bluuebunny/crossref_metadata_2025 huggingface dataset:
Extracellular Spermine Exacerbates Ischemic Neuronal Injury through Sensitization of ASIC1a Channels to Extracellular Acidosis
Authors: Duan Bo , Wang Yi-Zhi , Yang Tao , Chu Xiang-Ping , Yu Ye , Huang Yu , Cao Hui , Hansen Jillian , Simon Roger P. , Zhu Michael X. , Xiong Zhi-Gang , Xu Tian-Le
Published: February 2011

Ischemic brain injury is a major problem associated with stroke. It has been increasingly recognized that acid-sensing ion channels (ASICs) contribute significantly to ischemic neuronal damage, but the underlying mechanism has remained elusive. Here, we show that extracellular spermine, one of the endogenous polyamines, exacerbates ischemic neuronal injury through sensitization of ASIC1a channels to extracellular acidosis. Pharmacological blockade of ASIC1a or deletion of theASIC1gene greatly reduces the enhancing effect of spermine in ischemic neuronal damage both in cultures of dissociated neurons and in a mouse model of focal ischemia. Mechanistically, spermine profoundly reduces desensitization of ASIC1a by slowing down desensitization in the open state, shifting steady-state desensitization to more acidic pH, and accelerating recovery between repeated periods of acid stimulation. Spermine-mediated potentiation of ASIC1a activity is occluded by PcTX1 (psalmotoxin 1), a specific ASIC1a inhibitor binding to its extracellular domain. Functionally, the enhanced channel activity is accompanied by increased acid-induced neuronal membrane depolarization and cytoplasmic Ca2+overload, which may partially explain the exacerbated neuronal damage caused by spermine. More importantly, blocking endogenous spermine synthesis significantly attenuates ischemic brain injury mediated by ASIC1a but not that by NMDA receptors. Thus, extracellular spermine contributes significantly to ischemic neuronal injury through enhancing ASIC1a activity. Our data suggest new neuroprotective strategies for stroke patients via inhibition of polyamine synthesis and subsequent spermine–ASIC interaction.
Cerebellar Plasticity and the Automation of First-Order Rules
Authors: Balsters Joshua H. , Ramnani Narender
Published: February 2011

Theories of corticocerebellar function propose roles for the cerebellum in automating motor control, a process thought to depend on plasticity in cerebellar circuits that exchange information with the motor cortex. Little is known, however, about automating behaviors beyond the motor domain. The present study tested the hypothesis that cerebellar plasticity also subserves the development of automaticity in behavior based on low-order rules. Human subjects were required to learn two sets of first-order rules in which visual stimuli of different shapes each arbitrarily instructed a particular finger movement. We used event-related functional magnetic resonance imaging to scan subjects while these response rules became increasingly automatic with practice, as assessed with a dual-task procedure. We found that the amplitude of the blood oxygenation level-dependent signal gradually decreased as a function of practice, as responses became increasingly automatic, and that this effect was greater for a set of rules that became automatic rapidly compared with a second set, which became automatic more slowly. These trial-by-trial activity changes occurred in Crus I of cerebellar cortical lobule HVIIA, in which neurons exchange information with the prefrontal cortex rather than the motor cortex. Activity in Crus I was time locked specifically to the processing of these rules, rather than to subsequent actions. The results support the hypothesis that decreases in cerebellar cortical activity underlie the automation of behavior, whether related to motor control and motor cortex or to response rules and prefrontal cortex.
Actin Polymerization Is Essential for Myelin Sheath Fragmentation during Wallerian Degeneration
Authors: Jung Junyang , Cai Wenting , Lee Hyun Kyoung , Pellegatta Marta , Shin Yoon Kyung , Jang So Young , Suh Duk Joon , Wrabetz Lawrence , Feltri M. Laura , Park Hwan Tae
Published: February 2011

The mechanisms that trigger Wallerian degeneration (WD) of peripheral nerves after injury are not well understood. During the early period of WD, fragmentation of myelin into ovoid structures occurs near the Schmidt-Lantermann incisures (SLI), a noncompact region of the myelin sheath containing autotypical adherens junction. In this study, we found that new filamentous actin polymerization occurs in the SLI of mouse sciatic nerves after injury and that its inhibition prevented not only the degradation of E-cadherin in the SLI but also myelin ovoid formation. However, the inhibition of actin polymerization could not block Schwann cell dedifferentiation. The activation of Rac GTPase was observed in the distal stump of the injured nerves, and a specific Rac inhibitor, a dominant-negative Rac, and Rac1-RNA interference blocked myelin ovoid formation. Together, these findings suggest that dynamic changes in actin in the SLI are essential for initiation of demyelination after peripheral nerve injury.
Inhibition of Amyloid-β (Aβ) Peptide-Binding Alcohol Dehydrogenase-Aβ Interaction Reduces Aβ Accumulation and Improves Mitochondrial Function in a Mouse Model of Alzheimer's Disease
Authors: Yao Jun , Du Heng , Yan Shiqiang , Fang Fang , Wang Chaodong , Lue Lih-Fen , Guo Lan , Chen Doris , Stern David M. , Gunn Moore Frank J. , Xi Chen John , Arancio Ottavio , Yan Shirley ShiDu
Published: February 2011

