bluuebunny/crossref_metadata_2025 huggingface dataset:
Análise do Comprometimento Organizacional e sua Natureza em Relação aos Funcionários Públicos Municipais
Authors: Roman Sidnei , Stefano Silvio Roberto , Andrade Sandra Mara de , Zampier Marcia Aparecida
Published: May 2013

O objetivo desse artigo é identificar o tipo de comprometimento organizacional dos colaboradores da prefeitura municipal da cidade de Pitanga no Estado do Paraná, tomando como foco o modelo multidimensional do comprometimento descrito por Meyer e Allen (1990, 1991 e 1993) o qual analisa três fatores do comprometimento organizacional: afetivo, normativo e instrumental. Foi realizada uma pesquisa exploratória, sendo apresentado um diagnostico comparativo entre os fatores do comprometimento. O universo composto por 50 colaboradores efetivos foi pesquisado em sua totalidade. Os resultados apontaram  o comprometimento na base afetiva como o mais expressivo entre os fatores analisados com uma média de 3,83 numa escala de 5 pontos, seguido do comprometimento normativo  (3,45),  ficando o comprometimento na base instrumental com 3,25. As médias obtidas tendem a indicar um nível satisfatório do comprometimento devido a forma de análise proposta para esta escala, observando-se assim um  nível adequado de comprometimento organizacional na instituição pesquisada.
O Consumidor de Café Expresso em Minas Gerais: Diferenças, Hábitos e Preferências
Authors: Sampaio Danilo de Oliveira , Coelho Alexandre Bragança , Gosling Marlusa , Fagundes André Francisco Alcântara , Sousa Caissa Veloso e
Published: May 2013

Considerando-se a relevância de se compreender os impactos de agregar valor a uma commodity, além da importância do café para a economia brasileira, esse artigo objetiva entender os motivos que influenciam a escolha dos consumidores de café expresso em importantes centros urbanos de Minas Gerais. Para tanto, empreendeu-se uma comparação de quatro regiões mineiras com a capital do estado. As variáveis escolhidas para o estudo foram: gênero, faixa etária, renda, ocupação, escolaridade, prática esportiva e hábito de consumo. A metodologia foi descritiva exploratória, com análise quantitativa por meio do modelo Logit, sendo este capaz de interpretar variáveis de resposta qualitativa. Os consumidores foram entrevistados em varejos de rua e em shoppings centers. Os resultados sugerem que os principais determinantes do consumo de café expresso em Minas Gerais são: (a) as preferências ou hábitos; (b) localização geográfica; (c) renda; (d) gênero; e (e) escolaridade – com destaque para as duas primeiras.
A Dinâmica das Ações Cotidianas Articuladas pelos Coordenadores e Diretores na Implementação da Estratégia.
Authors: Schwingel Andressa Thaís , Generoso Paula Guadanhim , Lavarda Rosalia Aldraci Barbosa
Published: May 2013

O objetivo do estudo é analisar como ocorre o processo de implementação da estratégia, considerando como os estrategistas desenvolvem as ações estratégicas em uma Instituição de Ensino Superior (IES) pública. Foi adotada metodologia qualitativa por meio do estudo de caso. A seleção do caso foi de forma intencional e por conveniência (organização complexa). As técnicas de coleta de dados foram entrevistas, análise documental e observação direta. A análise dos dados foi por meio de análise narrativa e técnica pattern matching. A dinâmica das ações cotidianas e seus reflexos evidenciam como o coordenador e diretores fazem a estratégia acontecer caracterizando o resultado estratégico, alcançando os objetivos e metas organizacionais. Os resultados evidenciaram a implementação da estratégia por meio da participação ativa dos praticantes, decorrente do envolvimento de diversos atores que possuem comportamentos, características e visões diferentes no processo analisado.
Increased Cell-Intrinsic Excitability Induces Synaptic Changes in New Neurons in the Adult Dentate Gyrus That Require Npas4
Authors: Sim Shuyin , Antolin Salome , Lin Chia-Wei , Lin Yingxi , Lois Carlos
Published: May 2013

