bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fine structure of hippocampal mossy fiber synapses following rapid high‐pressure freezing
Authors: Zhao Shanting , Studer Daniel , Graber Werner , Nestel Sigrun , Frotscher Michael 
Published: May 2012

SummarySynapses of hippocampal neurons play important roles in learning and memory processes and are involved in aberrant hippocampal function in temporal lobe epilepsy. Major neuronal types in the hippocampus as well as their input and output synapses are well known, but it has remained an open question to what extent conventional electron microscopy (EM) has provided us with the real appearance of synaptic fine structure under in vivo conditions. There is reason to assume that conventional aldehyde fixation and dehydration lead to protein denaturation and tissue shrinkage, likely associated with the occurrence of artifacts. However, realistic fine‐structural data of synapses are required for our understanding of the transmission process and for its simulation. Here, we used high‐pressure freezing and cryosubstitution of hippocampal tissue that was not subjected to aldehyde fixation and dehydration in ethanol to monitor the fine structure of an identified synapse in the hippocampal CA3 region, that is, the synapse between granule cell axons, the mossy fibers, and the proximal dendrites of CA3 pyramidal neurons. Our results showed that high‐pressure freezing nicely preserved ultrastructural detail of this particular synapse and allowed us to study rapid structural changes associated with synaptic plasticity.
Mossy cell dendritic structure quantified and compared with other hippocampal neurons labeled in rats in vivo
Authors: Buckmaster Paul S. 
Published: May 2012

SummaryMossy cells are likely to contribute to normal hippocampal function and to the pathogenesis of neurologic disorders that involve the hippocampus, including epilepsy. Mossy cells are the least well‐characterized excitatory neurons in the hippocampus. Their somatic and dendritic morphology has been described qualitatively but not quantitatively. In the present study rat mossy cells were labeled intracellularly with biocytin in vivo. Somatic and dendritic structure was reconstructed three‐dimensionally. For comparison, granule cells, CA3 pyramidal cells, and CA1 pyramidal cells were labeled and analyzed using the same approach. Among the four types of hippocampal neurons, granule cells had the smallest somata, fewest primary dendrites and dendritic branches, and shortest total dendritic length. CA1 pyramidal cells had the most dendritic branches and longest total dendritic length. Mossy cells and CA3 pyramidal cells both had large somata and similar total dendritic lengths. However, mossy cell dendrites branched less than CA3 pyramidal cells, especially close to the soma. These findings suggest that mossy cells have dendritic features that are not identical to any other type of hippocampal neuron. Therefore, electrotonic properties that depend on soma‐dendritic structure are likely to be distinct in mossy cells compared to other neurons.
Optical imaging of visual cortex epileptic foci and propagation pathways
Authors: Haglund Michael M. 
Published: May 2012

SummaryPrecise localization of neocortical epileptic foci is a complex problem that usually requires ictal video–electroencephalography (EEG) recordings; high‐resolution magnetic resonance imaging (MRI), positron emission tomography (PET), and single photon emission computed tomography (SPECT) studies; and/or invasive monitoring with implanted grid array electrodes. The exact ictal‐onset site must be identified and removed to obtain the best opportunity for a seizure‐free outcome. The goal of this study was to determine if high‐resolution optical imaging could precisely identify neocortical epileptic foci and what role underlying neuroanatomic pathways played in the seizure propagation. Small acute epileptic foci (0.5 × 0.5 mm2) were created in the primate visual neocortex and single‐unit and surface EEG recordings were combined with optical imaging of voltage‐sensitive dye changes. Brief visual stimulation was used to evoke interictal bursts. In addition, different visually evoked epileptiform bursts were analyzed to determine the location of the epileptic focus. Spike‐triggered averaging of the optical images associated with the surface EEG interictal bursts were analyzed to determine the exact location of the epileptic focus. Specific orientations of brief visual stimulation evoked different intensity optical changes and precisely localized the epileptic focus. Optical imaging identified individual epileptic foci that were <3 mm apart. The development of individual epileptic focus was monitored with optical imaging, which demonstrated excitatory activity at the focus with a surrounding zone of inhibitory‐like activity. Propagation pathways outside of the inhibitory‐like surround demonstrated alternating bands of excitation and inhibition with a pattern orthogonal to the ocular dominance columns. This experimental study demonstrates that optical imaging can precisely localize an epileptic focus, and provides excellent spatial resolution of the changes that occur in and around the site of the epileptic focus.
Impact of seizures on developing dendrites: Implications for intellectual developmental disabilities
Authors: Casanova Jose R. , Nishimura Masataka , Owens James W. , Swann John W. 
Published: May 2012