Amyloid-β (Aβ) peptide-binding alcohol dehydrogenase (ABAD), an enzyme present in neuronal mitochondria, exacerbates Aβ-induced cell stress. The interaction of ABAD with Aβ exacerbates Aβ-induced mitochondrial and neuronal dysfunction. Here, we show that inhibition of the ABAD-Aβ interaction, using a decoy peptide (DP)in vitroandin vivo, protects against aberrant mitochondrial and neuronal function and improves spatial learning/memory. Intraperitoneal administration of ABAD-DP [fused to the transduction of human immunodeficiency virus 1-transactivator (Tat) protein and linked to the mitochondrial targeting sequence (Mito) (TAT-mito-DP) to transgenic APP mice (Tg mAPP)] blocked formation of ABAD-Aβ complex in mitochondria, increased oxygen consumption and enzyme activity associated with the mitochondrial respiratory chain, attenuated mitochondrial oxidative stress, and improved spatial memory. Similar protective effects were observed in Tg mAPP mice overexpressing neuronal ABAD decoy peptide (Tg mAPP/mito-ABAD). Notably, inhibition of the ABAD-Aβ interaction significantly reduced mitochondrial Aβ accumulation. In parallel, the activity of mitochondrial Aβ-degrading enzyme PreP (presequence peptidase) was enhanced in Tg mAPP mitochondria expressing the ABAD decoy peptide. These data indicate that segregating ABAD from Aβ protects mitochondria/neurons from Aβ toxicity; thus, ABAD-Aβ interaction is an important mechanism underlying Aβ-mediated mitochondrial and neuronal perturbation. Inhibitors of ABAD-Aβ interaction may hold promise as targets for the prevention and treatment of Alzheimer's disease.
Nonuniform High-Gamma (60–500 Hz) Power Changes Dissociate Cognitive Task and Anatomy in Human Cortex
Authors: Gaona Charles M. , Sharma Mohit , Freudenburg Zachary V. , Breshears Jonathan D. , Bundy David T. , Roland Jarod , Barbour Dennis L. , Schalk Gerwin , Leuthardt Eric C.
Published: February 2011

High-gamma-band (>60 Hz) power changes in cortical electrophysiology are a reliable indicator of focal, event-related cortical activity. Despite discoveries of oscillatory subthreshold and synchronous suprathreshold activity at the cellular level, there is an increasingly popular view that high-gamma-band amplitude changes recorded from cellular ensembles are the result of asynchronous firing activity that yields wideband and uniform power increases. Others have demonstrated independence of power changes in the low- and high-gamma bands, but to date, no studies have shown evidence of any such independence above 60 Hz. Based on nonuniformities in time-frequency analyses of electrocorticographic (ECoG) signals, we hypothesized that induced high-gamma-band (60–500 Hz) power changes are more heterogeneous than currently understood. Using single-word repetition tasks in six human subjects, we showed that functional responsiveness of different ECoG high-gamma sub-bands can discriminate cognitive task (e.g., hearing, reading, speaking) and cortical locations. Power changes in these sub-bands of the high-gamma range are consistently present within single trials and have statistically different time courses within the trial structure. Moreover, when consolidated across all subjects within three task-relevant anatomic regions (sensorimotor, Broca's area, and superior temporal gyrus), these behavior- and location-dependent power changes evidenced nonuniform trends across the population. Together, the independence and nonuniformity of power changes across a broad range of frequencies suggest that a new approach to evaluating high-gamma-band cortical activity is necessary. These findings show that in addition to time and location, frequency is another fundamental dimension of high-gamma dynamics.
Rapamycin Suppresses Mossy Fiber Sprouting But Not Seizure Frequency in a Mouse Model of Temporal Lobe Epilepsy
Authors: Buckmaster Paul S. , Lew Felicia H.
Published: February 2011

Temporal lobe epilepsy is prevalent and can be difficult to treat effectively. Granule cell axon (mossy fiber) sprouting is a common neuropathological finding in patients with mesial temporal lobe epilepsy, but its role in epileptogenesis is unclear and controversial. Focally infused or systemic rapamycin inhibits the mammalian target of rapamycin (mTOR) signaling pathway and suppresses mossy fiber sprouting in rats. We tested whether long-term systemic treatment with rapamycin, beginning 1 d after pilocarpine-induced status epilepticus in mice, would suppress mossy fiber sprouting and affect the development of spontaneous seizures. Mice that had experienced status epilepticus and were treated for 2 months with rapamycin displayed significantly less mossy fiber sprouting (42% of vehicle-treated animals), and the effect was dose dependent. However, behavioral and video/EEG monitoring revealed that rapamycin- and vehicle-treated mice displayed spontaneous seizures at similar frequencies. These findings suggest mossy fiber sprouting is neither pro- nor anti-convulsant; however, there are caveats. Rapamycin treatment also reduced epilepsy-related hypertrophy of the dentate gyrus but did not significantly affect granule cell proliferation, hilar neuron loss, or generation of ectopic granule cells. These findings are consistent with the hypotheses that hilar neuron loss and ectopic granule cells might contribute to temporal lobe epileptogenesis.
Fine Spatial Information Represented in a Population of Retinal Ganglion Cells
Authors: Soo Frederick S. , Schwartz Gregory W. , Sadeghi Kolia , Berry Michael J.
Published: February 2011