Electrical activity regulates the manner in which neurons mature and form connections to each other. However, it remains unclear whether increased single-cell activity is sufficient to alter the development of synaptic connectivity of that neuron or whether a global increase in circuit activity is necessary. To address this question, we genetically increased neuronal excitability ofin vivoindividual adult-born neurons in the mouse dentate gyrus via expression of a voltage-gated bacterial sodium channel. We observed that increasing the excitability of new neurons in an otherwise unperturbed circuit leads to changes in both their input and axonal synapses. Furthermore, the activity-dependent transcription factor Npas4 is necessary for the changes in the input synapses of these neurons, but it is not involved in changes to their axonal synapses. Our results reveal that an increase in cell-intrinsic activity during maturation is sufficient to alter the synaptic connectivity of a neuron with the hippocampal circuit and that Npas4 is required for activity-dependent changes in input synapses.
Presynaptic NMDA Receptor Mechanisms for Enhancing Spontaneous Neurotransmitter Release
Authors: Kunz Portia A. , Roberts Adam C. , Philpot Benjamin D.
Published: May 2013

NMDA receptors (NMDARs) are required for experience-driven plasticity during formative periods of brain development and are critical for neurotransmission throughout postnatal life. Most NMDAR functions have been ascribed to postsynaptic sites of action, but there is now an appreciation that presynaptic NMDARs (preNMDARs) can modulate neurotransmitter release in many brain regions, including the neocortex. Despite these advances, the cellular mechanisms by which preNMDARs can affect neurotransmitter release are largely unknown. Here we interrogated preNMDAR functions pharmacologically to determine how these receptors promote spontaneous neurotransmitter release in mouse primary visual cortex. Our results provide three new insights into the mechanisms by which preNMDARs can function. First, preNMDARs can enhance spontaneous neurotransmitter release tonically with minimal extracellular Ca2+or with major sources of intracellular Ca2+blocked. Second, lowering extracellular Na+levels reduces the contribution of preNMDARs to spontaneous transmitter release significantly. Third, preNMDAR enhance transmitter release in part through protein kinase C signaling. These data demonstrate that preNMDARs can act through novel pathways to promote neurotransmitter release in the absence of action potentials.
eGFP Expression underUCHL1Promoter Genetically Labels Corticospinal Motor Neurons and a Subpopulation of Degeneration-Resistant Spinal Motor Neurons in an ALS Mouse Model
Authors: Yasvoina Marina V. , Genç Barış , Jara Javier H. , Sheets Patrick L. , Quinlan Katharina A. , Milosevic Ana , Shepherd Gordon M.G. , Heckman C. J. , Özdinler P. Hande
Published: May 2013

Understanding mechanisms that lead to selective motor neuron degeneration requires visualization and cellular identification of vulnerable neurons. Here we report generation and characterization ofUCHL1-eGFPandhSOD1G93A-UeGFPmice, novel reporter lines for cortical and spinal motor neurons. Corticospinal motor neurons (CSMN) and a subset of spinal motor neurons (SMN) are genetically labeled inUCHL1-eGFPmice, which express eGFP under theUCHL1promoter. eGFP expression is stable and continues through P800in vivo. Retrograde labeling, molecular marker expression, electrophysiological analysis, and cortical circuit mapping confirmed CSMN identity of eGFP+neurons in the motor cortex. Anatomy, molecular marker expression, and electrophysiological analysis revealed that the eGFP expression is restricted to a subset of small-size SMN that are slow-twitch α and γ motor neurons. Crossbreeding ofUCHL1-eGFPandhSOD1G93Alines generatedhSOD1G93A-UeGFPmice, which displayed the disease phenotype observed in ahSOD1G93Amouse model of ALS. eGFP+SMN showed resistance to degeneration inhSOD1G93A-UeGFPmice, and their slow-twitch α and γ motor neuron identity was confirmed. In contrast, eGFP+neurons in the motor cortex ofhSOD1G93A-UeGFPmice recapitulated previously reported progressive CSMN loss and apical dendrite degeneration. Our findings using these two novel reporter lines revealed accumulation of autophagosomes along the apical dendrites of vulnerable CSMN at P60, early symptomatic stage, suggesting autophagy as a potential intrinsic mechanism for CSMN apical dendrite degeneration.
Independent Control of Presynaptic Inhibition by Reticulospinal and Sensory Inputs at Rest and during Rhythmic Activities in the Cat
Authors: Sirois Jennifer , Frigon Alain , Gossard Jean-Pierre
Published: May 2013

