bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disruption of hippocampus‐regulated behavioural and cognitive processes by heterozygous constitutive deletion of SynGAP
Authors: Muhia Mary , Yee Benjamin K. , Feldon Joram , Markopoulos Foivos , Knuesel Irene 
Published: January 2010

AbstractThe brain‐specific Ras/Rap‐GTPase activating protein (SynGAP) is a prime candidate linking N‐methyl‐d‐aspartate receptors to the regulation of the ERK/MAP kinase signalling cascade, suggested to be essential for experience‐dependent synaptic plasticity. Here, we evaluated the behavioural phenotype of SynGAP heterozygous knockout mice (SG+/−), expressing roughly half the normal levels of SynGAP. In the cognitive domain, SG+/− mice demonstrated severe working and reference memory deficits in the radial arm maze task, a mild impairment early in the transfer test of the water maze task, and a deficiency in spontaneous alternation in an elevated T‐maze. In the non‐cognitive domain, SG+/− mice were hyperactive in the open field and appeared less anxious in the elevated plus maze test. In contrast, object recognition memory performance was not impaired in SG+/− mice. The reduction in SynGAP thus resulted in multiple behavioural traits suggestive of aberrant cognitive and non‐cognitive processes normally mediated by the hippocampus. Immunohistochemical evaluation further revealed a significant reduction in calbindin‐positive interneurons in the hippocampus and doublecortin‐positive neurons in the dentate gyrus of adult SG+/− mice. Heterozygous constitutive deletion of SynGAP is therefore associated with notable behavioural as well as morphological phenotypes indicative of hippocampal dysfunction. Any suggestion of a possible causal link between them however remains a matter for further investigation.
Visual restoration and transplant connectivity in degenerate rats implanted with retinal progenitor sheets
Authors: Seiler M. J. , Aramant R. B. , Thomas B. B. , Peng Q. , Sadda S. R. , Keirstead H. S. 
Published: January 2010

AbstractThe aim of this study was to determine whether retinal progenitor layer transplants form synaptic connections with the host and restore vision. Donor retinal sheets, isolated from embryonic day 19 rat fetuses expressing human placental alkaline phosphatase (hPAP), were transplanted to the subretinal space of 18 S334ter‐3 rats with fast retinal degeneration at the age of 0.8–1.3 months. Recipients were killed at the age of 1.6–11.8 months. Frozen sections were analysed by confocal immunohistochemistry for the donor cell label hPAP and synaptic markers. Vibratome slices were stained for hPAP, and processed for electron microscopy. Visual responses were recorded by electrophysiology from the superior colliculus (SC) in 12 rats at the age of 5.3–11.8 months. All recorded transplanted rats had restored or preserved visual responses in the SC corresponding to the transplant location in the retina, with thresholds between −2.8 and −3.4 log cd/m2. No such responses were found in age‐matched S334ter‐3 rats without transplants, or in those with sham surgery. Donor cells and processes were identified in the host by light and electron microscopy. Transplant processes penetrated the inner host retina in spite of occasional glial barriers between transplant and host. Labeled neuronal processes were found in the host inner plexiform layer, and formed apparent synapses with unlabeled cells, presumably of host origin. In conclusion, synaptic connections between graft and host cells, together with visual responses from corresponding locations in the brain, support the hypothesis that functional connections develop following transplantation of retinal layers into rodent models of retinal degeneration.
Stable individual differences in number discrimination in infancy
Authors: Libertus Melissa E. , Brannon Elizabeth M. 
Published: January 2010

AbstractPrevious studies have shown that as a group 6‐month‐old infants successfully discriminate numerical changes when the values differ by at least a 1:2 ratio but fail at a 2:3 ratio (e.g. 8 vs. 16 but not 8 vs. 12). However, no studies have yet examined individual differences in number discrimination in infancy. Using a novel numerical change detection paradigm, we present more direct evidence that infants’ numerical perception is ratio‐dependent even within the range of discriminable ratios and thus adheres to Weber’s Law. Furthermore, we show that infants’ numerical discrimination at 6 months reliably predicts their numerical discrimination abilities but not visual short‐term memory at 9 months. Thus, individual differences in numerical discrimination acuity may be stable within the first year of life and provide important avenues for future longitudinal research exploring the relationship between infant numerical discrimination and later developing math achievement.
Temporal dysregulation of cortical gene expression in the isolation reared Wistar rat
Authors: Murphy Keith J. , Ter Horst Judith P. F. , Cassidy Andrew W. , DeSouza Ian E. J. , Morgunova Marina , Li Christine , Connole Laura M. , O’Sullivan Niamh C. , Loscher Jennifer S. , Brady Angela T. , Rombach Nanette , Connellan Joanna , McGettigan Paul A. , Scully Darren , Fedriani Rocio , Lukasz Bartlomiej , Moran Mary P. , McCabe Olive M. , Wantuch Caitlin M. , Hughes Zoe A. , Mulvany Sean K. , Higgins Desmond G. , Pangalos Menelas N. , Marquis Karen L. , O’Connor William T. , Ring Robert H. , Von Schack David , Regan Ciaran M. 
Published: January 2010