SummaryChildhood epilepsy can be severe and even catastrophic. In these instances, cognition can be impaired—leading to long‐term intellectual disabilities. One factor that could potentially cause cognitive deficits is the frequent seizures that characterize intractable epilepsy. However, it has been difficult to separate the effects seizures may have from those of preexisting neuropathologies and/or the effects of ongoing anticonvulsant therapies. Therefore, important questions are: Do early life seizures produce the learning deficits? And if they do, how do they do it? Results from recent animal models studies reviewed here show that recurrent seizures in infancy stop the growth of CA1 hippocampal dendrites. We speculate that the molecular mechanisms responsible for seizure‐induced growth suppression are homeostatic/neuroprotective, used by the developing nervous system in an attempt to limit neuronal and network excitability and prevent the continued generation of seizures. However, by preventing the normal growth of dendrites, there is a reduction in CA1 glutamatergic synapses that supports long‐lasting forms of synaptic plasticity thought to be the cellular basis of learning and memory. Therefore, dendrite growth suppression would reduce the neuroanatomic substrates for learning and memory, and in so doing could contribute in important ways to spatial learning and memory deficits that may be relevant to the cognitive deficits associated with childhood epilepsy.
Acute, but reversible, kainic acid–induced DNA damage in hippocampal CA1 pyramidal cells of p53‐deficient mice
Authors: Kinoshita Yoshito , Jürgen Wenzel H. , Kinoshita Chizuru , Schwartzkroin Philip A. , Morrison Richard S. 
Published: May 2012

Summaryp53 plays an essential role in mediating apoptotic responses to cellular stress, especially DNA damage. In a kainic acid (KA)–induced seizure model in mice, hippocampal CA1 pyramidal cells undergo delayed neuronal death at day 3–4 following systemic KA administration. We previously demonstrated that CA1 neurons in p53−/− animals are protected from such apoptotic neuronal loss. However, extensive morphological damage associated with DNA strand breaks in CA1 neurons was found in a fraction of p53−/− animals at earlier time points (8 h to 2 days). No comparable acute damage was observed in wild‐type animals. Stereological counting confirmed that there was no significant loss of CA1 pyramidal cells in p53−/− animals at 7 days post‐KA injection. These results suggest that seizure‐induced DNA strand breaks are accumulated to a greater extent but do not lead to apoptosis in the absence of p53. In wild‐type animals, therefore, p53 appears to stimulate DNA repair and also mediate apoptosis in CA1 neurons in this excitotoxicity model. These results also reflect remarkable plasticity of neurons in recovery from injury.
Quantitative trait locus on distal chromosome 1 regulates the occurrence of spontaneous spike‐wave discharges in DBA/2 mice
Authors: Bessaïh Thomas , de Yebenes Esther Garcia , Kirkland Kyle , Higley Michael J. , Buono Russell J. , Ferraro Thomas N. , Contreras Diego 
Published: May 2012

SummaryPurpose:  Most common forms of human epilepsy result from a complex combination of polygenetic and environmental factors. Quantitative trait locus (QTL) mapping is a first step toward the nonbiased discovery of epilepsy‐related candidate genes. QTL studies of susceptibility to induced seizures in mouse strains have consistently converged on a distal region of chromosome 1 as a major phenotypic determinant; however, its influence on spontaneous epilepsy remains unclear. In the present study we characterized the influence of allelic variations within this QTL, termed Szs1, on the occurrence of spontaneous spike‐wave discharges (SWDs) characteristic of absence seizures in DBA/2 (D2) mice.Methods:  We analyzed SWD occurrence and patterns in freely behaving D2, C57BL/6 (B6) and the congenic strains D2.B6‐Szs1 and B6.D2‐Szs1.Key Findings:  We showed that congenic manipulation of the Szs1 locus drastically reduced the number and the duration of SWDs in D2.B6‐Szs1 mice, which are homozygous for Szs1 from B6 strain on a D2 strain background. However, it failed to induce the full expression of SWDs in the reverse congenic animals B6.D2‐Szs1.Significance:  Our results demonstrate that the occurrence of SWDs in D2 animals is under polygenic control and, therefore, the D2 and B6 strains might be a useful model to dissect the genetic determinants of polygenic SWDs characteristic of typical absence seizures. Furthermore, we point to the existence of epistatic interactions between at least one modifier gene within Szs1 and genes within unlinked QTLs in regulating the occurrence of spontaneous nonconvulsive forms of epilepsies.
Music and epilepsy: A critical review
Authors: Maguire Melissa Jane 
Published: May 2012