To be functionally relevant during movement, the transmission from primary afferents must be efficiently controlled by presynaptic inhibition. Sensory feedback, central pattern generators, and supraspinal structures can all evoke presynaptic inhibition, but we do not understand how these inputs interact during movement. Here, we investigated the convergence of inputs from the reticular formation and sensory afferents on presynaptic inhibitory pathways and their modulation at rest and during two fictive motor tasks (locomotion and scratch) in decerebrate cats. The amplitude of primary afferent depolarization (PAD), an estimate of presynaptic inhibition, was recorded in individual afferents with intra-axonal recordings and in a mix of afferents in lumbar dorsal rootlets (dorsal root potential [DRP]) with bipolar electrodes. There was no spatial facilitation between inputs from reticulospinal and sensory afferents with DRPs or PADs, indicating an absence of convergence. However, spatial facilitation could be observed by combining two sensory inputs, indicating that convergence was possible. Task-dependent changes in the amplitude of responses were similar for reticulospinal and sensory inputs, increasing during fictive locomotion and decreasing during fictive scratch. During fictive locomotion, DRP and PAD amplitudes evoked by reticulospinal inputs were increased during the flexion phase, whereas sensory-evoked DRPs and PADs showed maximal amplitude in either flexion or extension phases. During fictive scratch, the amplitudes of DRPs and PADs evoked by both sources were maximal in flexion. The absence of spatial facilitation and different phase-dependent modulation patterns during fictive locomotion are consistent with independent presynaptic inhibitory pathways for reticulospinal and sensory inputs.
Primary Hippocampal Neurons, Which Lack Four Crucial Extracellular Matrix Molecules, Display Abnormalities of Synaptic Structure and Function and Severe Deficits in Perineuronal Net Formation
Authors: Geissler Maren , Gottschling Christine , Aguado Ainhara , Rauch Uwe , Wetzel Christian H. , Hatt Hanns , Faissner Andreas
Published: May 2013

The extracellular matrix (ECM) of the brain plays crucial roles during the development, maturation, and regeneration of the CNS. In a subpopulation of neurons, the ECM condenses to superstructures called perineuronal nets (PNNs) that surround synapses. Camillo Golgi described PNNs a century ago, yet their biological functions remain elusive. Here, we studied a mouse mutant that lacks four ECM components highly enriched in the developing brain: the glycoproteins tenascin-C and tenascin-R and the chondroitin sulfate proteoglycans brevican and neurocan. Primary embryonic hippocampal neurons and astrocytes were cultivated using a cell insert system that allows for co-culture of distinct cell populations in the absence of direct membrane contacts. The wild-type and knock-out cells were combined in the four possible permutations. Using this approach, neurons cultivated in the presence of mutant astrocytes displayed a transient increase of synapses after 2 weeks. However, after a period of 3 weeks or longer, synapse formation and stabilization were compromised when either neuron or astrocyte cell populations or both were of mutant origin. The development of PNN structures was observed, but their size was substantially reduced on knock-out neurons. The synaptic activity of both wild-type and knock-out neurons was monitored using whole-cell patch clamping. The salient observation was a reduced frequency of IPSCs and EPSCs, whereas the amplitudes were not modified. Remarkably, the knock-out neuron phenotypes could not be rescued by wild-type astrocytes. We conclude that the elimination of four ECM genes compromises neuronal function.
Refractoriness Enhances Temporal Coding by Auditory Nerve Fibers
Authors: Avissar Michael , Wittig John H. , Saunders James C. , Parsons Thomas D.
Published: May 2013

