bluuebunny/crossref_metadata_2025 huggingface dataset:
RNAase-III enzyme Dicer maintains signaling pathways for differentiation and survival in mouse cortical neural stem cells
Authors: Kawase-Koga Yoko , Low Roger , Otaegi Gaizka , Pollock Andrew , Deng Haiteng , Eisenhaber Frank , Maurer-Stroh Sebastian , Sun Tao
Published: January 2010

An important function of the RNAase-III enzyme Dicer is to process microRNA precursors into ~22-nucleotide non-coding small RNAs. But little is known about the role of Dicer in mammalian brain formation and neural stem cell (NSC) development. Here we show that Dicer plays a crucial role in controlling mouse cortical NSC development. We found that Dicer function is essential for expanding cortical neural progenitors and NSCs. We have identified a population of Dicer-deficient NSCs that can self-renew, and that display normal karyotype and heterochromatin protein expression levels but show enlarged nuclei. Dicer-deficient NSCs display abnormal differentiation and undergo cell death when mitogens are withdrawn. Dicer deletion affects the levels of many proteins, as revealed by a mass spectrometry proteomic approach. We have found that an increase of anti-survival and/or pro-apoptosis proteins and a decrease of pro-survival and/or anti-apoptosis proteins contribute to the cell death of Dicer-deficient NSCs, implying a general role for Dicer in protecting cells from apoptosis. Our results demonstrate important functions for Dicer in regulating NSC development by maintaining proper signaling pathways related to cell survival and differentiation.
Degradation of an intramitochondrial protein by the cytosolic proteasome
Authors: Azzu Vian , Brand Martin D.
Published: January 2010

Mitochondrial uncoupling protein 2 (UCP2) is implicated in a wide range of pathophysiological processes, including immunity and diabetes mellitus, but its rapid degradation remains uncharacterized. Using pharmacological proteasome inhibitors, immunoprecipitation, dominant negative ubiqbiquitiuitin mutants, cellular fractionation and siRNA techniques, we demonstrate the involvement of the ubiquitin-proteasome system in the rapid degradation of UCP2. Importantly, we resolve the issue of whether intramitochondrial proteins can be degraded by the cytosolic proteasome by reconstituting a cell-free system that shows rapid proteasome-inhibitor-sensitive UCP2 degradation in isolated, energised mitochondria presented with an ATP regenerating system, ubiquitin and 26S proteasome fractions. These observations provide the first demonstration that a mitochondrial inner membrane protein is degraded by the cytosolic ubiquitin-proteasome system.
Cholesterol reduction impairs exocytosis of synaptic vesicles
Authors: Linetti Anna , Fratangeli Alessandra , Taverna Elena , Valnegri Pamela , Francolini Maura , Cappello Valentina , Matteoli Michela , Passafaro Maria , Rosa Patrizia
Published: January 2010

Cholesterol and sphingolipids are abundant in neuronal membranes, where they help the organisation of the membrane microdomains involved in major roles such as axonal and dendritic growth, and synapse and spine stability. The aim of this study was to analyse their roles in presynaptic physiology. We first confirmed the presence of proteins of the exocytic machinery (SNARES and Cav2.1 channels) in the lipid microdomains of cultured neurons, and then incubated the neurons with fumonisin B (an inhibitor of sphingolipid synthesis), or with mevastatin or zaragozic acid (two compounds that affect the synthesis of cholesterol by inhibiting HMG-CoA reductase or squalene synthase). The results demonstrate that fumonisin B and zaragozic acid efficiently decrease sphingolipid and cholesterol levels without greatly affecting the viability of neurons or the expression of synaptic proteins. Electron microscopy showed that the morphology and number of synaptic vesicles in the presynaptic boutons of cholesterol-depleted neurons were similar to those observed in control neurons. Zaragozic acid (but not fumonisin B) treatment impaired synaptic vesicle uptake of the lipophilic dye FM1-43 and an antibody directed against the luminal epitope of synaptotagmin-1, effects that depended on the reduction in cholesterol because they were reversed by cholesterol reloading. The time-lapse confocal imaging of neurons transfected with ecliptic SynaptopHluorin showed that cholesterol depletion affects the post-depolarisation increase in fluorescence intensity. Taken together, these findings show that reduced cholesterol levels impair synaptic vesicle exocytosis in cultured neurons.
Inelastic response of structures due to large impact and blast loadings
Authors: Jones N
Published: January 2010

This article provides a broad overview of the contributions that relatively simple methods of analysis can make to the design of structural systems for the protection of the public and the security of industrial plant against extreme dynamic loading events which involve explosive blast pressures or impact loadings from fragments and projectiles. It is possible, by careful design, to absorb the external dynamic energies through large inelastic deformations of the structural members and specially designed energy-absorbing and cladding systems. Experimental studies are important because the large impact loadings produce inelastic strains and highly non-linear structural responses. The dynamic properties of ductile materials, including inelastic failure, the impact response of pipelines, and the scaling laws required for predicting the behaviour of full-scale prototypes from experiments on small-scale structures, are also discussed. Some phenomena are emphasized that are important for numerical finite element schemes as well as theoretical methods of analysis.
An improved fuzzy programming model with an L—R fuzzy number for filter management strategies in fluid power systems under uncertainty
Authors: Nie S L , Xiong Z B , Li Y P , Huang G H , Hu Z
Published: January 2010