Detailed measurement of ganglion cell receptive fields often reveals significant deviations from a smooth, Gaussian profile. We studied the effect of these irregularities on the representation of fine spatial information in the retina. We recorded from nearby clusters of ganglion cells, testing their ability to determine the location of small flashed spots, and we compared the results to the prediction of a Gaussian receptive field model derived from reverse correlation. Despite considerable receptive field overlap, almost all ganglion cell pairs signaled nearly independently. For groups of five cells with highly overlapping receptive fields, the measured light-evoked currents encoded ∼33% more information than predicted by the Gaussian receptive field model. Including measured local irregularities in the receptive field model increased performance to the level observed experimentally. These results suggest that instead of being an unavoidable defect, irregularities may be a positive design feature of population neural codes.
The UNC5C Netrin Receptor Regulates Dorsal Guidance of Mouse Hindbrain Axons
Authors: Kim Doyeun , Ackerman Susan L.
Published: February 2011

The cerebellum receives its input from multiple precerebellar nuclei located in the brainstem and sends processed information to other brain structures via the deep cerebellar neurons. Guidance molecules that regulate the complex migrations of precerebellar neurons and the initial guidance of their leading processes have been identified. However, the molecules necessary for dorsal guidance of precerebellar axons to the developing cerebellum or for guidance of decussating axons of the deep nuclei are not known. To determine whetherUnc5cplays a role in the dorsal guidance of precerebellar and deep cerebellar axons, we studied axonal trajectories of these neurons inUnc5c−/−mice. Our results show thatUnc5cis expressed broadly in the precerebellar and deep cerebellar neurons.Unc5cdeletion disrupted long-range dorsal guidance of inferior olivary and pontine axons after crossing the midline. In addition, dorsal guidance of the axons from the medial deep cerebellar and external cuneate neurons was affected inUnc5c−/−mice, as were anterior migrations of pontine neurons. Coincident with the guidance defects of their axons, degeneration of neurons in the external cuneate nucleus and subdivisions of the inferior olivary nucleus was observed inUnc5c−/−mice. Lastly, transgenic expression ofUnc5cin deep neurons and pontine neurons by theAtoh1promoter rescued defects of the medial deep cerebellar and pontine axons observed inUnc5c−/−embryos, demonstrating thatUnc5cacts cell autonomously in the guidance of these axons. Our results suggest thatUnc5cplays a broad role in dorsal guidance of axons in the developing hindbrain.
Infragranular Sources of Sustained Local Field Potential Responses in Macaque Primary Visual Cortex
Authors: Maier Alexander , Aura Christopher J. , Leopold David A.
Published: February 2011

A local field potential (LFP) response can be measured throughout the visual cortex in response to the abrupt appearance of a visual stimulus. Averaging LFP responses to many stimulus presentations isolates transient, phase-locked components of the response that are consistent from trial to trial. However, stimulus responses are also composed of sustained components, which differ in their phase from trial to trial and therefore must be evaluated using other methods, such as computing the power of the response of each trial before averaging. Here, we investigate the basis of phase-locked and non-phase-locked LFP responses in the primary visual cortex of the macaque monkey using a novel variant of current source density (CSD) analysis. We applied a linear array of electrode contacts spanning the thickness of the cortex to measure the LFP and compute band-limited CSD power to identify the laminar sites of persistent current exchange that may be the basis of sustained visual LFP responses. In agreement with previous studies, we found a short-latency phase-locked current sink, thought to correspond to thalamocortical input to layer 4C. In addition, we found a prominent non-phase-locked component of the CSD that persisted as long as the stimulus was physically present. The latter was relatively broadband, lasted throughout the stimulus presentation, and was centered ∼500 μm deeper than the initial current sink. These findings demonstrate a fundamental difference in the neural mechanisms underlying the initial and sustained processing of simple visual stimuli in the V1 microcircuit.
Region-Specific Involvement of BDNF Secretion and Synthesis in Conditioned Taste Aversion Memory Formation
Authors: Ma Ling , Wang Dong-Dong , Zhang Tian-Yi , Yu Hui , Wang Yue , Huang Shu-Hong , Lee Francis S. , Chen Zhe-Yu
Published: February 2011

Brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin-related kinase receptor B (TrkB), play a critical role in activity-dependent plasticity processes such as long-term potentiation, learning, and memory. It has been shown that BDNF exerts different or even opposite effects on behavior depending on the neural circuit. However, the detailed role of BDNF in memory process on the basis of its location has not been fully understood. Here, we aim to investigate the regional specific involvement of BDNF/TrkB in hippocampal-independent conditioned taste aversion (CTA) memory processes. We found region-specific changes in BDNF expression during CTA learning. CTA conditioning induced increased BDNF levels in the central nuclei of amygdala (CeA) and insular cortex, but not in the basolateral amygdala (BLA) and ventromedial prefrontal cortex. Interestingly, we found that the enhanced TrkB phosphorylation occurred at the time point before the increased BDNF expression, suggesting rapid induction of activity-dependent BDNF secretion by CTA learning. Moreover, targeted infusion of BDNF antibodies or BDNF antisense oligonucleotides revealed that activity-dependent BDNF secretion and synthesis in the CeA, but not the BLA, was respectively involved in the short- and long-term memory formation of CTA. Finally, we found that infusion of exogenous BDNF into the CeA could enhance CTA learning. These data suggest that region-specific BDNF release and synthesis temporally regulate different CTA memory phases through activation of TrkB receptors.
Dual Encoding of Muscle Tension and Eye Position by Abducens Motoneurons
Authors: Davis-López de Carrizosa María A. , Morado-Díaz Camilo J. , Miller Joel M. , de la Cruz Rosa R. , Pastor Ángel M.
Published: February 2011

Extraocular muscle tension associated with spontaneous eye movements has a pulse-slide-step profile similar to that of motoneuron firing rate. Existing models only relate motoneuron firing to eye position, velocity and acceleration. We measured and quantitatively compared lateral rectus muscle force and eye position with the firing of abducens motoneurons in the cat to determine fundamental encoding correlations. During fixations (step), muscle force increased exponentially with eccentric eye position, consistent with a model of estimate ensemble motor innervation based on neuronal sensitivities and recruitment order. Moreover, firing rate in all motoneurons tested was better related to eye position than to muscle tension during fixations. In contrast, during the postsaccadic slide phase, the time constant of firing rate decay was closely related to that of muscle force decay, suggesting that all motoneurons encode muscle tension as well. Discharge characteristics of abducens motoneurons formed overlapping clusters of phasic and tonic motoneurons, thus, tonic units recruited earlier and had a larger slide signal. We conclude that the slide signal is a discharge characteristic of the motoneuron that controls muscle tension during the postsaccadic phase and that motoneurons are specialized for both tension and position-related properties. The organization of signal content in the pool of abducens motoneurons from the very phasic to the very tonic units is possibly a result of the differential trophic background received from distinct types of muscle fibers.
Two Layers of Synaptic Processing by Principal Neurons in Piriform Cortex
Authors: Suzuki Norimitsu , Bekkers John M.
Published: February 2011

The primary olfactory (or piriform) cortex is a trilaminar paleocortex that is thought to construct unified “odor images” from the odor components identified by the olfactory bulb. How the piriform cortex (PC) accomplishes this sophisticated synthetic task, despite its relatively simple architecture, is unknown. Here we usedin vitropatch-clamp recordings from acute slices of the anterior PC of mice to identify microcircuits involved in excitatory synaptic processing. Cluster analysis confirmed the presence of two prominent classes of glutamatergic principal cells in the main input layer (layer II) of the PC: semilunar (SL) cells and superficial pyramidal (SP) cells. SL cells received stronger afferent excitatory input from the olfactory bulb, on average, than did SP cells. This was due to the larger mean strength of single-fiber afferents onto SL cells. In contrast, SP cells received stronger associational (intracortical) excitatory inputs, most likely due to their more extensive dendritic trees within the associational layers. Tissue-cut experiments and dual recordings from SL and SP cells in disinhibited slices were consistent with the distinctive patterns of connectivity of these two cell classes. Our findings suggest that the anterior PC employs at least two layers of excitatory synaptic processing: one involving strong afferent inputs onto SL cells, and another involving strong intracortical inputs onto SP cells. This architecture may allow the PC to sequentially process olfactory information within segregated subcircuits.
Role of Extracellular Signal-Regulated Kinase in Synaptic Transmission and Plasticity of a Nociceptive Input on Capsular Central Amygdaloid Neurons in Normal and Acid-Induced Muscle Pain Mice
Authors: Cheng Sin-Jhong , Chen Chien-Chang , Yang Hsiu-Wen , Chang Ya-Ting , Bai Shin-Wen , Chen Chih-Cheng , Yen Chen-Tung , Min Ming-Yuan
Published: February 2011

Application of phorbol 12,13-diacetate (PDA) caused marked enhancement of synaptic transmission of nociceptive parabrachio-amygdaloid (PBA) input onto neurons of the capsular central amygdaloid (CeAC) nucleus. The potentiation of PBA–CeAC EPSCs by PDA involved a presynaptic protein kinase C (PKC)-dependent component and a postsynaptic PKC–extracellular-regulated kinase (ERK)-dependent component. NMDA glutamatergic receptor (NMDAR)-dependent long-term potentiation (LTP) of PBA–CeAC EPSCs, which was also dependent on the PKC–ERK signaling pathway, was induced by tetanus stimulation at 100 Hz. In slices from mice subjected to acid-induced muscle pain (AIMP), phosphorylated ERK levels in the CeAC increased, and PBA–CeAC synaptic transmission was postsynaptically enhanced. The enhanced PBA–CeAC synaptic transmission in AIMP mice shared common mechanisms with the postsynaptic potentiation effect of PDA and induction of NMDAR-dependent LTP by high-frequency stimulation in normal slices, both of which required ERK activation. Since the CeAC plays an important role in the emotionality of pain, enhanced synaptic function of nociceptive (PBA) inputs onto CeAC neurons might partially account for the supraspinal mechanisms underlying central sensitization.
Orienting Attention to an Upcoming Tactile Event Involves a Spatially and Temporally Specific Modulation of Sensorimotor Alpha- and Beta-Band Oscillations
Authors: van Ede Freek , de Lange Floris , Jensen Ole , Maris Eric
Published: February 2011

