenko Volodymyr , West Mark O.
Published: February 2007

To examine experience‐dependent plasticity of striatal neurons during habit learning in awake, freely moving animals, single neurons in the dorsolateral striatum (54 neurons related specifically to vertical head movement and 14 unresponsive neurons, i.e. not related to any body movement) were recorded and tracked off‐line to assess changes in firing rate over sessions as performance of instrumental head movement became automatic and habitual. Rats were trained to emit operant vertical head movements that triggered water delivery for 14 sessions (2 h per session, one session per day). Rats significantly increased the number and efficiency of head movements over sessions until reaching asymptotic behaviour. Habit formation was indicated by significantly higher levels of instrumental responding exhibited by rats during a late, relative to an early, session in which the reward was devalued. As head movements became habitual across sessions, most head movement‐related neurons (89%) exhibited decreased firing rate, while a small population (11%) exhibited increased or maintained firing rate. The rate of decrease in firing by the majority correlated with the rate of improvement in movement efficiency over sessions. All unresponsive neurons, though not apparently related to movement, exhibited decreased firing rate over sessions. Our findings suggest that, during habit learning, the striatum may shift from facilitating acquisition of efficient movement with a large population of neurons to modulating or maintaining habitual movement with stronger firing of fewer movement‐related neurons.
The involvement of primary motor cortex in mental rotation revealed by transcranial magnetic stimulation
Authors: Eisenegger C. , Herwig U. , Jäncke L.
Published: February 2007

We used single‐pulse transcranial magnetic stimulation of the left primary hand motor cortex and motor evoked potentials of the contralateral right abductor pollicis brevis to probe motor cortex excitability during a standard mental rotation task. Based on previous findings we tested the following hypotheses. (i) Is the hand motor cortex activated more strongly during mental rotation than during reading aloud or reading silently? The latter tasks have been shown to increase motor cortex excitability substantially in recent studies. (ii) Is the recruitment of the motor cortex for mental rotation specific for the judgement of rotated but not for nonrotated Shepard & Metzler figures? Surprisingly, motor cortex activation was higher during mental rotation than during verbal tasks. Moreover, we found strong motor cortex excitability during the mental rotation task but significantly weaker excitability during judgements of nonrotated figures. Hence, this study shows that the primary hand motor area is generally involved in mental rotation processes. These findings are discussed in the context of current theories of mental rotation, and a likely mechanism for the global excitability increase in the primary motor cortex during mental rotation is proposed.
Regulation of the subthreshold chloride conductance in the rat sympathetic neuron
Authors: Sacchi Oscar , Rossi Maria Lisa , Canella Rita , Fesce Riccardo
Published: February 2007

The mechanisms that control chloride conductance (gCl) in the rat sympathetic neuron have been studied by the two‐electrode voltage‐clamp technique in mature, intact superior cervical ganglia in vitro. In addition to voltage dependence in the membrane potential range −120/−50 mV, gCl displays time‐ and activity‐dependent regulation (sensitization). The resting membrane potential is governed by voltage‐dependent gK and gCl, which determine values of cell input conductance ranging from 7 to 18 nS (full deactivation) to an upper value of about 130 nS (full activation and maximal gCl sensitization). The quiescent neuron, held at constant membrane potential, spontaneously and gradually moved from a low‐ to a high‐conductance status. An increase (about 40 nS) in gCl accounted for this phenomenon, which could be prevented by imposing intermittent hyperpolarizing episodes. Following spike firing, gCl increased by 20–33 nS, independent of the cell conductance value preceding tetanization, and thereafter decayed to the pre‐stimulus level within 5 min. Intracellular sodium depletion and its successive ionophoretic restoration moved the neuron from a stable low‐conductance state to maximum gCl sensitization, pointing to a link between gCl sensitization and [Na+]i. The dependence of gCl build‐up on [Na+]i and the time‐course of such Na+‐related modulation have been examined: gCl sensitization was absent at 0 [Na+]i, was well developed (20 nS) at 15 mm and tended towards a saturating value of 60 nS for higher [Na+]i. Sensitization was transient in response to neuron activity. In the silent neuron, sensitization of gCl shifted membrane potential over a range of about 15 mV.
High‐frequency stimulation of the subthalamic nucleus modulates the activity of pedunculopontine neurons through direct activation of excitatory fibres as well as through indirect activation of inhibitory pallidal fibres in the rat
Authors: Florio Tiziana , Scarnati Eugenio , Confalone Giuseppina , Minchella Daniela , Galati Salvatore , Stanzione Paolo , Stefani Alessandro , Mazzone Paolo
Published: February 2007

