bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neutralization of interleukin‐1β modifies the inflammatory response and improves histological and cognitive outcome following traumatic brain injury in mice
Authors: Clausen Fredrik , Hånell Anders , Björk Maria , Hillered Lars , Mir Anis K. , Gram Hermann , Marklund Niklas 
Published: July 2009

AbstractInterleukin‐1β (IL‐1β) may play a central role in the inflammatory response following traumatic brain injury (TBI). We subjected 91 mice to controlled cortical impact (CCI) brain injury or sham injury. Beginning 5 min post‐injury, the IL‐1β neutralizing antibody IgG2a/k (1.5 μg/mL) or control antibody was infused at a rate of 0.25 μL/h into the contralateral ventricle for up to 14 days using osmotic minipumps. Neutrophil and T‐cell infiltration and microglial activation was evaluated at days 1–7 post‐injury. Cognition was assessed using Morris water maze, and motor function using rotarod and cylinder tests. Lesion volume and hemispheric tissue loss were evaluated at 18 days post‐injury. Using this treatment strategy, cortical and hippocampal tissue levels of IgG2a/k reached 50 ng/mL, sufficient to effectively inhibit IL‐1βin vitro. IL‐1β neutralization attenuated the CCI‐induced cortical and hippocampal microglial activation (P < 0.05 at post‐injury days 3 and 7), and cortical infiltration of neutrophils (P < 0.05 at post‐injury day 7). There was only a minimal cortical infiltration of activated T‐cells, attenuated by IL‐1β neutralization (P < 0.05 at post‐injury day 7). CCI induced a significant deficit in neurological motor and cognitive function, and caused a loss of hemispheric tissue (P < 0.05). In brain‐injured animals, IL‐1β neutralizing treatment resulted in reduced lesion volume, hemispheric tissue loss and attenuated cognitive deficits (P < 0.05) without influencing neurological motor function. Our results indicate that IL‐1β is a central component in the post‐injury inflammatory response that, in view of the observed positive neuroprotective and cognitive effects, may be a suitable pharmacological target for the treatment of TBI.
Choice strategies in Drosophila are based on competition between olfactory memories
Authors: Yin Yan , Chen Nannan , Zhang Shixing , Guo Aike 
Published: July 2009

AbstractThe brain mechanisms by which animals deal with multiple experiences to predict outcomes are not yet fully understood. We explored the choice strategies that flies use to assess degrees of disadvantage, as well as how flies weigh past and recent experiences to guide decisions. Drosophila were exposed to two conditioning events in a T‐maze: an odor paired with an electric shock followed by a second odor paired with an electric shock of a different intensity. Subsequently, flies were forced to choose between the two odors. We found that flies chose to avoid the more ‘dangerous’ odor by a linear subtraction mechanism that was based on two coexisting memories. We also found that flies weighed experiences of the same danger level (60 V electric shocks) according to the times when the experiences had occurred. More recent experiences had a greater impact and past experiences gradually became ‘overlooked’ during decisions as the time delay between the two events lengthened. However, the past memory was not so much disrupted as it was overshadowed by recent memories during decisions. Finally, when a past experience was more disadvantageous, wild‐type flies were able to coordinate both the temporal factor and the degree of disadvantage into their decisions. By contrast, amnesiac mutant flies made choices completely according to the temporal factor, ignoring the degree of disadvantage. Taken together, wild‐type flies are able to store multiple olfactory memories and can coherently evaluate learned experiences to guide their decisions according to the degree of disadvantage and/or the temporal factor.
l‐Glutamine‐induced apoptosis in microglia is mediated by mitochondrial dysfunction
Authors: Svoboda Nina , Kerschbaum Hubert H. 
Published: July 2009