A universal property of spiking neurons is refractoriness, a transient decrease in discharge probability immediately following an action potential (spike). The refractory period lasts only one to a few milliseconds, but has the potential to affect temporal coding of acoustic stimuli by auditory neurons, which are capable of submillisecond spike-time precision. Here this possibility was investigated systematically by recording spike times from chicken auditory nerve fibersin vivowhile stimulating with repeated pure tones at characteristic frequency. Refractory periods were tightly distributed, with a mean of 1.58 ms. A statistical model was developed to recapitulate each fiber's responses and then used to predict the effect of removing the refractory period on a cell-by-cell basis for two largely independent facets of temporal coding: faithful entrainment of interspike intervals to the stimulus frequency and precise synchronization of spike times to the stimulus phase. The ratio of the refractory period to the stimulus period predicted the impact of refractoriness on entrainment and synchronization. For ratios less than ∼0.9, refractoriness enhanced entrainment and this enhancement was often accompanied by an increase in spike-time precision. At higher ratios, little or no change in entrainment or synchronization was observed. Given the tight distribution of refractory periods, the ability of refractoriness to improve temporal coding is restricted to neurons responding to low-frequency stimuli. Enhanced encoding of low frequencies likely affects sound localization and pitch perception in the auditory system, as well as perception in nonauditory sensory modalities, because all spiking neurons exhibit refractoriness.
Feature-Specific Information Processing Precedes Concerted Activation in Human Visual Cortex
Authors: Ramkumar Pavan , Jas Mainak , Pannasch Sebastian , Hari Riitta , Parkkonen Lauri
Published: May 2013

Current knowledge about the precise timing of visual input to the cortex relies largely on spike timings in monkeys and evoked-response latencies in humans. However, quantifying the activation onset does not unambiguously describe the timing of stimulus-feature-specific information processing. Here, we investigated the information content of the early human visual cortical activity by decoding low-level visual features from single-trial magnetoencephalographic (MEG) responses. MEG was measured from nine healthy subjects as they viewed annular sinusoidal gratings (spanning the visual field from 2 to 10° for a duration of 1 s), characterized by spatial frequency (0.33 cycles/degree or 1.33 cycles/degree) and orientation (45° or 135°); gratings were either static or rotated clockwise or anticlockwise from 0 to 180°. Time-resolved classifiers using a 20 ms moving window exceeded chance level at 51 ms (the later edge of the window) for spatial frequency, 65 ms for orientation, and 98 ms for rotation direction. Decoding accuracies of spatial frequency and orientation peaked at 70 and 90 ms, respectively, coinciding with the peaks of the onset evoked responses. Within-subject time-insensitive pattern classifiers decoded spatial frequency and orientation simultaneously (mean accuracy 64%, chance 25%) and rotation direction (mean 82%, chance 50%). Classifiers trained on data from other subjects decoded the spatial frequency (73%), but not the orientation, nor the rotation direction. Our results indicate that unaveraged brain responses contain decodable information about low-level visual features already at the time of the earliest cortical evoked responses, and that representations of spatial frequency are highly robust across individuals.
Dendritic Translocation Establishes the Winner in Cerebellar Climbing Fiber Synapse Elimination
Authors: Carrillo Jennifer , Nishiyama Naoko , Nishiyama Hiroshi
Published: May 2013

In many regions of the developing mammalian nervous system, functional synaptic circuitry is formed by competitive elimination of early formed redundant synapses. However, how winning synapses emerge through competition remains unclear in the brain largely because of the technical difficulty of directly observing this dynamic cellular processin vivo. Here, we developed a method of two-photon multicolor vital imaging to observe competitive elimination of supernumerary climbing fibers (CFs) in the cerebellum of live mouse pups. At birth, each Purkinje cell (PC) in the cerebellar cortex is innervated by multiple CFs; an activity-dependent regression of supernumerary CFs ultimately yields a single innervation for most PCs by postnatal day 21. As supernumerary CFs are pruned, the terminal field of CFs translocates from the soma to the dendrites of PCs.In vivotime-lapse imaging of CF elimination revealed that (1) CF terminals were highly motile on the soma, but their motility was significantly reduced on dendrites; (2) only one CF could translocate to the dendrites whereas their competitors were restricted to perisomatic regions; and (3) the CF that began dendritic translocation became the winner. Moreover, selective photo-ablation of the winning CF (that undergoes dendritic translocation) reversed the fate of its losing competitor. These results indicate that dendritic translocation is a key cellular event that determines the winner during CF elimination. We propose that CF terminals are selectively stabilized on dendrites, providing irreversible competitive vigor to the first CF to form dendritic synapses.
Potentiation of Inhibitory Synaptic Transmission by Extracellular ATP in Rat Suprachiasmatic Nuclei
Authors: Bhattacharya Anirban , Vavra Vojtech , Svobodova Irena , Bendova Zdena , Vereb Gyorgy , Zemkova Hana
Published: May 2013