J. Neurochem. (2010) 113, 601–614.AbstractThe critical sequence of molecular, neurotransmission and synaptic disruptions that underpin the emergence of psychiatric disorders like schizophrenia remain to be established with progress only likely using animal models that capture key features of such disorders. We have related the emergence of behavioural, neurochemical and synapse ultrastructure deficits to transcriptional dysregulation in the medial prefrontal cortex of Wistar rats reared in isolation. Isolation reared animals developed sensorimotor deficits at postnatal day 60 which persisted into adulthood. Analysis of gene expression prior to the emergence of the sensorimotor deficits revealed a significant disruption in transcriptional control, notably of immediate early and interferon‐associated genes. At postnatal day 60 many gene transcripts relating particularly to GABA transmission and synapse structure, for example Gabra4, Nsf, Syn2 and Dlgh1, transiently increased expression. A subsequent decrease in genes such as Gria2 and Dlgh2 at postnatal day 80 suggested deficits in glutamatergic transmission and synapse integrity, respectively. Microdialysis studies revealed decreased extracellular glutamate suggesting a state of hypofrontality while ultrastructural analysis showed total and perforated synapse complement in layer III to be significantly reduced in the prefrontal cortex of postnatal day 80 isolated animals. These studies provide a molecular framework to understand the developmental emergence of the structural and behavioural characteristics that may in part define psychiatric illness.
Angiotensin‐II type 1 receptor (AT1R) and alpha‐1D adrenoceptor form a heterodimer during pregnancy‐induced hypertension
Authors: Lourdes González‐Hernández M. de , Godínez‐Hernández D. , Bobadilla‐Lugo R. A. , López‐Sánchez P. 
Published: January 2010

Summary1 Pregnancy courses with low response to angiotensin II and adrenergic agonists. In preeclampsia, both effects are reverted. It is known that angiotensin II regulates adrenergic system. It is not known, however, the interaction between both systems receptors.2 Our aim was to study if AT1R and α1D adrenoceptor heterodimerize in preeclampsia.3 We used subrenal aorctic coarctation in pregnant rats. Aortic tissues were prepared for confocal imaging and coimmunoprecipitated for α1D and AT1receptors.4 We found that AT1R and α1D adrenoceptor heterodimerize in both, healthy and preeclamptic groups. In healthy pregnant rats, heterodimer is barely detected. In preeclamptic rats however, we found higher heterodimerization.5 These results suggest that AT1R and α1D ‐adrenoceptor may form heterodimers, and may play a role in preeclampsia.
Evidence Complexity and Information Search in the Decision to Restate Prior‐Period Financial Statements
Authors: RICCHIUTE DAVID N. 
Published: January 2010

ABSTRACTFramed in the decision to restate financial statements, this study addresses whether behavior predicted by competing theories depends on the complexity of evidence. Two experiments observe the information‐search behavior of auditors responsible for investigating their firm's prior opinion. Experiment 1 shows that auditors confronted with few (many) summarized statements that replicate in form the materials used in prior research prefer to first search statements that are inconsistent (consistent) with the prior‐period accounting. This result generally corroborates research in accounting and confirms the predictions of information‐quantity theory in psychology. In contrast, experiment 1 also shows that, when materials mimic the detailed documents common in practice, the results are different: Auditors confronted either with few or with many detailed documents prefer to search inconsistent documents first. This result confirms the predictions of evidence‐complexity theory in psychology and shows that, compared to the materials on which prior research relies, detailed documents, such as memos, emails, letters, and analyses, drive information search toward inconsistent evidence. Experiment 2 probes further and finds that auditors evaluate documents bearing notes inscribed after the documents were prepared to be more inconsistent with the prior‐period accounting, and that the dispersion in search behavior may be reliably conditional on the presence of notes.
Novel ruthenium complexes as potential drugs for Chagas's disease: enzyme inhibition and in vitro/in vivo trypanocidal activity
Authors: Silva Jean Jerley Nogueira , Guedes Paulo Marcos Matta , Zottis Aderson , Balliano Tatiane Luciano , Nascimento Silva Francisco Ordelei , França Lopes Luiz Gonzaga , Ellena Javier , Oliva Glaucius , Andricopulo Adriano Defini , Franco Douglas Wagner , Silva João Santana 
Published: January 2010