A fuzzy non-linear programming model is developed for the assessment of filter allocation and replacement strategies in fluid power systems (FPSs) under uncertainty. It can not only handle uncertainties expressed as L—R fuzzy numbers, but also enhance the system robustness by transforming the fuzzy inequalities into inclusive constraints. In modelling formulation, theory of contamination wear is introduced to reflect the interactions between system performance and system contamination level. The developed method has been applied to the planning of filter allocation and replacement for an FPS with a bypass filtration system, and a piecewise linearization approach is proposed for solving model non-linearities. Three different contaminant ingression rates are examined based on a number of filter-installation scenarios. The generated solutions can be used for providing guidance to decision makers to identify better contamination control plans for achieving a minimized system cost and system-failure risk.
A two-system, single-analysis, fluid—structure interaction technique for modelling abdominal aortic aneurysms
Authors: Kelly S C , O'Rourke M J
Published: January 2010

This work reports on the implementation and validation of a two-system, single-analysis, fluid—structure interaction (FSI) technique that uses the finite volume (FV) method for performing simulations on abdominal aortic aneurysm (AAA) geometries. This FSI technique, which was implemented in OpenFOAM, included fluid and solid mesh motion and incorporated a non-linear material model to represent AAA tissue. Fully implicit coupling was implemented, ensuring that both the fluid and solid domains reached convergence within each time step. The fluid and solid parts of the FSI code were validated independently through comparison with experimental data, before performing a complete FSI simulation on an idealized AAA geometry. Results from the FSI simulation showed that a vortex formed at the proximal end of the aneurysm during systolic acceleration, and moved towards the distal end of the aneurysm during diastole. Wall shear stress (WSS) values were found to peak at both the proximal and distal ends of the aneurysm and remain low along the centre of the aneurysm. The maximum von Mises stress in the aneurysm wall was found to be 408 kPa, and this occurred at the proximal end of the aneurysm, while the maximum displacement of 2.31 mm occurred in the centre of the aneurysm. These results were found to be consistent with results from other FSI studies in the literature.
COPD Management in Primary Care: An Observational, Community Pharmacy–Based Study
Authors: Mehuys Els , Boussery Koen , Adriaens Els , Bortel Luc Van , Bolle Leen De , Tongelen Inge Van , Remon Jean-Paul , Brusselle Guy
Published: January 2010

Background:

Chronic obstructive pulmonary disease (COPD) is a prevalent disease that is frequently treated in primary care. However, data regarding the primary care management of COPD are scarce. Such observational data are necessary to detect problem areas and to develop targeted interventions for improvement of COPD management.

Objective:

To provide a detailed description of (1) drug therapy, (2) drug adherence, (3) inhalation technique, and (4) health status of patients with COPD recruited via community pharmacies.

Methods:

A cross-sectional, observational study was conducted in 93 pharmacies in Belgium. Participants (N = 555) completed a questionnaire collecting information on personal characteristics, smoking history, influenza vaccination, COPD medication, and adverse effects. Adherence to COPD maintenance medication was analyzed 1 year retrospectively through prescription refill rates. Inhalation technique was scored using a checklist. Health status was evaluated with the St. George's Respiratory Questionnaire, the Clinical COPD Questionnaire, and the Modified Medical Research Council dyspnea scale.

Results:

The mean age of the patients was 68.6 years; 73.7% were men and 37.2% were current smokers. The influenza vaccination status was significantly lower in patients aged less than 65 years (65.7%) than in patients aged 65 years or more (86.2%) (p < 0.001). Fixed combinations of inhaled corticosteroids and long-acting β2-agonists were the most frequently used COPD medications (75.4%). About 48% of patients were underadherent (<80% adherence), 47% were adherent (80–120% adherence) and 5% were overadherent (>120% adherence). Predictors for underadherence were age and number of drugs. Twenty-one percent of patients made major inhalation technique errors with rescue medication; these were all errors in handling pressurized metered-dose inhalers (pMDIs).

Conclusions:

This observational study on COPD management in primary care highlights 4 main aspects that could be improved: (1) drug adherence, (2) inhalation technique with pMDIs, (3) influenza vaccination in COPD patients younger than 65 years, and (4) smoking cessation.
Glutamatergic Inputs Contribute to Phasic Activity in Vasopressin Neurons
Authors: Israel Jean-Marc , Poulain Dominique A. , Oliet Stéphane H. R.
Published: January 2010

Many neurons in the CNS display rhythmic patterns of activity to optimize excitation–secretion coupling. However, the mechanisms of rhythmogenesis are only partially understood. Magnocellular vasopressin (VP) neurons in the hypothalamus display a phasic activity that consists of alternative bursts of action potentials and silent periods. Previous observations from acute slices of adult hypothalamus suggested that VP cell rhythmicity depends on intrinsic membrane properties. However, such activityin vivois nonregenerative. Here, we studied the mechanisms of VP neuron rhythmicity in organotypic slice cultures that, unlike acute slices, preserve functional synaptic connections. Comparative analysis of phasic firing of VP neuronsin vivo, in acute slices, and in the cultures revealed that, in the latter, the activity was closely related to that observedin vivo. It was synaptically driven, essentially from glutamatergic inputs, and did not rely on intrinsic membrane properties. The glutamatergic synaptic activity was sensitive to osmotic challenges and κ-opioid receptor activation, physiological stimuli known to affect phasic activity. Together, our data thus strongly suggest that phasic activity in magnocellular VP neurons is controlled by glutamatergic synaptic inputs rather than by intrinsic properties.
The Scale of Functional Specialization within Human Prefrontal Cortex: Figure 1.
Authors: Gilbert Sam J. , Henson Richard N. A. , Simons Jon S.
Published: January 2010