Recent data suggest a potential role of pedunculopontine nucleus (PPN) electrical stimulation in improving gait and posture in Parkinson's disease. Because the PPN receives fibres from the subthalamic nucleus (STN), we investigated the effects of STN‐high‐frequency stimulation (HFS) on PPN neuronal activity in intact rats and in rats bearing either an ibotenate lesion of the entopeduncular nucleus (EP) or a lesion of the substantia nigra (SN). The main response of PPN neurons to STN single‐shock stimulations in the three experimental groups was a short latency (4.5 ± 2.1 ms) and brief (15.3 ± 6.5 ms) excitation. This response was maintained during 1–5 s of STN‐HFS (130 Hz, 60 µs, 100–1000 µA). In EP‐lesioned rats the percentage (75.0%) of PPN neurons showing a modulation of activity following STN‐HFS was significantly higher compared with that observed in intact (39.7%) and in SN‐lesioned rats (35.4%). Furthermore, in EP‐lesioned rats the most frequent response of PPN neurons following STN‐HFS was a 5–20 s excitation, which was present in 76.6% of responsive neurons in comparison to 15.4% and 9.1% of neurons responsive in intact and in 6‐hydroxydopamine‐lesioned rats, respectively. Neurons responsive to STN‐HFS in the three experimental groups showed either a sharp positively skewed distribution of interspike intervals or multisecond oscillations in autocorrelograms. The results support that STN‐HFS modulates the PPN through a balance of excitatory and inhibitory influences, which may be independent from the dopaminergic nigral neurons. In the absence of inhibitory EP fibres, the direct excitatory influence exerted by the STN on the PPN appears to predominate.
Characterization of a transneuronal cytokine family Cbln − regulation of secretion by heteromeric assembly
Authors: Iijima Takatoshi , Miura Eriko , Matsuda Keiko , Kamekawa Yuichi , Watanabe Masahiko , Yuzaki Michisuke
Published: February 2007

Cbln1, a member of the C1q and tumor necrosis factor superfamily, plays crucial roles as a cerebellar granule cell‐derived transneuronal regulator of synapse integrity and plasticity in Purkinje cells. Although other Cbln family members, Cbln2–Cbln4, have distinct spatial and temporal patterns of expression throughout the CNS, their biochemical and biological properties have remained largely uncharacterized. Here, we demonstrated that in mammalian heterologous cells, Cbln2 and Cbln4 were secreted as N‐linked glycoproteins, like Cbln1. In contrast, despite the presence of a functional signal sequence, Cbln3 was not secreted when expressed alone but was retained in the endoplasmic reticulum (ER) or cis‐Golgi because of its N‐terminal domain. All members of the Cbln family formed not only homomeric but also heteromeric complexes with each other in vitro. Accordingly, when Cbln1 and Cbln3 were co‐expressed in heterologous cells, a proportion of the Cbln1 proteins was retained in the ER or cis‐Golgi; conversely, some Cbln3 proteins were secreted together with Cbln1. Similarly, in wild‐type granule cells expressing Cbln1 and Cbln3, Cbln3 proteins were partially secreted and reached postsynaptic sites on Purkinje cell dendrites, while Cbln3 was almost completely degraded in cbln1‐null granule cells. These results indicate that like Cbln1, Cbln2 and Cbln4 may also serve as transneuronal regulators of synaptic functions in various brain regions. Furthermore, heteromer formation between Cbln1 and Cbln3 in cerebellar granule cells may modulate each other's trafficking and signaling pathways; similarly, heteromerization of other Cbln family proteins may also have biological significance in other neurons.
Differential cortical activity for precision and whole‐hand visually guided grasping in humans
Authors: Begliomini Chiara , Wall Matthew B. , Smith Andrew T. , Castiello Umberto
Published: February 2007