The hypothalamic suprachiasmatic nuclei (SCN), the circadian master clock in mammals, releases ATP in a rhythm, but the role of extracellular ATP in the SCN is still unknown. In this study, we examined the expression and function of ATP-gated P2X receptors (P2XRs) in the SCN neurons of slices isolated from the brain of 16- to 20-day-old rats. Quantitative RT-PCR showed that the SCN contains mRNA for P2X 1–7 receptors and several G-protein-coupled P2Y receptors. Among the P2XR subunits, theP2X2>P2X7>P2X4mRNAs were the most abundant. Whole-cell patch-clamp recordings from SCN neurons revealed that extracellular ATP application increased the frequency of spontaneous GABAergic IPSCs without changes in their amplitudes. The effect of ATP appears to be mediated by presynaptic P2X2Rs because ATPγS and 2MeS-ATP mimics, while the P2XR antagonist PPADS blocks, the observed enhancement of the frequency of GABA currents. There were significant differences between two SCN regions in that the effect of ATP was higher in the ventrolateral subdivision, which is densely innervated from outside the SCN. Little evidence was found for the presence of P2XR channels in somata of SCN neurons as P2X2R immunoreactivity colocalized with synapsin and ATP-induced current was observed in only 7% of cells. In fura-2 AM-loaded slices, BzATP as well as ADP stimulated intracellular Ca2+increase, indicating that the SCN cells express functional P2X7 and P2Y receptors. Our data suggest that ATP activates presynaptic P2X2Rs to regulate inhibitory synaptic transmission within the SCN and that this effect varies between regions.
Glucocorticoid Signaling in Myeloid Cells Worsens Acute CNS Injury and Inflammation
Authors: Sorrells Shawn F. , Caso Javier R. , Munhoz Carolina D. , Hu Caroline K. , Tran Kevin V. , Miguel Zurine D. , Chien Bonnie Y. , Sapolsky Robert M.
Published: May 2013

Glucocorticoid stress hormones (GCs) are well known for being anti-inflammatory, but some reports suggest that GCs can also augment aspects of inflammation during acute brain injury. Because the GC receptor (GR) is ubiquitously expressed throughout the brain, it is difficult to know which cell types might mediate these unusual “proinflammatory” GC actions. We examined this with cell type-specific deletion or overexpression of GR in mice experiencing seizure or ischemia. Counter to their classical anti-inflammatory actions, GR signaling in myeloid cells increased Iba-1 and CD68 staining as well as nuclear p65 levels in the injured tissue. GCs also reduced levels of occludin, claudin 5, and caveolin 1, proteins central to blood–brain-barrier integrity; these effects required GR in endothelial cells. Finally, GCs compromised neuron survival, an effect mediated by GR in myeloid and endothelial cells to a greater extent than by neuronal GR.
Postural Reorganization Induced by Torso Cutaneous Covibration
Authors: Lee Beom-Chan , Martin Bernard J. , Ho Allison , Sienko Kathleen H.
Published: May 2013