At what scale is it possible to observe consistent functional specialization within human prefrontal cortex (PFC), reproducible from one individual to the next? Some studies suggest gross functional divisions between large regions of PFC, but it is not known whether PFC exhibits specialization at the fine-grained scale known to differentiate posterior cortical functions. We used fMRI to confirm a three-way segregation of function between three regions of medial anterior PFC, each centered on coordinates within 15 mm of the other two. Naive participants performed three tasks based on earlier studies, and we investigated activity at regions defined by previous results. In each task, signal was significantly greater at the predicted region than the other two, just millimeters away. These results indicate reproducible functional specialization within PFC, at a much finer scale than previously demonstrated. Furthermore, these findings suggest that divergent results from previous studies may reflect the recruitment of functionally distinct regions and that “reverse inference” should be undertaken with caution.
Acute Dynamin Inhibition Dissects Synaptic Vesicle Recycling Pathways That Drive Spontaneous and Evoked Neurotransmission
Authors: Chung ChiHye , Barylko Barbara , Leitz Jeremy , Liu Xinran , Kavalali Ege T.
Published: January 2010

Synapses maintain synchronous, asynchronous, and spontaneous forms of neurotransmission that are distinguished by their Ca2+dependence and time course. Despite recent advances in our understanding of the mechanisms that underlie these three forms of release, it remains unclear whether they originate from the same vesicle population or arise from distinct vesicle pools with diverse propensities for release. Here, we used a reversible inhibitor of dynamin, dynasore, to dissect the vesicle pool dynamics underlying the three forms of neurotransmitter release in hippocampal GABAergic inhibitory synapses. In dynasore, evoked synchronous release and asynchronous neurotransmission detected after activity showed marked and unrecoverable depression within seconds. In contrast, spontaneous release remained intact after intense stimulation in dynasore or during prolonged (∼1 h) application of dynasore at rest, suggesting that separate recycling pathways maintain evoked and spontaneous synaptic vesicle trafficking. In addition, simultaneous imaging of spectrally separable styryl dyes revealed that, in a given synapse, vesicles that recycle spontaneously and in response to activity do not mix. These findings suggest that evoked synchronous and asynchronous release originate from the same vesicle pool that recycles rapidly in a dynamin-dependent manner, whereas a distinct vesicle pool sustains spontaneous release independent of dynamin activation. This result lends additional support to the notion that synapses harbor distinct vesicle populations with divergent release properties that maintain independent forms of neurotransmission.
Neuronal Synchronization in Human Posterior Parietal Cortex during Reach Planning
Authors: Van Der Werf Jurrian , Jensen Ole , Fries Pascal , Medendorp W. Pieter
Published: January 2010

Although single-unit studies in monkeys have identified effector-related regions in the posterior parietal cortex (PPC) during saccade and reach planning, the degree of effector specificity of corresponding human regions, as established by recordings of the blood oxygen level-dependent signal, is still under debate. Here, we addressed this issue from a different perspective, by studying the neuronal synchronization of the human PPC during both reach and saccade planning. Using magnetoencephalography (MEG), we recorded ongoing brain activity while subjects performed randomly alternating trials of memory-guided reaches or saccades. Additionally, subjects performed a dissociation task requiring them to plan both a memory-guided saccade and reach to locations in opposing visual hemifields. We examined changes in spectral power of the MEG signal during a 1.5 s memory period in relation to target location (left/right) and effector type (eye/hand). The results show direction-selective synchronization in the 70–90 Hz gamma frequency band, originating from the medial aspect of the PPC, when planning a reaching movement. In contrast, activity in a more central portion of the PPC was synchronized in a lower gamma band (50–60 Hz) when planning the direction of a saccade. Both observations were corroborated in the dissociation task. In the lower frequency bands, we observed sustained alpha-band (8–12 Hz) desynchronization in occipitoparietal regions, but in an effector-unspecific manner. These results suggest that distinct modules in the posterior parietal cortex encode movement goals of different effectors by selective gamma-band activity, compatible with the functional organization of monkey PPC.
Identification of the Zebrafish Ventral Habenula As a Homolog of the Mammalian Lateral Habenula
Authors: Amo Ryunosuke , Aizawa Hidenori , Takahoko Mikako , Kobayashi Megumi , Takahashi Rieko , Aoki Tazu , Okamoto Hitoshi
Published: January 2010

The mammalian habenula consists of the medial and lateral habenulae. Recent behavioral and electrophysiological studies suggested that the lateral habenula plays a pivotal role in controlling motor and cognitive behaviors by influencing the activity of dopaminergic and serotonergic neurons. Despite the functional significance, manipulating neural activity in this pathway remains difficult because of the absence of a genetically accessible animal model such as zebrafish. To address the level of lateral habenula conservation in zebrafish, we applied the tract-tracing technique to GFP (green fluorescent protein)-expressing transgenic zebrafish to identify habenular neurons that project to the raphe nuclei, a major target of the mammalian lateral habenula. Axonal tracing in live and fixed fish showed projection of zebrafish ventral habenula axons to the ventral part of the median raphe, but not to the interpeduncular nucleus where the dorsal habenula projected. The ventral habenula expressedprotocadherin 10a, a specific marker of the rat lateral habenula, whereas the dorsal habenula showed no such expression. Gene expression analyses revealed that the ventromedially positioned ventral habenula in the adult originated from the region of primordium lateral to the dorsal habenula during development. This suggested that zebrafish habenulae emerge during development with mediolateral orientation similar to that of the mammalian medial and lateral habenulae. These findings indicated that the lateral habenular pathways are evolutionarily conserved pathways and might control adaptive behaviors in vertebrates through the regulation of monoaminergic activities.
Expression of β-Amyloid Induced Age-Dependent Presynaptic and Axonal Changes in Drosophila
Authors: Zhao Xiao-Liang , Wang Wen-An , Tan Jiang-Xiu , Huang Jian-Kang , Zhang Xiao , Zhang Bao-Zhu , Wang Yu-Hang , YangCheng Han-Yu , Zhu Hong-Lian , Sun Xiao-Jiang , Huang Fu-De
Published: January 2010