Effective grasping involves the remarkable ability to implement multiple grasp configurations such as precision grip (PG; opposition between the index finger and thumb) and whole‐hand grasp (WHG), depending on the properties of the object grasped (e.g. size, shape and weight). In the monkey brain, different groups of cells in the anterior–lateral bank of the intraparietal sulcus (area AIP) are differentially active for various hand configurations during grasping of differently shaped objects. Visually guided grasping studies in humans suggest the anterior intraparietal sulcus (aIPS) as the homologue of macaque area AIP, but leave unresolved the question of whether activity in human aIPS reflects the relationship between object size and grasp configuration, as in macaques. To address this issue, a human fMRI study was conducted in which objects were grasped with the right hand while object size was varied. The results indicated that the left aIPS was active when the subjects naturally adopted a PG to grasp the small object but showed a much weaker response when subjects naturally adopted a WHG to grasp the large object. The primary motor cortex and somatosensory cortices were active for both PG and WHG. Our results suggest that, in humans, the aIPS is centrally involved in determining the type of grasp.
Identification of self‐replicating multipotent progenitors in the embryonic nervous system by high Notch activity and Hes5 expression
Authors: Basak Onur , Taylor Verdon
Published: February 2007

Discrimination of neural stem cells from other progenitors in the developing mammalian brain has been hampered by the lack of specific markers. Identifying the progenitor pools and signalling pathways that guide mammalian neurogenesis are central to understanding the complex mechanisms that govern development of the nervous system. Notch signalling plays a pivotal role in the development of the mammalian nervous system by maintaining multipotent neural stem cells and regulating their fate. In order to identify putative neural stem cells in situ, we generated transgenic mice that express Green Fluorescent Protein (GFP) and report Notch signalling activity in the developing CNS. Here we show the subdivision of progenitors within the neural tube of these mice. We purify progenitors from the neural tube and show that cells with the highest levels of Notch‐reporter activity have self‐renewal capability and multipotency, whereas those lacking Hes5 expression do not form neurospheres in vitro. Using marker protein co‐expression and cell sorting, we show that both neuroepithelial cells as well as some radial glia at all axial levels of the embryonic neural tube display active Notch signalling. However, Tbr2‐positive basal progenitors of the developing telencephalon and differentiating Islet1/2‐ and Lim1‐positive motor neurons outside the ventricular zone do not express Hes5‐GFP. Quantitative analysis showed that Hes5 expression correlates better with neural stem cell potential than expression of the related gene Hes1. Thus, Notch activity through Hes5 identifies multipotent progenitors with stem cell properties and subdivides the different progenitors into defined pools.
Bilateral high‐frequency stimulation of the subthalamic nucleus on attentional performance: transient deleterious effects and enhanced motivation in both intact and parkinsonian rats
Authors: Baunez Christelle , Christakou Anastasia , Chudasama Yogita , Forni Claude , Robbins Trevor W.
Published: February 2007

It is now well established that subthalamic nucleus high‐frequency stimulation (STN HFS) alleviates motor problems in Parkinson's disease. However, its efficacy for cognitive function remains a matter of debate. The aim of this study was to assess the effects of STN HFS in rats performing a visual attentional task. Bilateral STN HFS was applied in intact and in bilaterally dopamine (DA)‐depleted rats. In all animals, STN HFS had a transient debilitating effect on all the variables measured in the task. In DA‐depleted rats, STN HFS did not alleviate the deficits induced by the DA lesion such as omissions and latency to make correct responses, but induced perseverative approaches to the food magazine, an indicator of enhanced motivation. In sham‐operated controls, STN HFS significantly reduced accuracy and induced perseverative behaviour, mimicking partially the effects of bilateral STN lesions in the same task. These results are in line with the hypothesis that STN HFS only partially mimics inactivation of STN produced by lesioning and confirm the motivational exacerbation induced by STN inactivation.
Regulated proteolytic processing of LRP6 results in release of its intracellular domain
Authors: Mi Kaihong , Johnson Gail V. W.
Published: February 2007