SummaryThe effect of music on patients with epileptic seizures is complex and at present poorly understood. Clinical studies suggest that the processing of music within the human brain involves numerous cortical areas, extending beyond Heschl’s gyrus and working within connected networks. These networks could be recruited during a seizure manifesting as musical phenomena. Similarly, if certain areas within the network are hyperexcitable, then there is a potential that particular sounds or certain music could act as epileptogenic triggers. This occurs in the case of musicogenic epilepsy, whereby seizures are triggered by music. Although it appears that this condition is rare, the exact prevalence is unknown, as often patients do not implicate music as an epileptogenic trigger and routine electroencephalography does not use sound in seizure provocation. Music therapy for refractory epilepsy remains controversial, and further research is needed to explore the potential anticonvulsant role of music. Dopaminergic system modulation and the ambivalent action of cognitive and sensory input in ictogenesis may provide possible theories for the dichotomous proconvulsant and anticonvulsant role of music in epilepsy. The effect of antiepileptic drugs and surgery on musicality should not be underestimated. Altered pitch perception in relation to carbamazepine is rare, but health care professionals should discuss this risk or consider alternative medication particularly if the patient is a professional musician or native‐born Japanese. Studies observing the effect of epilepsy surgery on musicality suggest a risk with right temporal lobectomy, although the extent of this risk and correlation to size and area of resection need further delineation. This potential risk may bring into question whether tests on musical perception and memory should form part of the preoperative neuropsychological workup for patients embarking on surgery, particularly that of the right temporal lobe.
Corporate Governance and Capital Structure Dynamics
Authors: MORELLEC ERWAN , NIKOLOV BORIS , SCHÜRHOFF NORMAN 
Published: May 2012

ABSTRACTWe develop a dynamic tradeoff model to examine the importance of manager–shareholder conflicts in capital structure choice. In the model, firms face taxation, refinancing costs, and liquidation costs. Managers own a fraction of the firms’ equity, capture part of the free cash flow to equity as private benefits, and have control over financing decisions. Using data on leverage choices and the model's predictions for different statistical moments of leverage, we find that agency costs of 1.5% of equity value on average are sufficient to resolve the low‐leverage puzzle and to explain the dynamics of leverage ratios. Our estimates also reveal that agency costs vary significantly across firms and correlate with commonly used proxies for corporate governance.
The Real Effects of Financial Markets: The Impact of Prices on Takeovers
Authors: EDMANS ALEX , GOLDSTEIN ITAY , JIANG WEI 
Published: May 2012

ABSTRACTUsing mutual fund redemptions as an instrument for price changes, we identify a strong effect of market prices on takeover activity (the “trigger effect”). An interquartile decrease in valuation leads to a seven percentage point increase in acquisition likelihood, relative to a 6% unconditional takeover probability. Instrumentation addresses the fact that prices are endogenous and increase in anticipation of a takeover (the “anticipation effect”). Our results overturn prior literature that finds a weak relation between prices and takeovers without instrumentation. These findings imply that financial markets have real effects: They impose discipline on managers by triggering takeover threats.
Determinants of Cross‐Border Mergers and Acquisitions
Authors: EREL ISIL , LIAO ROSE C. , WEISBACH MICHAEL S. 
Published: May 2012