Alzheimer's disease (AD) is attributable to synapse dysfunction and loss, but the nature and progression of the presynaptic structural and functional changes in AD are essentially unknown. We expressed wild-type or arctic form of β amyloid1-42(Aβ) in a small group of neurons in the adult fly and performed extensive time course analysis of the function and structure of both axon and presynaptic terminals at the identified single-neuron level. Aβ accumulated intracellularly and induced a range of age-dependent changes, including depletion of presynaptic mitochondria, slowdown of bi-directional transports of axonal mitochondria, decreased synaptic vesicles, increased large vacuoles, and elevated synaptic fatigue. These structural and functional synaptic changes correlated with age-dependent deficit in motor behavior. All these alterations were accelerated in flies expressing the arctic form of Aβ. The depletion of presynaptic mitochondria was the earliest detected phenotype and was not caused by the change in axonal transport of mitochondria. Moreover, axonal mitochondria exhibited a dramatic reduction in number but a significant increase in size in aged Aβ-expressing flies, indicating a global depletion of mitochondria in the neuron and an impairment of mitochondria fission. These results suggest that Aβ accumulation depletes presynaptic and axonal mitochondria, leading to other presynaptic deficits.
The Timing and Location of Glial Cell Line-Derived Neurotrophic Factor Expression Determine Enteric Nervous System Structure and Function
Authors: Wang Hongtao , Hughes Inna , Planer William , Parsadanian Alexander , Grider John R. , Vohra Bhupinder P. S. , Keller-Peck Cynthia , Heuckeroth Robert O.
Published: January 2010

Ret signaling is critical for formation of the enteric nervous system (ENS) because Ret activation promotes ENS precursor survival, proliferation, and migration and provides trophic support for mature enteric neurons. Although these roles are well established, we now provide evidence that increasing levels of the Ret ligand glial cell line-derived neurotrophic factor (GDNF) in mice causes alterations in ENS structure and function that are critically dependent on the time and location of increased GDNF availability. This is demonstrated using two different strains of transgenic mice and by injecting newborn mice with GDNF. Furthermore, because different subclasses of ENS precursors withdraw from the cell cycle at different times during development, increases in GDNF at specific times alter the ratio of neuronal subclasses in the mature ENS. In addition, we confirm that esophageal neurons are GDNF responsive and demonstrate that the location of GDNF production influences neuronal process projection for NADPH diaphorase-expressing, but not acetylcholinesterase-, choline acetyltransferase-, or tryptophan hydroxylase-expressing, small bowel myenteric neurons. We further demonstrate that changes in GDNF availability influence intestinal functionin vitroandin vivo. Thus, changes in GDNF expression can create a wide variety of alterations in ENS structure and function and may in part contribute to human motility disorders.
Developmental Regulation of Spontaneous Activity in the Mammalian Cochlea
Authors: Tritsch Nicolas X. , Bergles Dwight E.
Published: January 2010

Neurons in the developing auditory system fire bursts of action potentials before the onset of hearing. This spontaneous activity promotes the survival and maturation of auditory neurons and the refinement of synaptic connections in auditory nuclei; however, the mechanisms responsible for initiating this activity remain uncertain. Previous studies indicate that inner supporting cells (ISCs) in the developing cochlea periodically release ATP, which depolarizes inner hair cells (IHCs), leading to bursts of action potentials in postsynaptic spiral ganglion neurons (SGNs). To determine when purinergic signaling appears in the developing cochlea and whether it is responsible for initiating auditory neuron activity throughout the prehearing period, we examined spontaneous activity from ISCs, IHCs, and SGNs in cochleae acutely isolated from rats during the first three postnatal weeks. We found that ATP was released from ISCs within the cochlea from birth until the onset of hearing, which led to periodic inward currents, Ca2+transients, and morphological changes in these supporting cells. This spontaneous release of ATP also depolarized IHCs and triggered bursts of action potentials in SGNs for most of the postnatal prehearing period, beginning a few days after birth as IHCs became responsive to ATP, until the onset of hearing when ATP was no longer released from ISCs. When IHCs were not subject to purinergic excitation, SGNs exhibited little or no activity. These results suggest that supporting cells in the cochlea provide the primary excitatory stimulus responsible for initiating bursts of action potentials in auditory nerve fibers before the onset of hearing.
Enhanced Efficacy without Further Cleft Closure: Reevaluating Twist as a Source of Agonist Efficacy in AMPA Receptors
Authors: Birdsey-Benson Amanda , Gill Avinash , Henderson Leslie P. , Madden Dean R.
Published: January 2010