Background and purpose:  The discovery of the pharmacological functions of nitric oxide has led to the development of NO donor compounds as therapeutic agents. A new generation of ruthenium NO donors, cis‐[Ru(NO)(bpy)2L]Xn, has been developed, and our aim was to show that these complexes are able to lyse Trypanosoma cruzi in vitro and in vivo.Experimental approach:  NO donors were incubated with T. cruzi and their anti‐T. cruzi activities evaluated as the percentage of lysed parasites compared to the negative control. In vivo, trypanocidal activity was evaluated by observing the levels of parasitaemia, survival rate and elimination of amastigotes in mouse myocardial tissue. The inhibition of GAPDH was monitored by the biochemical reduction of NAD+ to NADH.Key results:  The NO donors cis‐[Ru(NO)(bpy)2L]Xn presented inhibitory effects on T. cruzi GAPDH (IC50 ranging from 89 to 153 µM). The crystal structure of the enzyme shows that the inhibitory mechanism is compatible with S‐nitrosylation of the active cysteine (cys166) site. Compounds cis‐[Ru(NO)(bpy)2imN](PF6)3 and cis‐[Ru(NO)(bpy)2SO3]PF6, at a dose of 385 nmol·kg−1, yielded survival rates of 80 and 60%, respectively, in infected mice, and eradicated any amastigotes from their myocardial tissue.Conclusions and implications:  The ruthenium compounds exhibited potent in vitro and in vivo trypanocidal activities at doses up to 1000‐fold lower than the clinical dose for benznidazole. Furthermore, one mechanism of action of these compounds is via the S‐nitrosylation of Cys166 of T. cruzi GAPDH. Thus, these compounds show huge potential as candidates for the development of new drugs for the treatment of Chagas's disease.This article is commented on by Machado et al., pp. 258–259 of this issue. To view this commentary visit http://dx.doi.org/10.1111/j.1476‐5381.2010.00662.x and to view a related paper in this issue by Guedes et al. visit http://dx.doi.org/10.1111/j.1476‐5381.2010.00576.x
A cannabinoid receptor, sensitive to O‐1918, is involved in the delayed hypotension induced by anandamide in anaesthetized rats
Authors: Zakrzeska Agnieszka , Schlicker Eberhard , Baranowska Marta , Kozłowska Hanna , Kwolek Grzegorz , Malinowska Barbara 
Published: January 2010

Background and purpose: Intravenous injection of the endocannabinoid anandamide induces complex cardiovascular changes via cannabinoid CB1, CB2and vanilloid TRPV1 receptors. Recently, evidence has been accumulating thatin vitro, but notin vivo, anandamide relaxes blood vessels, via an as yet unidentified, non‐CB1vascular cannabinoid receptor, sensitive to O‐1918 (1,3‐dimethoxy‐5‐2‐[(1R,6R)‐3‐methyl‐6‐(1‐methylethenyl)‐2‐cyclohexen‐1‐yl]‐benzene). We here examined whether the anandamide‐induced hypotension in urethane‐anaesthetized rats was also mediated via a non‐CB1vascular cannabinoid receptor.Experimental approach: Effects of two antagonists (O‐1918 and cannabidiol) of the non‐CB1vascular cannabinoid receptor on anandamide‐induced changes in mean, systolic and diastolic blood pressure (MBP, SBP, DBP), mesenteric (MBF) and renal (RBF) blood flow and heart rate (HR) in urethane‐anaesthetized rats was examined.Key results: In anaesthetized rats, anandamide (1.5–3 µmol·kg−1) and its stable analogue methanandamide (0.5 µmol·kg−1) caused a delayed and prolonged decrease in MBP, SBP, DBP, MBF and RBF by about 10–30% of the respective basal values without changing HR. In pithed rats, anandamide (3 µmol·kg−1) decreased blood pressure by about 15–20% of the basal value without affecting HR, MBF and RBF. All vascular changes were reduced by about 30–70% by cannabidiol and O‐1918 (3 µmol·kg−1, each).Conclusions and implications: Non‐CB1cannabinoid vascular receptors, sensitive to O‐1918, contribute to the hypotensive effect of anandamide in anaesthetized rats. Activation of these receptors may be therapeutically important as the endocannabinoid system could be activated as a compensatory mechanism in various forms of hypertension.
TheGinkgo bilobaextract EGb 761®and its main constituent flavonoids and ginkgolides increase extracellular dopamine levels in the rat prefrontal cortex
Authors: Yoshitake T , Yoshitake S , Kehr J 
Published: January 2010