Our perception is facilitated if we know where and when a sensory stimulus will occur. This phenomenon is accounted for by spatial and temporal orienting of attention. Whereas spatial orienting of attention has repeatedly been shown to involve spatially specific modulations of ongoing oscillations within sensory cortex, it is not clear to what extent anticipatory modulations of ongoing oscillations are involved in temporal orienting of attention. To address this, we recorded magnetoencephalography while human participants performed a tactile discrimination task. We cued participants to the left or the right hand, after which a tactile stimulus was presented at one of several fixed temporal delays. We thus assessed whether and how ongoing sensorimotor oscillations are modulated during tactile anticipation. We provide evidence for three phenomena. First, orienting to an upcoming tactile event involves a spatially specific contralateral suppression of alpha- and beta-band oscillations within sensorimotor cortex. Second, this modulation is deployed with temporal specificity, and this is more pronounced for beta-band compared with alpha-band oscillations. Third, the contralateral suppression of beta-band oscillations is associated with faster responses to subsequently presented tactile stimuli. Control measures showed that these results cannot be explained by motor planning or execution. We conclude that the modulation of ongoing oscillations within sensory cortex reflects a unifying mechanism underlying both spatial and temporal orienting of attention.
PICK1 Loss of Function Occludes Homeostatic Synaptic Scaling
Authors: Anggono Victor , Clem Roger L. , Huganir Richard L.
Published: February 2011

Homeostatic synaptic scaling calibrates neuronal excitability by adjusting synaptic strengths during prolonged changes in synaptic activity. The molecular mechanisms that regulate the trafficking of AMPA receptors (AMPARs) during synaptic scaling are largely unknown. Here, we show that chronic activity blockade reduces PICK1 protein level on a time scale that coincides with the accumulation of surface AMPARs. PICK1 loss of function alters the subunit composition and the abundance of GluA2-containing AMPARs. Due to aberrant trafficking of these receptors, the increase in synaptic strength in response to synaptic inactivity is occluded in neurons generated from PICK1 knock-out mouse. In agreement with electrophysiological recordings, no defect of AMPAR trafficking is observed in PICK1 knock-out neurons in response to elevated neuronal activity. Overall, our data reveal an important role of PICK1 in inactivity-induced synaptic scaling by regulating the subunit composition, abundance, and trafficking of GluA2-containing AMPARs.
α-Synuclein Negatively Regulates Protein Kinase Cδ Expression to Suppress Apoptosis in Dopaminergic Neurons by Reducing p300 Histone Acetyltransferase Activity
Authors: Jin Huajun , Kanthasamy Arthi , Ghosh Anamitra , Yang Yongjie , Anantharam Vellareddy , Kanthasamy Anumantha G.
Published: February 2011

We recently demonstrated that protein kinase Cδ (PKCδ), an important member of the novel PKC family, is a key oxidative stress-sensitive kinase that can be activated by caspase-3-dependent proteolytic cleavage to induce dopaminergic neuronal cell death. We now report a novel association between α-synuclein (αsyn), a protein associated with the pathogenesis of Parkinson's disease, and PKCδ, in which αsyn negatively modulates the p300- and nuclear factor-κB (NFκB)-dependent transactivation to downregulate proapoptotic kinase PKCδ expression and thereby protects against apoptosis in dopaminergic neuronal cells. Stable expression of human wild-type αsyn at physiological levels in dopaminergic neuronal cells resulted in an isoform-dependent transcriptional suppression of PKCδ expression without changes in the stability of mRNA and protein or DNA methylation. The reduction in PKCδ transcription was mediated, in part, through the suppression of constitutive NFκB activity targeted at two proximal PKCδ promoter κB sites. This occurred independently of NFκB/IκBα (inhibitor of κBα) nuclear translocation but was associated with decreased NFκB-p65 acetylation. Also, αsyn reduced p300 levels and its HAT (histone acetyltransferase) activity, thereby contributing to diminished PKCδ transactivation. Importantly, reduced PKCδ and p300 expression also were observed within nigral dopaminergic neurons in αsyn-transgenic mice. These findings expand the role of αsyn in neuroprotection by modulating the expression of the key proapoptotic kinase PKCδ in dopaminergic neurons.
Differential responses to salt supplementation in adult male and female rat adrenal glands following intrauterine growth restriction
Authors: Bibeau Karine , Otis Mélissa , St-Louis Jean , Gallo-Payet Nicole , Brochu Michèle
Published: February 2011