AMPA receptors (AMPARs) are tetrameric ligand-gated ion channels that couple the energy of glutamate binding to the opening of a transmembrane channel. Crystallographic and electrophysiological analysis of AMPARs has suggested a coupling between (1) cleft closure in the bilobate ligand-binding domain (LBD), (2) the resulting separation of transmembrane helix attachment points across subunit dimers, and (3) agonist efficacy. In general, more efficacious agonists induce greater degrees of cleft closure and transmembrane separation than partial agonists. Several apparent violations of the cleft-closure/efficacy paradigm have emerged, although in all cases, intradimer separation remains as the driving force for channel opening. Here, we examine the structural basis of partial agonism in GluA4 AMPARs. We find that the L651V substitution enhances the relative efficacy of kainate without increasing either LBD cleft closure or transmembrane separation. Instead, the conformational change relative to the wild-type:kainate complex involves a twisting motion with the efficacy contribution opposite from that expected based on previous analyses. As a result, channel opening may involve transmembrane rearrangements with a significant rotational component. Furthermore, a two-dimensional analysis of agonist-induced GluA2 LBD motions suggests that efficacy is not a linearly varying function of lobe 2 displacement vectors, but is rather determined by specific conformational requirements of the transmembrane domains.
When Desire Collides with Reason: Functional Interactions between Anteroventral Prefrontal Cortex and Nucleus Accumbens Underlie the Human Ability to Resist Impulsive Desires
Authors: Diekhof Esther K. , Gruber Oliver
Published: January 2010

Human decisions are guided by “desire” or “reason,” which control actions oriented toward either proximal or long-term goals. Here we used functional magnetic resonance imaging to assess how the human brain mediates the balance between proximal reward desiring and long-term goals, when actions promoting a superordinate goal preclude exploitation of an immediately available reward option. Consistent with the view that the reward system interacts with prefrontal circuits during action control, we found that behavior favoring the long-term goal, but counteracting immediate reward desiring, relied on a negative functional interaction of anteroventral prefrontal cortex (avPFC) with nucleus accumbens (Nacc) and ventral tegmental area. The degree of functional interaction between avPFC and Nacc further predicted behavioral success during pursuit of the distal goal, when confronted with a proximal reward option, and scaled with interindividual differences in trait impulsivity. These findings reveal how the human brain accomplishes voluntary action control guided by “reason,” suggesting that inhibitory avPFC influences Nacc activity during actions requiring a restraint of immediate “desires.”
Laminar Restriction of Retinal Ganglion Cell Dendrites and Axons: Subtype-Specific Developmental Patterns Revealed with Transgenic Markers
Authors: Kim In-Jung , Zhang Yifeng , Meister Markus , Sanes Joshua R.
Published: January 2010

Retinal ganglion cells (RGCs), which transfer information from the eye to the brain, are heterogeneous in structure and function, but developmental studies have generally treated them as a single group. Here, we investigate the development of RGC axonal and dendritic arbors using four mouse transgenic lines in which nonoverlapping subsets of RGCs are indelibly labeled with a fluorescent protein. Each subset has a distinct functional signature, size, and morphology. Dendrites of each subset are restricted to specific sublaminae within the inner plexiform layer in adulthood, but acquire their restriction in different ways: one subset has lamina-restricted dendrites from an early postnatal stage, a second remodels an initially diffuse pattern, and two others develop stepwise. Axons of each subset arborize in discrete laminar zones within the lateral geniculate nucleus or superior colliculus, demonstrating previously unrecognized subdivisions of retinorecipient layers. As is the case for dendrites, lamina-restricted axonal projections of RGC subsets develop in different ways. For example, while axons of two RGC subsets arborize in definite zones of the superior colliculus from an early postnatal stage, axons of another subset initially occupy a deep layer, then translocate to a narrow subpial zone. Together, these results show that RGC subsets use a variety of strategies to construct lamina-restricted dendritic and axonal arbors. Taking account of these subtype-specific features will facilitate identification of the molecules and cells that regulate arbor formation.
Readiness Discharge for Spontaneous Initiation of Walking in Crayfish
Authors: Kagaya Katsushi , Takahata Masakazu
Published: January 2010

Animals initiate behavior not only reflexively but also spontaneously in the absence of external stimuli. In vertebrates, electrophysiological data on the neuronal activity associated with the self-initiated voluntary behavior have accumulated extensively. In invertebrates, however, little is known about the neuronal basis of the spontaneous initiation of behavior. We investigated the spike activity of brain neurons at the time of spontaneous initiation of walking in the crayfishProcambarus clarkiiand found neuronal signals indicative of readiness or preparatory activities in the vertebrate brain that precede the onset of voluntary actions. Those readiness discharge neurons became active >1 s before the initiation of walking regardless of stepping direction. They remained inactive at the onset of mechanical stimulus-evoked walking in which other descending units were recruited. These results suggest that the parallel descending mechanisms from the brain separately subserve the spontaneous and stimulus-evoked walking. Electrical stimulation of these different classes of neurons caused different types of walking. In addition, we found other descending units that represented different aspects of walking, including those units that showed a sustained activity increase throughout the walking bout depending on its stepping direction, as well as one veto unit for canceling out the output effect of the readiness discharge and three termination units for stopping the walking behavior. These findings suggest that the descending activities are modularized in parallel for spontaneous initiation, continuation, and termination of walking, constituting a sequentially hierarchical control.
Difference in Binocularity and Ocular Dominance Plasticity between GABAergic and Excitatory Cortical Neurons
Authors: Kameyama Katsuro , Sohya Kazuhiro , Ebina Teppei , Fukuda Atsuo , Yanagawa Yuchio , Tsumoto Tadaharu
Published: January 2010