AbstractUnder physiological conditions, astrocytes take up l‐glutamate from the synaptic gap, metabolize it to l‐glutamine and return it to neurons, where l‐glutamine is metabolized to l‐glutamate and stored in neurotransmitter vesicles. However, under pathological conditions, such as hepatic failure, l‐glutamine and ammonium are elevated globally in the brain. The Trojan horse hypothesis of l‐glutamine toxicity assumes that intramitochondrial hydrolysis of l‐glutamine enhances ammonium locally and leads to mitochondrial dysfunction. In the present study, we show that exposure of murine primary microglia as well as of the microglial cell‐line BV‐2 to l‐glutamine promotes chromatin condensation and formation of crescent‐like structures in the nucleus. Furthermore, l‐glutamine induced an increase in annexin‐V labelling, cell shrinkage (apoptotic volume decrease), cell fragmentation and formation of apoptotic bodies. Inhibition of the phosphate‐activated glutaminase with 6‐diazo‐5‐oxo‐l‐norleucine suppressed chromatin condensation and annexin‐V labelling in l‐glutamine‐exposed cells. In addition, inhibition of the glutamine synthetase with l‐methionine sulfoximine suppressed chromatin condensation and annexin‐V labelling in ammonium‐exposed cells. l‐Glutamine and ammonium enhanced production of reactive oxygen species, as detected with CM‐H2DCFDA. Apoptosis, induced by l‐glutamine, was inhibited either by the radical scavenger α‐tocopherol or by the nitric oxide synthase blocker N G‐methyl‐l‐arginine. Cyclosporin A, a ligand of the permeability transition pore complex component cyclophilin D, prevented l‐glutamine‐triggered apoptosis. Furthermore, blockade of caspase‐9 activity with Z‐LEHD‐FMK prevented l‐glutamine‐triggered apoptosis. Taken together, our results indicate that hydrolysis of l‐glutamine and, accordingly, accumulation of ammonium in mitochondria induce the intrinsic pathway of apoptosis, characterized by mitochondrial dysfunction and activation of caspase‐9, which activates caspase‐3.
Overexpression of 5‐HT2C receptors in forebrain leads to elevated anxiety and hypoactivity
Authors: Kimura Atsuko , Stevenson Paula L. , Carter Roderick N. , MacColl Gavin , French Karen L. , Paul Simons J. , Al‐Shawi Raya , Kelly Valerie , Chapman Karen E. , Holmes Megan C. 
Published: July 2009

AbstractThe 5‐HT2C receptor has been implicated in mood and eating disorders. In general, it is accepted that 5‐HT2C receptor agonists increase anxiety behaviours and induce hypophagia. However, pharmacological analysis of the roles of these receptors is hampered by the lack of selective ligands and the complex regulation of receptor isoforms and expression levels. Therefore, the exact role of 5‐HT2C receptors in mood disorders remain controversial, some suggesting agonists and others suggesting antagonists may be efficacious antidepressants, while there is general agreement that antagonists are beneficial anxiolytics. In order to test the hypothesis that increased 5‐HT2C receptor expression, and thus increased 5‐HT2C receptor signalling, is causative in mood disorders, we have undertaken a transgenic approach, directly altering the 5‐HT2C receptor number in the forebrain and evaluating the consequences on behaviour. Transgenic mice overexpressing 5‐HT2C receptors under the control of the CaMKIIα promoter (C2CR mice) have elevated 5‐HT2C receptor mRNA levels in cerebral cortex and limbic areas (including the hippocampus and amygdala), but normal levels in the hypothalamus, resulting in > 100% increase in the number of 5‐HT2C ligand binding sites in the forebrain. The C2CR mice show increased anxiety‐like behaviour in the elevated plus‐maze, decreased wheel‐running behaviour and reduced activity in a novel environment. These behaviours were observed in the C2CR mice without stimulation by exogenous ligands. Our findings support a role for 5‐HT2C receptor signalling in anxiety disorders. The C2CR mouse model offers a novel and effective approach for studying disorders associated with 5‐HT2C receptors.
Bar pressing for food: differential consequences of lesions to the anterior versus posterior pedunculopontine
Authors: Wilson David I. G. , MacLaren Duncan A. A. , Winn Philip 
Published: July 2009