In low sodium-induced intrauterine growth restricted (IUGR) rat, foetal adrenal steroidogenesis as well as the adult renin–angiotensin–aldosterone system (RAAS) is altered. The aim of the present study was to determine the expression of cytochrome P450 aldosterone synthase (P450aldo) and of angiotensin II receptor subtypes 1 (AT1R) and 2 (AT2R) in adult adrenal glands and whether this expression could be influenced by IUGR and by high-salt intake in a sex-specific manner. After 6 weeks of 0.9% NaCl supplementation, plasma renin activity, P450aldo expression and serum aldosterone levels were decreased in all groups. In males, IUGR induced an increase in AT1R, AT2R, and P450aldo levels, without changes in morphological appearance of the zona glomerulosa (ZG). By contrast, in females, IUGR had no effect on the expression of AT1R, but increased AT2R mRNA while decreasing protein expression of AT2R and P450aldo. In males, salt intake in IUGR rats reduced both AT1R mRNA and protein, while for AT2R, mRNA levels decreased whereas protein expression increased. In females, salt intake reduced ZG size in IUGR but had no affect on AT1R or AT2R expression in either group. These results indicate that, in response to IUGR and subsequently to salt intake, P450aldo, AT1R, and AT2R levels are differentially expressed in males and females. However, despite these adrenal changes, adult IUGR rats display adequate physiological and adrenal responses to high-salt intake, via RAAS inhibition, thus suggesting that extra-adrenal factors likely compensate for ZG alterations induced by IUGR.
Pós-graduação do Instituto Nacional de Pesquisas Espaciais numa perspectiva de gênero
Authors: Moreira Maria Lígia , Velho Lea
Published: February 2011

Este trabalho tem como objetivo traçar um quadro da inserção das mulheres nos cursos de pós-graduação desenvolvidos pelo Instituto Nacional de Pesquisas Espaciais. Através de entrevistas com as egressas, são apresentadas as motivações que as levaram a escolher os cursos oferecidos e de que modo, segundo elas, estes contribuíram para as suas carreiras profissionais em uma área ainda considerada masculina - a área espacial.
The Mutual Fund—An Institutional Investor that Acts Like an Individual
Authors: Usrey Spencer , Schnee Edward , Taylor Gary
Published: February 2011

ABSTRACT: We examine changes in the average mutual fund’s investments following the Jobs and Growth Tax Relief Reconciliation Act of 2003 (JGTRR). The JGTRR decreased the tax penalty on dividend and capital gains income. We hypothesize that mutual fund managers will respond to the investment preferences of the underlying shareholders and increase their ownership of dividend-paying firms. We present evidence supporting the hypothesis that mutual fund managers increased their ownership of dividend-paying firms following the JGTRR. However, we do not find evidence that the investment managers of other institutional investors increased their ownership of dividend-paying firms following the JGTRR. These results indicate that mutual funds are influenced by the tax preferences of their underlying investors, form tax clienteles, and exhibit different investment policies when compared to other types of institutional investors.
Empirical Evidence on the Impact of Book-Tax Differences on Divergence of Opinion among Investors
Authors: Comprix Joseph , Graham Roger C. , Moore Jared A.
Published: February 2011

ABSTRACT: It is well known that the objectives of financial accounting and tax accounting sometimes conflict, resulting in book-tax differences (BTDs). In this study we test for associations between measures of BTDs and measures of market participants’ uncertainty regarding the information conveyed in financial reports. The measures of market participant uncertainty are: (1) share turnover, (2) analyst forecast dispersion, and (3) stock return variance. We find positive associations between levels and variability of total BTDs and the three measures. After disaggregating BTDs into their permanent and temporary components, we find that both are positively associated with market uncertainty, although the permanent component of BTDs is generally more strongly and consistently associated with measures of uncertainty than is the temporary component. We interpret these results, in part, as indicative of the possible effect of uncertainty contained in BTDs, especially permanent BTDs, on the precision of the information conveyed in the financial statements.
Tax-Motivated Increases in Qualifying Distributions by Private Foundations
Authors: Yoder Timothy R. , Addy Noel , McAllister Brian P.
Published: February 2011

ABSTRACT: We examine three categories of private foundations with tax incentives to increase their qualifying distributions: (1) foundations barely qualifying for the 1 percent tax rate on net investment income, (2) foundations barely avoiding the tax on undistributed income, and (3) foundations that pay an excise tax on undistributed income. We expect tax-motivated foundations to use allocations across expense categories and over time to increase their qualifying distributions. Our sample consists of a balanced panel of 1,974 private foundations over a 12-year period from 1995 through 2006, resulting in 23,688 foundation years. We find that foundations barely meeting the 1 percent tax benchmark use tax-motivated allocations both across expense categories and over time to increase qualifying distributions. In contrast, foundations barely avoiding or minimizing the tax on undistributed income use set-aside amounts to allocate distributions over time, but do not use allocations across expense categories to increase qualifying distributions.
Responses of Antarctic Tundra Ecosystem to Climate Change and Human Activity
Authors: Olech Maria
Published: February 2011

Over the last couple of years the Antarctic Peninsula region has been one of the fastest warming regions on the Earth. Rapidly proceeding deglaciation uncovers new areas for colonisation and formation of Antarctic tundra communities. The most evident dynamics, i.e. changes in both biodiversity and structure of tundra communities, are observed in the forefields of retreating glaciers. This paper presents examples of changes in biodiversity and in the direction and rate of succession changes taking place due to climate warming compounded by synanthropization in the maritime Antarctic
A Community Mental Health Service Delivery Model: Integrating the Evidence Base Within Existing Clinical Models
Authors: Flannery Frank , Adams Danielle , O'Connor Nick
Published: February 2011

Objectives: A model of care for community mental health services was developed by reviewing the available literature, surveying ‘best practice’ and evaluating the performance of existing services in a metropolitan area mental health service servicing a population of approximately 1.1 million people.