Neuronal circuits in the cerebral cortex consist mainly of glutamatergic/excitatory and GABAergic/inhibitory neurons. In the visual cortex, the binocular responsiveness of neurons is modified by monocular visual deprivation during the critical period of postnatal development. Although GABAergic neurons are considered to play a key role in the expression of the critical period, it is not known whether their binocular responsiveness and ocular dominance plasticity are different from those of excitatory neurons. Recently, the end of the critical period was found to be not strict so that cortical neurons in the adult still have some ocular dominance plasticity. It is not known, however, which type of neurons or both maintain such plasticity in adulthood. To address these issues, we appliedin vivotwo-photon functional Ca2+imaging to transgenic mice whose GABAergic neurons express a yellow fluorescent protein called Venus. We found that GABAergic neurons are more binocular than excitatory neurons in the normal visual cortex, and both types of neurons show the same degree of modifiability to monocular visual deprivation during the critical period, but the modifiability of GABAergic neurons is stronger than that of excitatory neurons after the end of the critical period.
Rapid, Reversible Modulation of Blood–Brain BarrierP-Glycoprotein Transport Activity by Vascular Endothelial Growth Factor
Authors: Hawkins Brian T. , Sykes Destiny B. , Miller David S.
Published: January 2010

Increased brain expression of vascular endothelial growth factor (VEGF) is associated with neurological disease, brain injury, and blood–brain barrier (BBB) dysfunction. However, the specific effect of VEGF on the efflux transporter P-glycoprotein, a critical component of the BBB, is not known. Using isolated rat brain capillaries andin siturat brain perfusion, we determined the effect of VEGF exposure on P-glycoprotein activityin vitroandin vivo. In isolated capillaries, VEGF acutely and reversibly decreased P-glycoprotein transport activity without decreasing transporter protein expression or opening tight junctions. This effect was blocked by inhibitors of the VEGF receptor flk-1 and Src kinase, but not by inhibitors of phosphatidylinositol-3-kinase or protein kinase C. VEGF also increased Tyr-14 phosphorylation of caveolin-1, and this was blocked by the Src inhibitor PP2. Pharmacological activation of Src kinase activity mimicked the effects of VEGF on P-glycoprotein activity and Tyr-14 phosphorylation of caveolin-1.In vivo, intracerebroventricular injection of VEGF increased brain distribution of P-glycoprotein substrates morphine and verapamil, but not the tight junction marker, sucrose; this effect was blocked by PP2. These findings indicate that VEGF decreases P-glycoprotein activity via activation of flk-1 and Src, and suggest Src-mediated phosphorylation of caveolin-1 may play a role in downregulation of P-glycoprotein activity. These findings also imply that P-glycoprotein activity is acutely diminished in pathological conditions associated with increased brain VEGF expression and that BBB VEGF/Src signaling could be targeted to acutely modulate P-glycoprotein activity and thus improve brain drug delivery.
A Neural Basis for Motor Primitives in the Spinal Cord
Authors: Hart Corey B. , Giszter Simon F.
Published: January 2010

Motor primitives and modularity may be important in biological movement control. However, their neural basis is not understood. To investigate this, we recorded 302 neurons, making multielectrode recordings in the spinal cord gray of spinalized frogs, at 400, 800, and 1200 μm depth, at the L2/L3 segment border. Simultaneous muscle activity recordings were used with independent components analysis to infer premotor drive patterns. Neurons were divided into groups based on motor pattern modulation and sensory responses, depth recorded, and behavior. The 187 motor pattern modulated neurons recorded comprised 14 cutaneous neurons and 28 proprioceptive neurons at 400 μm in the dorsal horn, 131 intermediate zone interneurons from ∼800 μm depth without sensory responses, and 14 motoneuron-like neurons at ∼1200 μm. We examined all such neurons during spinal behaviors. Mutual information measures showed that cutaneous neurons and intermediate zone neurons were related better to premotor drives than to individual muscle activity. In contrast, proprioceptive-related neurons and ventral horn neurons divided evenly. For 46 of the intermediate zone interneurons, we found significant postspike facilitation effects on muscle responses using spike-triggered averages representing short-latency postspike facilitations to multiple motor pools. Furthermore, these postspike facilitations matched significantly in both their patterns and strengths with the weighting parameters of individual primitives extracted statistically, although both were initially obtained without reference to one another. Our data show that sets of dedicated interneurons may organize individual spinal primitives. These may be a key to understanding motor development, motor learning, recovery after CNS injury, and evolution of motor behaviors.
Four novel RET germline variants in exons 8 and 11 display an oncogenic potential in vitro
Authors: Muzza Marina , Cordella Daniela , Bombled Johny , Bressac-de Paillerets Brigitte , Guizzardi Fabiana , Francis Zelia , Beck-Peccoz Paolo , Schlumberger Martin , Persani Luca , Fugazzola Laura
Published: January 2010

Context

Most germline-activating mutations of theRETproto-oncogene associated with inherited medullary thyroid cancer (MTC) are localized in exons 10, 11 and 13–15. Four novelRETvariants, located in the extracellular domain (p.A510V, p.E511K and p.C531R) coded by exon 8 and in the intracellular juxtamembrane region (p.K666N) coded by exon 11, were identified on the leukocyte DNA from apparently sporadic cases.