ABSTRACTThe vast majority of cross‐border mergers involve private firms outside of the United States. We analyze a sample of 56,978 cross‐border mergers between 1990 and 2007. We find that geography, the quality of accounting disclosure, and bilateral trade increase the likelihood of mergers between two countries. Valuation appears to play a role in motivating mergers: firms in countries whose stock market has increased in value, whose currency has recently appreciated, and that have a relatively high market‐to‐book value tend to be purchasers, while firms from weaker‐performing economies tend to be targets.
Threshold Events and Identification: A Study of Cash Shortfalls
Authors: BAKKE TOR‐ERIK , WHITED TONI M. 
Published: May 2012

ABSTRACTThreshold events are discrete events triggered when an observable continuous variable passes a known threshold. We demonstrate how to use threshold events as identification strategies by revisiting the evidence in Rauh (2006, Investment and financing constraints: Evidence from the funding of corporate pension plans, Journal of Finance 61, 33–71) that mandatory pension contributions cause investment declines. Rauh's result stems from heavily underfunded firms that constitute a small fraction of the sample and that differ sharply from the rest of the sample. To alleviate this issue, we use observations near funding thresholds and find causal effects of mandatory contributions on receivables, R&D, and hiring, but not on investment. We also provide useful suggestions and diagnostics for analyzing threshold events.
Investment, Idiosyncratic Risk, and Ownership
Authors: PANOUSI VASIA , PAPANIKOLAOU DIMITRIS 
Published: May 2012

ABSTRACTHigh‐powered incentives may induce higher managerial effort, but they also expose managers to idiosyncratic risk. If managers are risk averse, they might underinvest when firm‐specific uncertainty increases, leading to suboptimal investment decisions from the perspective of well‐diversified shareholders. We empirically document that, when idiosyncratic risk rises, firm investment falls, and more so when managers own a larger fraction of the firm. This negative effect of managerial risk aversion on investment is mitigated if executives are compensated with options rather than with shares or if institutional investors form a large part of the shareholder base.
CEO Compensation and Board Structure Revisited
Authors: GUTHRIE KATHERINE , SOKOLOWSKY JAN , WAN KAM‐MING 
Published: May 2012

ABSTRACTChhaochharia and Grinstein estimate that CEO pay decreases 17% more in firms that were not compliant with the recent NYSE/Nasdaq board independence requirement than in firms that were compliant. We document that 74% of this magnitude is attributable to two outliers of 865 sample firms. In addition, we find that the compensation committee independence requirement increases CEO total pay, particularly in the presence of effective shareholder monitoring. Our evidence casts doubt on the effectiveness of independent directors in constraining CEO pay as suggested by the managerial power hypothesis.
Low Proliferative Potential and Impaired Angiogenesis of Cultured Rat Kidney Endothelial Cells
Authors: BASILE DAVID P. , ZENG PINGYU , FRIEDRICH JESSICA L. , LEONARD ELLEN C. , YODER MERVIN C. 
Published: May 2012

Please cite this paper as: Basile DP, Zeng P, Friedrich JL, Leonard EC, Yoder MC. Low proliferative potential and impaired angiogenesis of cultured rat kidney endothelial cells. Microcirculation 19: 598–609, 2012.AbstractObjective:  CKD is histologically characterized by interstitial fibrosis, which may be driven by peritubular capillary dropout and hypoxia. Surprisingly, peritubular capillaries have little repair capacity. We sought to establish long‐term cultures of rat kidney endothelial cells to investigate their growth regulatory properties.Methods:  AKEC or YKEC were isolated using CD31‐based isolation techniques and sustained in long‐term cultures.Results:  Although YKEC grew slightly better than AKEC, both performed poorly compared with endothelial cells of the rat adult PMVEC, PAEC, or HUVEC cells. PMVEC and PAEC contained a large percentage of cells with high colony‐forming potential. In contrast, KECs were incapable of forming large colonies and most remained as single nondividing cells. KEC expressed high levels of mRNA for VEGF receptors, but were surprisingly insensitive to VEGF stimulation. KEC did not form branching structures on Matrigel when cultured alone, but in mixed cultures, KEC incorporated into branching structures with PMVEC.Conclusions:  These data suggest that the intrinsic growth of rat kidney endothelial cells is limited by unknown mechanisms. The low growth rate may be related to the minimal intrinsic regenerative capacity of renal capillaries.
A Concept of Thrombolysis as a Corrosion–Erosion Process Verified by Optical Microscopy
Authors: BAJD FRANCI , SERŠA IGOR 
Published: May 2012