AbstractThe pedunculopontine tegmental nucleus (PPTg) is in a key position to participate in operant reinforcement via its connections with the corticostriatal architecture and the medial reticular formation. Indeed, previous work has demonstrated that rats bearing lesions of the whole PPTg are impaired when learning to make two bar presses for amphetamine reinforcement. Anterior and posterior portions of the PPTg make different anatomical connections, including preferential projections by the anterior PPTg to substantia nigra pars compacta dopamine neurons and by the posterior PPTg to ventral tegmental area dopamine neurons. We wanted to assess the effects of anterior and posterior PPTg ibotenate lesions on rats learning simple and more complex schedules of natural reinforcement. We trained rats with lesions to the anterior PPTg (n = 11) and the posterior PPTg (n = 5) [and appropriate controls (n = 15)] to bar press for food on a variety of fixed‐ratio and variable‐ratio reinforcement schedules and then during extinction. We found that posterior PPTg‐lesioned rats bar pressed at lower rates, were slower to learn to bar press, and often had deficits characteristic of impaired learning and/or motivation. In contrast, anterior PPTg‐lesioned rats learned to bar press for reinforcement at normal rates. However, they made errors of perseveration and anticipation throughout many schedules, and pressed at a higher rate than controls during extinction, deficits best characterized as reflecting disorganized response control. Together, these data suggest that the anterior PPTg and posterior PPTg (and their related circuits) contribute differently to reinforcement learning, incentive motivation, and response control, processes that are considered to malfunction in drug addiction.
Antidepressant treatment facilitates dopamine release and drug seeking behavior in a genetic animal model of depression
Authors: Roth‐Deri Ilana , Friedman Alexander , Abraham Lital , Lax Elad , Flaumenhaft Yakov , Dikshtein Yahav , Yadid Gal 
Published: July 2009

AbstractAnhedonia and lack of motivation are core symptoms of depression. In contrast, hyper‐motivation and euphoria characterize intoxicated states. In order to explore the relationship between these two behavioral states we examined cocaine self‐administration tasks in an animal model of depression [Flinders Sensitive Line (FSL) rats]. We found that FSL rats exhibit sub‐sensitivity in their cocaine‐seeking behavior, which was normalized following a chronic treatment with the antidepressant desipramine. However, when the cocaine dosage was increased, FSL rats demonstrated a similar cocaine‐seeking behavior to that of controls. In light of dopamine’s central role in modulating cocaine reinforcement, we examined dopaminergic neurotransmission in the nucleus accumbens, a brain region implicated in the rewarding and hedonic effects of substances of misuse. FSL rats exhibited low but dose‐dependent increases in extracellular levels of dopamine in the nucleus accumbens after acute intravenous cocaine injection. Furthermore, by using the dopamine transporter blocker GBR‐12909 we were able to demonstrate that the low extracellular dopamine levels, observed in FSL rats, were a consequence of low dopamine release in the nucleus accumbens, as opposed to the possibility of increased uptake. Treatment of FSL rats with the antidepressant desipramine raised cocaine‐ and GBR‐12909‐induced dopamine release to the level of controls. This treatment also resulted in increased cocaine‐seeking behavior.
Rescue of abnormal phenotypes in δ2 glutamate receptor‐deficient mice by the extracellular N‐terminal and intracellular C‐terminal domains of the δ2 glutamate receptor
Authors: Torashima Takashi , Iizuka Akira , Horiuchi Hajime , Mitsumura Kazuhiro , Yamasaki Miwako , Koyama Chiho , Takayama Kiyohiko , Iino Masae , Watanabe Masahiko , Hirai Hirozaku 
Published: July 2009

AbstractThe δ2 glutamate receptor (GluRδ2) is expressed predominantly in cerebellar Purkinje cells. GluRδ2 knock‐out mice show impaired synaptogenesis and loss of long‐term depression (LTD) at parallel fiber/Purkinje cell synapses, and persistent multiple climbing fiber (CF) innervation of Purkinje cells, resulting in severe ataxia. To identify domains critical for GluRδ2 function, we produced various GluRδ2 deletion constructs. Using lentiviral vectors, those constructs were expressed in Purkinje cells of GluRδ2‐deficient mice at postnatal day (P) 6 or 7, and rescue of abnormal phenotypes was examined beyond P30. Most constructs failed to rescue the defects of GluRδ2‐deficient mice, mainly because they were not efficiently transferred to the postsynaptic sites. However, a construct carrying only the extracellular N‐terminal domain (NTD) and the intracellular C‐terminal domain (CTD) linked with the fourth transmembrane domain of GluRδ2 (NTD‐TM4‐CTD) caused incomplete, but significant rescue of ataxia, consistent with relatively better transport of the construct to the synapses. Notably, the expression of NTD‐TM4‐CTD in GluRδ2‐deficient Purkinje cells restored abrogated LTD, and aberrant CF territory in the molecular layer. Although the expression of NTD‐TM4‐CTD failed to rescue persistent multiple CF innervation of GluRδ2‐deficient Purkinje cells, a similar construct in which only TM4 was replaced with a transmembrane domain of CD4 successfully rescued the multiple CF innervation, probably due to more efficient transport of the protein to postsynaptic sites. These results suggest that NTD and CTD are critical domains of GluRδ2, which functions substantially without conventional ligand binding and ion channel structures.
Convergent structural responses of tropical forests to diverse disturbance regimes
Authors: Kellner James R. , Asner Gregory P. 
Published: July 2009