Background and purpose: Experimental and clinical data suggest that extracts ofGinkgo bilobaimprove cognitive function. However, the neurochemical correlates of these effects are not yet fully clarified. The purpose of this study was to examine the effects of acute and repeated oral administration of the standardized extract EGb 761®on extracellular levels of dopamine, noradrenaline and serotonin (5‐HT), and the dopamine metabolites 3,4‐dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the prefrontal cortex (PFC) and striatum of conscious rats.Experimental approach: Monoamines and their metabolites were monitored by the use of microdialysis sampling and HPLC with electrochemical or fluorescence detection.Key results: A single oral dose of EGb 761 (100 mg·kg−1) had no effect on monoamine levels. However, following chronic (100 mg·kg−1/14 days/once daily) treatment, the same dose significantly increased extracellular dopamine and noradrenaline levels, while 5‐HT levels were unaffected. Chronic treatment with EGb 761 showed dose‐dependent increases in frontocortical dopamine levels and, to a lesser extent, in the striatum. The extracellular levels of HVA and DOPAC were not affected by either acute or repeated doses. Treatment with the main constituents of EGb 761 revealed that the increase in dopamine levels was mostly caused by the flavonol glycosides and ginkgolide fractions, whereas bilobalide treatment was without effect.Conclusions and implications: The present results demonstrate that chronic but not acute treatment with EGb 761 increased dopaminergic transmission in the PFC. This finding may be one of the mechanisms underlying the reported effects ofG. bilobain improving cognitive function.
Deoxyelephantopin, a novel multifunctional agent, suppresses mammary tumour growth and lung metastasis and doubles survival time in mice
Authors: Huang Chi‐Chang , Lo Chiu‐Ping , Chiu Chih‐Yang , Shyur Lie‐Fen 
Published: January 2010

Background and purpose:  Elephantopus scaber L. (Asteraceae) is a traditional herbal medicine with anti‐cancer effects. We evaluated the in vitro and in vivo efficacy of a major sesquiterpene lactone constituent of E. scaber, deoxyelephantopin (DET), against mammary adenocarcinoma and the underlying molecular mechanism.Experimental approach:  A variety of cellular assays, immunoblotting and immunohistochemistry, as well as both orthotopic and metastatic TS/A tumour models in BALB/c mice, were used. Test mice were pretreated and post‐treated with DET or paclitaxel and mammary tumour growth evaluated.Key results:  DET (≤2 µg·mL−1) significantly inhibited colony formation, cell proliferation, migration and invasion of TS/A cells and induced G2/M arrest and apoptosis in TS/A cells. c‐Jun N‐terminal kinase‐mediated p21Waf1/Cip1 expression and caspase activation cascades were up‐regulated by DET, effects suppressed by N‐acetyl‐L‐cysteine. Moreover, tumour necrosis factor α‐induced matrix metalloproteinase‐9 enzyme activity and expression and nuclear factor‐kappa B activation were abolished by DET. Pretreatment with DET was more effective than paclitaxel, for profound suppression of orthotopic tumour growth (99% vs. 68% reduction in tumour size) and lung metastasis of TS/A cells (82% vs. 63% reduction in metastatic pulmonary foci) and prolonged median survival time (56 vs. 37 days, P < 0.01) in mice. The levels of cyclooxygenase‐2 and vascular endothelial growth factor in metastatic lung tissues of TS/A‐bearing mice were attenuated by DET.Conclusions and implications:  Our data provide evidence for the suppression of mammary adenocarcinoma by DET with several mechanisms and suggest that DET has potential as a chemopreventive agent for breast cancer.
Bidirectional modulation of isoflurane potency by intrathecal tetrodotoxin and veratridine in rats
Authors: Zhang Y , Guzinski M , Eger II EI , Laster MJ , Sharma M , Harris RA , Hemmings Jr HC 
Published: January 2010