Methods: A review of relevant academic literature and recognized ‘good practice’ service delivery models was undertaken in conjunction with a review of local activity data and consultation with key stakeholders (not addressed in this paper). A model was developed identifying the core functions of community mental health service delivery.

Results: The components of a comprehensive, integrated model of community mental health service (CMHS) are outlined. The essential components of a comprehensive, integrated model of CMHSs include: acute and emergency response, community continuing care services, assertive rehabilitation teams, partnerships with general practitioners and other human services agencies.

Conclusions: We propose a comprehensive integrated model of community mental health service. Clarity of role, required outputs and expected outcomes will assist the development of effective and appropriate community mental health services. Outreach to the community is a key success factor for these services and their associated inpatient services. Gap analysis can assist in the planning and costing of community mental health services.
An Intensive Community Team in Aged Persons Mental Health
Authors: George Kuruvilla , Giri Shraevani
Published: February 2011

Objective: The aim of this paper was to describe an intensive community team (ICT) in aged persons’ mental health. The rationale for setting up the team, the principles, service activity and findings from the evaluation of the service are discussed.

Conclusions: The program was found to provide substantial support and benefit for patients. ICT does not replace the need for acute inpatient beds but it does provide an opportunity for some patients, who otherwise would have been admitted, to be managed in their homes. It also has the potential of reducing the length of stay for a number of patients.
Consumer Strategies for Coping With Antipsychotic Medication Side Effects
Authors: Meehan Tom , Stedman Terry , Wallace Jane
Published: February 2011

Objective: This study was designed to investigate the strategies employed by consumers to manage the common side effects associated with antipsychotic medication use.

Method: Focus group discussions and individual interviews involving 238 consumers, 25 carers and 16 mental health staff were employed to identify key side effects and a range of consumer coping strategies for managing these adverse effects.

Results: Nine side effects were selected from a total pool of 32 proposed in the group discussions. Strategies that were perceived by the participants to be useful in coping with the selected side effects were then identified.

Conclusions: While the strategies proposed for each side effect differed, common themes included the maintenance of a balanced lifestyle, healthy eating and sleeping routines, and fostering a positive outlook on life. Understanding the strategies employed by consumers to deal with the adverse effects of their medications may help clinicians to engage more effectively with consumers in the discussion and management of side effects.
Pathology in the Medical Curriculum in the United Kingdom
Authors: Reid William A.
Published: February 2011

In the United Kingdom, the medical students of yesteryear undertook a detailed pathology course, often with its own major examinations. This contributed to the increasing overload of factual information that was common in medical curricula. Following General Medical Council reports on medical education, pathology is now more fully integrated into clinical work and into problem-based learning, albeit with greatly reduced contact time with pathologists. Teaching methods have shifted from didactic presentations, such as lectures, to more varied methods, with emphasis on self-access and interactivity. Technological advances have brought well-illustrated textbooks, computer-assisted learning programs, Web resources, and electronic communication. There has been a decline in the role of museum specimens, microscopy, and, partly following a worldwide trend and partly following adverse media publicity, the traditional autopsy. Assessment methods have evolved, with integration of pathology into wider examinations. The greater drive toward increasing funding through the Research Assessment Exercise has had an adverse effect on teaching throughout universities. Despite these setbacks, the importance of pathology as a clinical discipline will ensure its continued role in medical education.
Virtual Microscopy in a Veterinary Curriculum
Authors: Sims Michael H. , Mendis-Handagama Chamindrani , Moore Robert N.
Published: February 2011

Teaching faculty in the University of Tennessee College of Veterinary Medicine assist students in their professional education by providing a new way of viewing microscopic slides digitally. Faculty who teach classes in which glass slides are used participate in a program called Virtual Microscopy. Glass slides are digitized using a state-of-the-art integrated system, and a personal computer functions as the “microscope.” Additionally, distribution of the interactive images is enhanced because they are available to students online.

The digital slide offers equivalent quality and resolution to the original glass slide viewed on a microscope and has several additional advantages over microscopes. Students can choose to examine the entire slide at any of several objectives; they are able to access the slides (called WebSlides) from the college's server, using either Internet Explorer or a special browser developed by Bacus Laboratories, Inc.,a called the WebSlide browser, which lets the student simultaneously view a low-objective image and one or two high-objective images of the same slide. The student can “move the slide” by clicking and dragging the image to a new location. Easy archiving, annotation of images, and Web conferencing are additional features of the system.
Evolution of a Course in Veterinary Clinical Pathology: The Application of Case-Based Writing Assignments to Focus on Skill Development and Facilitation of Learning
Authors: Sharkey Leslie , Overmann Jed , Flash Pamela
Published: February 2011

Rationale for study – To encourage application and critical thinking, case-based writing assignments and grading rubrics were developed for use in a second-year core clinical pathology course. Objectives were to describe how this teaching technique was adapted to a large-class setting and how student perceptions of the learning experience guided modifications of this teaching technique over two presentations of the course and plans for a third presentation. Our goal was to enhance learning by encouraging application of course material to clinical situations and thereby improve students’ ability to organize and communicate information. Furthermore, we evaluated the influence of instructor feedback on the learning process.