AbstractSize frequency distributions of canopy gaps are a hallmark of forest dynamics. But it remains unknown whether legacies of forest disturbance are influencing vertical size structure of landscapes, or space‐filling in the canopy volume. We used data from LiDAR remote sensing to quantify distributions of canopy height and sizes of 434 501 canopy gaps in five tropical rain forest landscapes in Costa Rica and Hawaii. The sites represented a wide range of variation in structure and natural disturbance history, from canopy gap dynamics in lowland Costa Rica and Hawaii, to stages and types of stand‐level dieback on upland Mauna Kea and Kohala volcanoes. Large differences in vertical canopy structure characterized these five tropical rain forest landscapes, some of which were related to known disturbance events. Although there were quantitative differences in the values of scaling exponents within and among sites, size frequency distributions of canopy gaps followed power laws at all sites and in all canopy height classes. Scaling relationships in gap size at different heights in the canopy were qualitatively similar at all sites, revealing a remarkable similarity despite clearly defined differences in species composition and modes of prevailing disturbance. These findings indicate that power‐law gap‐size frequency distributions are ubiquitous features of these five tropical rain forest landscapes, and suggest that mechanisms of forest disturbance may be secondary to other processes in determining vertical and horizontal size structure in canopies.
Haemorrhoids – a collagen disease?
Authors: Willis S. , Junge K. , Ebrahimi R. , Prescher A. , Schumpelick V. 
Published: July 2009

AbstractObjective  The cause of haemorrhoidal disease is unknown, epidemiological data and histopathological findings support the hypothesis that reduced connective tissue stability is associated with the incidence of haemorrhoids. Therefore the aim of this study was to analyse the quantity and quality of collagen formation in the corpus cavernosum recti in patients with III°/IV° haemorrhoids in comparison with persons without haemorrhoids.Method  Haemorrhoidectomy specimens of 31 patients with III°/IV° haemorrhoids were examined. The specimens of 20 persons who died a natural death and who had no haemorrhoidal disease served as the controls. The amount of collagen was estimated photometrically by calculating the collagen/protein ratio. The collagen I/III ratio served as parameter for the quality of collagen formation and was calculated using cross polarization spectroscopy.Results  Patients with haemorrhoids had a significantly reduced collagen/protein ratio (42.2 ± 16.2 μg/mg vs 72.5 ± 31.0 μg/mg; P = 0.02) and a significantly reduced collagen I/III ratio (2.0 ± 0.1 vs 4.6 ± 0.3; P < 0.001) compared with persons without haemorrhoidal disease. There was no correlation with patients’ age or gender.Conclusions  There is a fundamental disorder of collagen metabolism in patients with haemorrhoidal disease. It remains unclear whether this is due to exogenous or endogenous influences.
Improved survival after rectal cancer in Denmark
Authors: Bülow S. , Harling H. , Iversen L. H. , Ladelund S. ,   on behalf of The Danish Colorectal Cancer Group
Published: July 2009

AbstractObjective  In 1995, an analysis showed an inferior prognosis after rectal cancer in Denmark compared with the other Scandinavian countries. The Danish Colorectal Cancer Group (DCCG) was established with the aim of improving the prognosis, and in this study we present a survival analysis of patients treated from 1994 to 2006.Method  The study was based on the National Rectal Cancer Registry and the National Colorectal Cancer Database, supplemented with data from the Central Population Registry. The analysis included actuarial overall and relative survival.Results  A total of 10 632 patients were operated on. The overall 5‐year survival increased from 0.37 in 1994 to 0.51% in 2006; the improvement was greater in men (20% points) than in women (10% points), and greatest in stage III (20% points). The relative 5‐year survival increased from 0.46 to 0.62, including an improvement of 23% points in men and 9% points in women and the greatest in stage III (22% points).Conclusions  The prognosis has improved substantially, probably mainly because of initiatives taken by the DCCG, among which implementation of total mesorectal excision, improved staging and centralized treatment are considered most important.
Firm Profitability, State Ownership, and Top Management Turnover at the Listed Firms in China: A Behavioral Perspective
Authors: Shen Wei , Lin Chen 
Published: July 2009