Low‐density lipoprotein receptor‐related protein 6 (LRP6) is a member of low‐density lipoprotein receptor (LDLR) family which cooperates with Frizzled receptors to transduce the canonical Wnt signal. As a critical component of the canonical Wnt pathway, LRP6 is essential for appropriate brain development, however, the mechanism by which LRP6 facilitates Wnt canonical signaling has not been fully elucidated. Interestingly, LRP6 which lacks its extracellular domain can constitutively activate TCF/LEF and potentiate the Wnt signal. Further, the free cytosolic tail of LRP6 interacts directly with glycogen synthase kinase (GSK3) and inhibits GSK3’s activity in the Wnt canonical pathway which results in increased TCF/LEF activation. However, whether these truncated forms of LRP6 are physiologically relevant is unclear. Recent studies have shown that other members of the LDLR family undergo γ‐secretase dependent regulated intramembrane proteolysis (RIP). Using independent experimental approaches, we show that LRP6 also undergoes RIP. The extracellular domain of LRP6 is shed and released into the surrounding milieu and the cytoplasmic tail is cleaved by γ‐secretase‐like activity to release the intracellular domain. Furthermore, protein kinase C, Wnt 3a and Dickkopf‐1 modulate this process. These findings suggest a novel mechanism for LRP6 in Wnt signaling: induction of ectodomain shedding of LRP6, followed by the γ‐secretase involved proteolytic releasing its intracellular domain (ICD) which then binds to GSK3 inhibiting its activity and thus activates the canonical Wnt signaling pathway.
Cerebrospinal fluid acetylcholinesterase changes after treatment with donepezil in patients with Alzheimer’s disease
Authors: García‐Ayllón María‐Salud , Silveyra María‐Ximena , Andreasen Niels , Brimijoin Stephen , Blennow Kaj , Sáez‐Valero Javier
Published: February 2007

We analyzed whether donepezil differently influences acetylcholinesterase (AChE) variants from cerebrospinal fluid (CSF) in patients with Alzheimer’s disease (AD) after long‐term treatment. Overall CSF‐AChE activity in AD patients before treatment was not different from controls, but the ratio between the major tetrameric form, G4, and the smaller G1 and G2 species was significantly lower. AChE levels at study outset were found to correlate positively with β‐amyloid 1–42 (Aβ42). When patients were re‐examined after 12 months treatment with donepezil, there was a remarkable increase in both the G4 and the lighter species of CSF AChE. As compared with placebo, donepezil caused decreases in the percentage of AChE that failed to bind to the lectin concanavalin A and the antibody AE1. These non‐binding species comprised primarily a small subset of G1 and G2 forms. In treated patients, these light variants were the only subset of CSF AChE that correlated with CSF‐Aβ42 levels. Sodium dodecyl sulfate–polyacrylamide gel electrophoresis analysis showed that a 77‐kDa band, attributed in part to inactive AChE, was lower in AD patients than in controls. Unlike enzyme activity, the intensity of this band did not increase after donepezil treatment. The varying responses of different AChE species to ChE‐I treatment suggest different modes of regulation, which may have therapeutic implications.
Suppression of reactive oxygen species production enhances neuronal survival in vitro and in vivo in the anoxia‐tolerant turtle Trachemys scripta
Authors: Milton Sarah L. , Nayak Gauri , Kesaraju Shailaja , Kara Laurie , Prentice Howard M.
Published: February 2007