Methods

Plasmids carrying Ret9-wild-type (Ret9-WT), Ret9-C634R and all Ret9 variants were transfected, and the phosphorylation levels of RET and ERK were evaluated by western blot analyses. The transforming potentials were assessed by the focus formation assay.

Results

The p.A510V, p.E511K and p.C531R variants were found to generate RET and ERK phosphorylation levels and to have a transforming activity higher than that of Ret9-WT variant, but lower than that of Ret9-C634R variant. Differently, the p.K666N variant, located immediately downstream of the transmembrane domain, and involving a conserved residue, displayed high kinase and transforming activities. Computational analysis predicted non-conservative alterations in the mutant proteins consistent with putative modifications of the receptor conformation.

Conclusions

The molecular analyses revealed an oncogenic potential for all the novel germlineRETvariants. Therefore, the prevalence of exon 8 genomic variations with an oncogenic potential may be higher than previously thought, and the analysis of this exon should be considered after the exclusion of mutations in the classical hotspots. In addition, on the basis of these functional data, it is advisable to extend the genetic screening to all the first-degree relatives of the MTC patients, and to perform a strict follow-up of familial carriers.
Order-to-disorder transformation in δ-phase Sc4Zr3O12 induced by light ion irradiation
Authors: Zhang Jian , Wang Yongqiang , Tang Ming , Won Jonghan , Valdez James A. , Sickafus Kurt E.
Published: January 2010

Polycrystalline δ-phase Sc4Zr3O12 was irradiated with 200 keV Ne+ ions at cryogenic temperature to fluences ranging from 2 × 1018 to 1 × 1021 Ne/m2. Irradiation-induced structural evolution was examined by using grazing incidence x-ray diffraction and cross-sectional transmission electron microscopy. An order-to-disorder (O-D) crystal structure transformation (from an ordered δ-phase to a disordered, fluorite phase) was observed to initiate by a fluence of 2 × 1018 Ne/m2, corresponding to a peak ballistic damage dose of ∼0.075 displacements per atom. This displacement damage dose is much lower than the O-D transformation dose threshold found in previous heavy ion irradiation experiments on δ-Sc4Zr3O12 [J.A. Valdez et al., Nucl. Instrum. Methods B250, 148 (2006); K.E. Sickafus et al., Nat. Mater.6, 217 (2007)]. In this study, we contrast the O-D transformation efficiency of the light Ne ions used in these experiments, to the heavy (Kr) ions used previously, and interpret the differences in terms of enhanced damage efficiency for light ions (greater fraction of surviving defects per defect produced). To better quantify this surviving defect phenomenon, we also present new, additional ion irradiation results on δ-Sc4Zr3O12, obtained from 300 keV Kr2+ and 100 keV He+ ion irradiation experiments.
Effect of sequential desilication and dealumination on catalytic performance of ZSM-5 catalyst for pyridine and 3-picoline synthesis
Authors: Jin Fang , Cui Yugang , Rui Zebao , Li Yongdan
Published: January 2010

A sequential procedure of alkaline treatment followed by SiCl4 or hydrothermal treatment has been investigated to obtain a tailored ZSM-5 catalyst for the synthesis of pyridine bases. The major function of alkaline treatment is desilication; however, it is accompanied by the extraction of framework aluminum, which formed the extra-framework alumina and amorphous alumina by realumination. Moreover, a large number of intracrystalline meso- and macropores and silanol groups are created. The desilication and realumination cause the ratio of Lewis acid sites to Brönsted acid sites (L/B) to increase. The subsequent SiCl4 or hydrothermal dealumination increases both L/B ratio and acid strength. The introduced hierarchical pores and changed acid strength distribution by the alkaline treatment improve the stability of the catalysts; the generated stronger acid sites by dealumination benefits the yields of pyridine bases; and the increased L/B by the sequential treatment promotes the selectivity of pyridine over 3-picoline.
Improving tensile and fatigue properties of Sn–58Bi/Cu solder joints through alloying substrate
Authors: Zhang QingKe , Zou HeFei , Zhang Zhe-Feng
Published: January 2010

To eliminate the Bi segregation and interfacial embrittlement of the SnBi/Cu joints, we deliberately added some Ag or Zn elements into the Cu substrate. Then, the reliability of the SnBi/Cu–X (X = Ag or Zn) solder joints was evaluated by investigating their interfacial reactions, tensile property, and fatigue life compared with those of the SnBi/Cu and SnAg/Cu joints. The experimental results demonstrate that even after aging for a long time, the addition of the Ag or Zn elements into the Cu substrate can effectively eliminate the interfacial Bi embrittlement of the SnBi/Cu–X joints under tensile or fatigue loadings. Compared with the conventional SnAg/Cu joints, the SnBi/Cu–X joints exhibit higher adhesive strength and comparable fatigue resistance. Finally, the fatigue and fracture mechanisms of the SnBi/Cu–X solder joints were discussed qualitatively. The current findings may pave the new way for the Sn–Bi solder widely used in the electronic interconnection in the future.
Hydrogen in tungsten: Absorption, diffusion, vacancy trapping, and decohesion
Authors: Johnson Donald F. , Carter Emily A.
Published: January 2010