Please cite this paper as: Bajd F, Serša I. A concept of thrombolysis as a corrosion–erosion process verified by optical microscopy. Microcirculation 19: 632–641, 2012.AbstractObjective:  Outcome of the thrombolytic treatment is dependent on biochemical reactions of the fibrinolytic system as well as on hemodynamic conditions. However, understanding of the interaction between these two processes is still deficient.Methods:  Model blood clot thrombolysis in an artificial perfusion system was studied by stroboscopic optical microscopy. The obtained images were analyzed by particle‐tracking software for clot size distributions of removed clot fragments, and for non‐lysed blood clot areas as function of time. Based on the experimental results, a probabilistic phenomenological model of blood clot dissolution was developed, in which mechanical forces of streaming plasma are in balance with binding forces of blood cells to the remaining clot.Results:  The clot dissolution rate and maximum size of removed clot fragments were increased with greater flow rate. A 3.3‐fold flow rate increase resulted in a two‐fold clot dissolution rate increase, while sizes of the removed fragments were in the range of single blood cells, up to thousand‐cell clusters. Our phenomenological microscale model of clot dissolution suggests that thrombolysis is a corrosion–erosion‐like process.Conclusions:  The findings of this study provide a possible explanation for the origin of clot fragment formation in the blood clot dissolution process.
Glycogen Accumulation and Degradation by the Trichomonads Trichomonas vaginalis and Trichomonas tenax
Authors: Nielsen Tyler J. , Pradhan Prajakta , Brittingham Andrew , Wilson Wayne A. 
Published: May 2012

AbstractSeveral species of trichomonad have been shown to accumulate significant quantities of glycogen during growth, suggesting an important role for this compound in cell physiology. We provide the first analysis of the changes in glycogen content and glycogen phosphorylase activity that occur during in vitro growth of two trichomonad species: Trichomonas vaginalis and Trichomonas tenax. Both species accumulated glycogen following inoculation into fresh medium and utilized this compound during logarithmic growth. Glycogen phosphorylase activity also varied during growth in a species‐specific manner. The expression of phosphorylase genes in T. vaginalis remained constant during growth and thus transcriptional control did not explain the observed fluctuations in phosphorylase activity. After cloning, expression, and purification, two recombinant glycogen phosphorylases from T. vaginalis and one recombinant glycogen phosphorylase from T. tenax had robust activity and, in contrast to many other eukaryotic glycogen phosphorylases, did not appear to be regulated by reversible protein phosphorylation. Furthermore, allosteric regulation, if present, was not mediated by compounds known to impact the activity of better characterized phosphorylases.
Local activation of cardiac stem cells for post‐myocardial infarction cardiac repair
Authors: Wen Zhuzhi , Mai Zun , Zhang Haifeng , Chen Yangxin , Geng Dengfeng , Zhou Shuxian , Wang Jingfeng 
Published: May 2012

AbstractThe prognosis of patients with myocardial infarction (MI) and resultant chronic heart failure remains extremely poor despite continuous advancements in optimal medical therapy and interventional procedures. Animal experiments and clinical trials using adult stem cell therapy following MI have shown a global improvement of myocardial function. The emergence of stem cell transplantation approaches has recently represented promising alternatives to stimulate myocardial regeneration. Regarding their tissue‐specific properties, cardiac stem cells (CSCs) residing within the heart have advantages over other stem cell types to be the best cell source for cell transplantation. However, time‐consuming and costly procedures to expanse cells prior to cell transplantation and the reliability of cell culture and expansion may both be major obstacles in the clinical application of CSC‐based transplantation therapy after MI. The recognition that the adult heart possesses endogenous CSCs that can regenerate cardiomyocytes and vascular cells has raised the unique therapeutic strategy to reconstitute dead myocardium via activating these cells post‐MI. Several strategies, such as growth factors, mircoRNAs and drugs, may be implemented to potentiate endogenous CSCs to repair infarcted heart without cell transplantation. Most molecular and cellular mechanism involved in the process of CSC‐based endogenous regeneration after MI is far from understanding. This article reviews current knowledge opening up the possibilities of cardiac repair through CSCs activation in situ in the setting of MI.