Background and purpose:  Results from several studies point to voltage‐gated Na+ channels as potential mediators of the immobility produced by inhaled anaesthetics. We hypothesized that the intrathecal administration of tetrodotoxin, a drug that blocks Na+ channels, should enhance anaesthetic potency, and that concurrent administration of veratridine, a drug that augments Na+ channel opening, should reverse the increase in potency.Experimental approach:  We measured the change in isoflurane potency for reducing movement in response to a painful stimulus as defined by MAC (minimum alveolar concentration of anaesthetic required to abolish movement in 50% of subjects) caused by intrathecal infusion of various concentrations of tetrodotoxin into the lumbothoracic subarachnoid space of rats, and the change in MAC caused by the administration of a fixed dose of tetrodotoxin plus various doses of intrathecal veratridine.Key results:  Intrathecal infusion of tetrodotoxin (0.078–0.63 µM) produced a reversible dose‐related decrease in MAC, of more than 50% at the highest concentration. Intrathecal co‐administration of veratridine (1.6–6.4 µM) reversed this decrease in a dose‐related manner, with nearly complete reversal at the highest veratridine dose tested.Conclusions and implications:  Intrathecal administration of tetrodotoxin increases isoflurane potency (decreases isoflurane MAC), and intrathecal administration of veratridine counteracts this effect in vivo. These findings are consistent with a role for voltage‐gated Na+ channel blockade in the immobility produced by inhaled anaesthetics.
Origin of stratified basal ice in outlet glaciers of Vatnajökull and Öræfajökull, Iceland
Authors: LARSON GRAHAME J. , LAWSON DANIEL E. , EVENSON EDWARD B. , KNUDSEN ÓSKAR , ALLEY RICHARD B. , PHANIKUMAR MANTHA S. 
Published: January 2010

Larson, G.J., Lawson, D.E., Evenson, E.B., Knudsen, Ó., Alley, R.B. & Phanikumar, M.S. 2010: Origin of stratified basal ice in outlet glaciers of Vatnajökull and Öræfajökull, Iceland. Boreas, Vol. 39, pp. 457–470. 10.1111/j.1502‐3885.2009.00134.x. ISSN 0300‐9483.During the period 2000–2005, we collected samples of englacial ice, vent water, frazil/anchor ice and stratified basal ice from warm‐based outlet glaciers of Vatnajökull and Öræfajökull, Iceland, and analysed them for 3H, 18O and D. Results of 3H analyses show that the stratified basal ice contains 3H from atmospheric thermonuclear testing and is younger than the englacial ice. Results of the 18O and D analyses show that frazil/anchor and stratified basal ice are both enriched by an average of 2.4‰ in 18O and 11‰ in D relative to vent water. These values are consistent with fractionation during partial freezing of supercooled subglacial water in an open system, one in which the remaining water is continuously removed and replenished by water of similar composition. The isotopic data and field observations do not support either a regelation or a thermal ad‐freeze‐on origin for the stratified basal ice.
How Levels of Interactivity in Tutorials Affect Students’ Learning of Modeling Transportation Problems in a Spreadsheet
Authors: Seal Kala Chand , Przasnyski Zbigniew H. , Leon Linda A. 
Published: January 2010

ABSTRACTDo students learn to model OR/MS problems better by using computer‐based interactive tutorials and, if so, does increased interactivity in the tutorials lead to better learning? In order to determine the effect of different levels of interactivity on student learning, we used screen capture technology to design interactive support materials for modeling and solving the transportation problem in a spreadsheet. A controlled experiment was carried out and the results indicate a general support for the effectiveness of interactive tutorials in enhancing students’ learning of modeling concepts. However, the study also found that excessive interactivity increased the cognitive load for the students and hindered their learning by making it difficult for them to consolidate concepts, integrate previous knowledge, and create meaningful mental models of the process.
Absenteeism in Undergraduate Business Education: A Proposed Model and Exploratory Investigation*
Authors: Burke Lisa A. 
Published: January 2010

ABSTRACTOne issue in undergraduate business education remaining underexamined is student absenteeism. In this article, the literature on undergraduate absenteeism is reviewed culminating in a proposed conceptual framework to guide future research, and an exploratory investigation of management students’ attitudes about absenteeism is conducted. Implications for research practice are discussed.
Obama in Asia: West Looks East After the “End of History”
Authors: MAHBUBANI KISHORE 
Published: January 2010

Twenty years after the fall of the Berlin Wall and the triumphant celebrations of the West, a new chapter of history has opened featuring the rising powers of Asia, led by China. Though embracing free markets, China has looked to its Confucian traditions instead of liberal democracy as the best route to good governance.Will China manage to achieve high growth and a harmonious society through a strong state and long‐range planning that puts messy Western democracy and its short‐term mindset to shame? Or, in the end, will the weak rule of law and absence of political accountability in a one‐party state undermine its promise?Francis Fukuyama and Kishore Mahbubani, the Singaporean thinker who has become the apostle of non‐Western modernity, debate these issues.In this section we also republish a collective memoir by George H.W. Bush, Mikhail Gorbachev, Margaret Thatcher and François Mitterrand, recalling their fears and hopes two decades ago as they brought the Cold War to an end.