Cutaneous information from joints has been attributed proprioceptive properties similar to those of muscle spindles. This study aimed to assess whether vibration-induced changes in torso cutaneous information contribute to whole-body postural reorganization in humans. Ten healthy young adults stood in normal and Romberg stances with six vibrating actuators positioned on the torso in contact with the skin over the left and right external oblique, internal oblique, and erector spinae muscle locations at the L4/L5 vertebrae level. Vibrations around the torso were randomly applied at two locations simultaneously (covibration) or at all locations simultaneously. Kinematic analysis of the body segments indicated that covibration applied to the skin over the internal oblique muscles induced shifts of both the head and torso in the anterior direction (torso flexion) while the hips shifted in the posterior direction (ankle plantar flexion). Conversely, covibration applied to the skin over the erector spinae muscle locations produced opposite effects. However, covibration applied to the skin over the left internal oblique and left erector spinae, the right internal oblique and right erector spinae, or at all locations simultaneously did not induce any significant postural changes. In addition, the center of pressure position as measured by the force plate was unaffected by all covibration conditions tested. These results were independent of stance and suggest an integrated and coordinated reorganization of posture in response to vibration-induced changes in cutaneous information. In addition, combinations of vibrotactile stimuli over multiple locations exhibit directional summation properties in contrast to the individual responses we observed in our previous work.
Fractalkine Signaling in Microglia Contributes to Ectopic Orofacial Pain following Trapezius Muscle Inflammation
Authors: Kiyomoto Masaaki , Shinoda Masamichi , Okada-Ogawa Akiko , Noma Noboru , Shibuta Kazuo , Tsuboi Yoshiyuki , Sessle Barry J. , Imamura Yoshiki , Iwata Koichi
Published: May 2013

Fractalkine (FKN) signaling is involved in mechanical allodynia in the facial skin following trapezius muscle inflammation. Complete Freund's adjuvant (CFA) injection into the trapezius muscle produced mechanical allodynia in the ipsilateral facial skin that was not associated with facial skin inflammation and resulted in FKN but not FKN receptor (CX3CR1) expression, and microglial activation was enhanced in trigeminal spinal subnucleus caudalis (Vc) and upper cervical spinal cord (C1–C2). Intra-cisterna magna anti-CX3CR1 or anti-interleukin (IL)-1β neutralizing antibody administration decreased the enhanced excitability of Vc and C1–C2 neurons in CFA-injected rats, whereas intra-cisterna magna FKN administration induced microglial activation and mechanical allodynia in the facial skin. IL-1β expression and p38 mitogen-activated protein kinase phosphorylation were enhanced in activated microglia after CFA injection. The excitability of neurons whose receptive fields was located in the facial skin was significantly enhanced in CFA-injected rats, and the number of cells expressing phosphorylated extracellular signal-regulated kinase (pERK) following noxious mechanical stimulation of the facial skin was significantly increased in Vc and C1–C2. We also observed mechanical allodynia of the trapezius muscle as well as microglial activation and increased pERK expression in C2–C6 after noxious stimulation of the trapezius muscle in facial skin-inflamed rats. These findings suggest that FKN expression was enhanced in Vc and C1–C2 or C2–C6 following trapezius muscle or facial skin inflammation, microglia are activated via FKN signaling, IL-1β is released from the activated microglia, and the excitability of neurons in Vc and C1–C2 or C2-C6 is enhanced, resulting in the ectopic mechanical allodynia.
Reciprocal Homosynaptic and Heterosynaptic Long-Term Plasticity of Corticogeniculate Projection Neurons in Layer VI of the Mouse Visual Cortex
Authors: Arami Masoumeh Kourosh , Sohya Kazuhiro , Sarihi Abdolrahman , Jiang Bin , Yanagawa Yuchio , Tsumoto Tadaharu
Published: May 2013