Methods – With assistance from the University of Minnesota Center for Writing, assignments and grading rubrics were developed. Students completed course evaluation surveys designed to elicit feedback on the impact of the assignments.

Results – Increased learner confidence was reflected in larger self-reported increases in understanding of the material and ability to apply information and in increased feelings of preparedness for class and examinations. A large majority of students advocated the use of such assignments in the course in future years, and modifications to make grading and evaluation of assignments more efficient are underway.

Conclusions – Investment of faculty and student time in case-based writing assignments in the veterinary clinical pathology curriculum appears to increase student engagement with material and learner confidence. Future studies should address the impact of this type of assignment more specifically on clinical reasoning and communication skills and on long-term retention of material.
Teaching Medical Pathology in the Twenty-First Century: Virtual Microscopy Applications
Authors: Dee Fred R. , Meyerholz David K.
Published: February 2011

Virtual microscopy (VM) has been implemented and evaluated in the histology and general and systemic pathology courses at the University of Iowa Carver College of Medicine. Advantages of VM over traditional microscopy include accessibility and efficiency of learning and the ability to integrate VM with computer-assisted interactive learning. Advantages of using VM as opposed to digital photomicrographs include the ability to pan and zoom, explore the slide, and make independent observations. Although VM is used in a case-based format for teaching histopathology to medical students at the University of Iowa, VM may also be effectively implemented in other medical-student teaching models, including integrated and problem-based learning curricula and the classical pathology laboratory. Additional Iowa venues and courses using VM teaching include pathology of human disease for bioscience graduate students, cytology education, a comparative pathology research resource, and histology and histopathology for veterinary medicine. This article reviews the history and evolution of VM in medical pathology and its implementation at Iowa.
Residency Training Programs in Veterinary Clinical Pathology: A Comparison of Experiences at Two Institutions
Authors: Raskin Rose E.
Published: February 2011

Two institutions with different residency training formats in clinical pathology are compared with respect to application procedures, learning and teaching opportunities, learning resources, research training, publication requirements, and assessment methods of the program and trainees. The University of Florida and Purdue University programs are both based on an emphasis in morphologic recognition and interpretation of disease processes as well as training in basic science and applied research principles. The progress of trainees through each program is carefully monitored to meet individual needs as well as to meet the training requirements to allow candidates to sit for the certifying examination in clinical pathology. Periodic mock board exams are a critical tool to assess trainee progress and learning. The differences in format focus on coursework and publication requirements as well as on program assessment tools. While one program provides training in the form of 75% clinical diagnostic service, the other uses a mixture of 50% coursework and 50% clinical diagnostic training. Despite the contrast between a pure residency training program and one combining residency training with an MS degree, both institutions provide a solid program structure, ample learning resources, and adequate faculty mentorship to produce a high pass rate of board-certified specialists, the major focus for both programs. Numbers of post-training employment positions for both institutions are similar for those selecting faculty positions at veterinary schools. During the period studied, however, the combined residency and MS graduate program at Purdue University produced more graduates employed in pharmaceutical and biotechnology companies, while the residency program at the University of Florida produced more graduates employed by diagnostic laboratories.
The ECVP/ESVP Summer School in Veterinary Pathology: High-Standard, Structured Training for Young Veterinary Pathologists
Authors: Kipar Anja , Aleksandersen Mona , Benazzi Cinzia , Hodge Thomas , Sukura Antti , Wyers Monique ,   (the Education Committee of the ECVP/ESVP)
Published: February 2011

This article describes the ECVP/ESVP Summer School in Veterinary Pathology, a new annual two-week European training facility established by the European College of Veterinary Pathologists (ECVP) in collaboration with the European Society of Veterinary Pathology (ESVP). The aim of the Summer Schools is to provide Europe-wide, harmonized, top-standard theoretical and practical post-graduate training for veterinarians specializing in veterinary pathology. In particular, it aims to support trainees in veterinary pathology in their individual preparation for the ECVP certifying examination. Ultimately, it aims to provide young pathologists with the skills and knowledge necessary to participate in international, high-quality research and the tools for applying international standards to their own research and for independent study for the ECVP certifying examination, even if they do not work in comparable academic environments and do not have the same level of local support and training. The ECVP/ESVP Summer Schools take place in European countries, with local organization from a university department of veterinary pathology. Each event comprises modules provided by internationally recognized specialists in their specific fields of expertise on different organ systems, diseases of specific species, specific techniques, and specific topics relevant to pathology, forming a cycle of four events to cover all major topics. Every two years a mock exam is organized as a tool to monitor individual progress in preparing for the ECVP certifying examination.