Hypoxia‐ischemia with reperfusion is known to cause reactive oxygen species‐related damage in mammalian systems, yet, the anoxia tolerant freshwater turtle is able to survive repeated bouts of anoxia/reoxygenation without apparent damage. Although the physiology of anoxia tolerance has been much studied, the adaptations that permit survival of reoxygenation stress have been largely ignored. In this study, we examine ROS production in the turtle striatum and in primary neuronal cultures, and examine the effects of adenosine (AD) on cell survival and ROS. Hydroxyl radical formation was measured by the conversion of salicylate to 2,3‐dihydroxybenzoic acid (2,3‐DHBA) using microdialysis; reoxygenation after 1 or 4 h anoxia did not result in increased ROS production compared with basal normoxic levels, nor did H2O2 increase after anoxia/reoxygenation in neuronally enriched cell cultures. Blockade of AD receptors increased both ROS production and cell death in vitro, while AD agonists decreased cell death and ROS. As turtle neurons proved surprisingly susceptible to externally imposed ROS stress (H2O2), we propose that the suppression of ROS formation, coupled to high antioxidant levels, is necessary for reoxygenation survival. As an evolutionarily selected adaptation, the ability to suppress ROS formation could prove an interesting path to investigate new therapeutic targets in mammals.
The Impacts of the State Children's Health Insurance Program on Children Who Enroll: Findings from Ten States
Authors: Kenney Genevieve
Published: February 2007

Objective. Examine the extent to which enrollment in the State Children's Health Insurance Program (SCHIP) affects access to care and service use in 10 states that account for over 60 percent of all SCHIP enrollees.

Data Sources/Study Setting. Surveys of 16,700 SCHIP enrollees were conducted in 2002 as part of a congressionally mandated study. Three domains of SCHIP enrollees were included: (1) children who were recently enrolled in SCHIP, (2) those who had been enrolled in SCHIP for 5 months or more, and (3) those who had recently disenrolled from SCHIP. Response rates varied across states and domains but were clustered between 75 and 80 percent. Five different types of indicators were examined: (1) service use; (2) unmet need; (3) parental perceptions about being able to meet their child's health care needs; (4) presence and type of a usual source of care; and (5) provider communication and accessibility.

Study Design. The experiences SCHIP enrollees have while on the program are compared with those a separate sample of children had before enrolling using a separate sample pretest and posttest design, controlling for observable characteristics of the children and their families.

Data Collection/Extraction Methods. The sample was drawn based on a list frame of SCHIP enrollees. The survey was administered in English and Spanish, by Computer‐Assisted Telephone Interviewing (CATI). Field follow‐up was used to locate families who could not be reached by telephone and these interviews were conducted by cellular telephone.

Principal Findings. SCHIP enrollment was found to improve access to care along a number of different dimensions, other things equal, particularly relative to being uninsured. Established SCHIP enrollees were more likely to receive office visits, preventive health and dental care, and specialty care, more likely to have a usual source for medical and dental care and to report better provider communication and accessibility, and less likely to have unmet needs, financial burdens, and parental worry associated with meeting their child's health care needs. The findings are robust with respect to alternative specifications and hold up for individual states and subgroups.

Conclusions. Enrollment in SCHIP appears to be improving children's access to primary health care services, which in turn is causing parents to have greater peace of mind about meeting their children's needs.
Establishing the Essential Nursing Competencies for Genetics and Genomics
Authors: Jenkins Jean , Calzone Kathleen A.
Published: February 2007

Purpose: To describe the development and process of consensus used to establish essential genetic and genomic nursing competencies relevant to the entire nursing profession in the United States (US) regardless of academic preparation, role, practice setting, or clinical specialty.

Organizing Construct: Rogers' diffusion of innovation theory applied to the adoption of genetics and genomics as the central science for health care.

Methods: Multiphased national nursing initiative to develop, refine, and establish with consensus essential competencies in genetics and genomics for all nurses.

Findings: Genetics and genomics have emerged as the central science for health care in the 21st century, transforming recommendations for nursing education, practice, regulation and quality control.

Conclusion: The Essential Nursing Competencies and Curricula Guidelines for Genetics and Genomics indicate the minimal criteria for competency in genetics and genomics for the entire nursing profession in the US.