Understanding the interaction between atomic hydrogen and solid tungsten is important for the development of fusion reactors in which proposed tungsten walls would be bombarded with high energy particles including hydrogen isotopes. Here, we report results from periodic density-functional theory calculations for three crucial aspects of this interaction: surface-to-subsurface diffusion of H into W, trapping of H at vacancies, and H-enhanced decohesion, with a view to assess the likely extent of hydrogen isotope incorporation into tungsten reactor walls. We find energy barriers of (at least) 2.08 eV and 1.77 eV for H uptake (inward diffusion) into W(001) and W(110) surfaces, respectively, along with very small barriers for the reverse process (outward diffusion). Although H dissolution in defect-free bulk W is predicted to be endothermic, vacancies in bulk W are predicted to exothermically trap multiple H atoms. Furthermore, adsorbed hydrogen is predicted to greatly stabilize W surfaces such that decohesion (fracture) may result from high local H concentrations.
Organic-ligand-assisted hydrothermal synthesis of ultrafine and hydrophobic ZnO nanoparticles
Authors: Mousavand Tahereh , Ohara Satoshi , Naka Takashi , Umetsu Mitsuo , Takami Seiichi , Adschiri Tadafumi
Published: January 2010

In this study, we report the synthesis of uniform and narrowly size-distributed ZnO nanoparticles with sizes of approximately 3 nm; the nanoparticles were prepared by means of organic-ligand-assisted hydrothermal conditions with various organic modifiers. The results obtained herein revealed that among the various functional groups tested (alcohols, aldehydes, carboxylic acids, and amines), only hexanol effectively controlled the nucleation and crystal growth of spherical ZnO nanoparticles. The use of hexanol also caused the surface of the ZnO particles to change from hydrophilic to hydrophobic, which would enhance the dispersion of these particles in polymer matrices, paints, cosmetics, and other organic application media.
Revelation of solid solubility limit Fe/Ni = 1/12 in corrosion resistant Cu-Ni alloys and relevant cluster model
Authors: Zhang Jie , Wang Qing , Wang Yingmin , Li Chunyan , Wen Lishi , Dong Chuang
Published: January 2010

Minor Fe additions are necessary to enhance the corrosion resistance of commercial Cu-Ni alloys. The present paper aims at optimizing the Fe content in three alloy series Cu90(Ni,Fe)10, Cu80(Ni,Fe)20, and Cu70(Ni,Fe)30 (at.%) from the viewpoint of their corrosion performance in a 3.5% NaCl solution. An Fe/Ni = 1/12 solid solubility limit line was revealed in the Cu-Ni-Fe phase diagram. Three Fe/Ni = 1/12 alloys, Cu90Ni9.23Fe0.77 (at.%) = Cu-8.6Ni-0.7Fe (wt.%), Cu80Ni18.46Fe1.54 = Cu-17.3Ni-1.4Fe, and Cu70Ni27.7Fe2.3 = Cu-26.2Ni-2.1Fe, show the best corrosion performances in their respective alloy series. The Fe/Ni = 1/12 solubility limit is explained by assuming isolated Fe-centered FeNi12 cuboctahedral clusters embedded in a Cu matrix. The three Fe/Ni = 1/12 alloys can be respectively described by cluster formulas [Fe1Ni12]Cu117, [Fe1Ni12]Cu52, and [Fe1Ni12]Cu30.3. The Fe/Ni = 1/12 rule may serve an important guideline in the industrial Cu-Ni alloy selection because above this limit, easy precipitation would negate the corrosion properties of the Cu-Ni-based alloys.
Conventional Vickers and true instrumented indentation hardness determined by instrumented indentation tests
Authors: Kang Seung-Kyun , Kim Ju-Young , Park Chan-Pyoung , Kim Hyun-Uk , Kwon Dongil
Published: January 2010

We evaluate Vickers hardness and true instrumented indentation test (IIT) hardness of 24 metals over a wide range of mechanical properties using just IIT parameters by taking into account the real contact morphology beneath the Vickers indenter. Correlating the conventional Vickers hardness, indentation contact morphology, and IIT parameters for the 24 metals reveals relationships between contact depths and apparent material properties. We report the conventional Vickers and true IIT hardnesses measured only from IIT contact depths; these agree well with directly measured hardnesses within ±6% for Vickers hardness and ±10% for true IIT hardness.
Influence of MgO codoping on Er concentration in congruent LiNbO3 crystal: Mg threshold concentration effect
Authors: Zhang De-Long , Zhang Li-Zhu , Xu Chao , Sun Liang , Xu Yu-Heng , Pun Edwin Yue-Bun
Published: January 2010

Congruent Er:Mg:LiNbO3 crystals were grown by the Czochralski method from the melts containing fixed 0.5 mol% Er2O3 while varied MgO content ranged from 0.0 to 8.0 mol%. The Mg and Er contents in the crystals were determined by neutron activation analysis. In the presence of Er codopant, the Mg threshold concentration with respect to optical damage is determined from the measured OH absorption spectra. The results show that the Er codopant has less effect on both the Mg threshold concentration and Mg segregation coefficient, which is within 1.13–1.23 as the Mg concentration is below the threshold while within 0.88–0.98 when above the threshold, consistent with the only MgO doping case. On the other hand, the practical Er concentration in the crystal is closely related to the Mg content and shows definite Mg threshold effect. Below the threshold, the Er concentration decreases linearly with the increased Mg concentration in the crystal; above the threshold, the decrease is more remarkable and follows another linear function. The Mg concentration effect on the Er segregation coefficient is discussed from the viewpoint of the Mg doping effect on the solubility of Er ions in the crystal.