ABSTRACTManuscript Type: EmpiricalResearch Question/Issue: We attempt to clarify the relationships between firm profitability, state ownership, and top management turnover at partially privatized firms by applying the behavioral theory of organizational search, which proposes that firms focus on target in performance evaluation.Research Findings/Results: Using data from a large sample of the listed firms in China from 1999 to 2002, we find that firm profitability and state ownership are negatively related to top management turnover only when firm profitability is below target (measured by industry median). We also find that top management turnover has a positive impact on subsequent firm profitability when it occurs under performance below target, but has a negative impact when it occurs under performance above target. Lastly, we find that top management turnover under performance below target has a positive impact on subsequent firm profitability when the state is not the largest shareholder, but has no impact when the state is the largest shareholder.Theoretical Implications: Our study provides strong support for the argument that state ownership weakens corporate governance quality in partial privatization. It also demonstrates the contribution of the behavioral theory of organizational search to the study of top management turnover in emerging economies where it is difficult to identify forced turnover.Practical Implications: To further improve the economic performance of partially privatized firms, states should continue to dilute their ownership. In addition, firms should carefully manage top management turnover when performance is above target.
Business Group Affiliation, Firm Governance, and Firm Performance: Evidence from China and India
Authors: Singh Deeksha A. , Gaur Ajai S. 
Published: July 2009

ABSTRACTManuscript Type: EmpiricalResearch Question/Issue: This study seeks to understand how business group affiliation, within firm governance and external governance environment affect firm performance in emerging economies. We examine two aspects of within firm governance – ownership concentration and board independence.Research Findings/Insights: Using archival data on the top 500 Indian and Chinese firms from multiple data sources for 2007, we found that group affiliated firms performed worse than unaffiliated firms, and the negative relationship was stronger in the case of Indian firms than for Chinese firms. We also found that ownership concentration had a positive effect on firm performance, while board independence had a negative effect on firm performance. Further, we found that group affiliation – firm performance relationship in a given country context was moderated by ownership concentration.Theoretical/Academic Implications: This study utilizes an integration of agency theory with an institutional perspective, providing a more comprehensive framework to analyze the CG problems, particularly in the emerging economy firms. Empirically, our findings support, as well as contradict, some of the conventional wisdom, and suggest useful avenues for future research.Practitioner/Policy Implications: This study shows that reforms in general and CG reforms in particular are effective in emerging economies, which is an encouraging sign for policy makers. However, our research also suggests that it may be time for India and China to stop the encouragement for the empire building through group formation in the corporate world. For practioners, our findings suggest that firms need to balance the need for oversight with the need for advice, while selecting independent directors.
Non‐Tradable Share Reform and Corporate Governance in the Chinese Stock Market
Authors: Yeh Yin‐Hua , Shu Pei‐Gi , Lee Tsun‐Siou , Su Yu‐Hui 
Published: July 2009

ABSTRACTManuscript Type: EmpiricalResearch Question/Issue: Prior to China's split‐share structure reform, domestic A shares were divided into non‐tradable and tradable shares. Non‐tradable shareholders represent the government, hold roughly a two‐thirds majority, and manage the firms, while tradable shareholders have little power to affect the decisions made by non‐tradable shareholders. This is a typical structure to exhibit agency problems. The 2005 structure reform program stipulates that non‐tradable shareholders have to bargain with tradable shareholders in order to gain liquidity. The price that non‐tradable shareholders pay to tradable shareholders for gaining liquidity is defined as “compensation.” We explore the issue of why corporate governance might play an important role in affecting the level of compensation.Research Findings/Insights: Firms with a weak governance structure or severe agency problems are required to have a higher level of compensation. The level of compensation is positively correlated with the non‐tradable shareholding, the pledge ratio, and related‐party transactions, and is negatively correlated with foreign shareholdings. The same set of variables dictates the ex‐post wealth effect of tradable shareholders, but in the reverse direction.Theoretical/Academic Implications: The share reform provides a natural setting that allows tradable shareholders to reflect their concerns with agency problems. The mechanism could ameliorate the agency problems. Corporate governance, in a broad sense, is related to compensation and the ex‐post wealth effect of tradable shares.Practitioner/Policy Implications: A successful mechanism should be designed to have minority shareholders involved in the process and have the final compensation reflect the quality of corporate governance.