Most neurons in layer VI of the visual cortex project to the dorsal lateral geniculate nucleus (dLGN). These corticogeniculate projection neurons (CG cells) receive top-down synaptic inputs from upper layers (ULs) and bottom-up inputs from the underlying white matter (WM). Use-dependent plasticity of these synapses in layer VI of the cortex has received less attention than in other layers. In the present study, we used a retrograde tracer injected into dLGN to identify CG cells, and, by analyzing EPSPs evoked by electrical stimulation of the UL or WM site, examined whether these synapses show long-term synaptic plasticity. Theta-burst stimulation induced long-term potentiation (LTP) of activated synapses (hom-LTP) and long-term depression (LTD) of nonactivated synapses (het-LTD) in either pathway. The paired-pulse stimulation protocol and the analysis of coefficient variation of EPSPs suggested postsynaptic induction of these changes except UL-induced het-LTD, which may be presynaptic in origin. Intracellular injection of a Ca2+-chelator suggested an involvement of postsynaptic Ca2+rise in all types of long-term plasticity. Pharmacological analysis indicated that NMDA receptors and type-5 metabotropic glutamate receptors are involved in WM-induced and UL-induced plasticity, respectively. Analysis with inhibitors and/or in transgenic mice suggested an involvement of cannabinoid type 1 receptors and calcineurin in UL-induced and WM-induced het-LTD, respectively. These results suggest that hom-LTP and het-LTD may play a role in switching the top-down or bottom-up regulation of CG cell function and/or in maintaining stability of synaptic transmission efficacy through different molecular mechanisms.
cAMP-Mediated Stabilization of Fusion Pores in Cultured Rat Pituitary Lactotrophs
Authors: Calejo Ana Isabel , Jorgačevski Jernej , Kucka Marek , Kreft Marko , Gonçalves Paula P. , Stojilkovic Stanko S. , Zorec Robert
Published: May 2013

Regulated exocytosis mediates the release of hormones and transmitters. The last step of this process is represented by the merger between the vesicle and the plasma membranes, and the formation of a fusion pore. Once formed, the initially stable and narrow fusion pore may reversibly widen (transient exocytosis) or fully open (full-fusion exocytosis). Exocytosis is typically triggered by an elevation in cytosolic calcium activity. However, other second messengers, such as cAMP, have been reported to modulate secretion. The way in which cAMP influences the transitions between different fusion pore states remains unclear. Here, hormone release studies show that prolactin release from isolated rat lactotrophs stimulated by forskolin, an activator of adenylyl cyclases, and by membrane-permeable cAMP analog (dbcAMP), exhibit a biphasic concentration dependency. Although at lower concentrations (2–10 μmforskolin and 2.5–5 mmdbcAMP) these agents stimulate prolactin release, an inhibition is measured at higher concentrations (50 μmforskolin and 10–15 mmdbcAMP). By using high-resolution capacitance (Cm) measurements, we recorded discrete increases in Cm, which represent elementary exocytic events. An elevation of cAMP leaves the frequency of full-fusion events unchanged while increasing the frequency of transient events. These exhibited a wider fusion pore as measured by increased fusion pore conductance and a prolonged fusion pore dwell time. The probability of observing rhythmic reopening of transient fusion pores was elevated by dbcAMP. In conclusion, cAMP-mediated stabilization of wide fusion pores prevents vesicles from proceeding to the full-fusion stage of exocytosis, which hinders vesicle content discharge at high cAMP concentrations.
Phox2b-Expressing Retrotrapezoid Neurons Are Intrinsically Responsive to H+and CO2
Authors: Wang Sheng , Shi Yingtang , Shu Shaofang , Guyenet Patrice G. , Bayliss Douglas A.
Published: May 2013

Central respiratory chemoreceptors sense changes in CO2/H+and initiate the adjustments to ventilation required to preserve brain and tissue pH. The cellular nature of the sensors (neurons and/or glia) and their CNS location are not conclusively established but the glutamatergic, Phox2b-expressing neurons located in the retrotrapezoid nucleus (RTN) are strong candidates. However, a direct demonstration that RTN neurons are intrinsically sensitive to CO2/H+, required for designation as a chemosensor, has been lacking. To address this, we tested the pH sensitivity of RTN neurons that were acutely dissociated from two lines of Phox2b-GFP BAC transgenic mice. All GFP-labeled cells assayed by reverse transcriptase-PCR (n= 40) were Phox2b+, VGlut2+, TH−, and ChAT−, the neurochemical phenotype previously defined for chemosensitive RTN neuronsin vivo. We found that most dissociated RTN neurons from both lines of mice were CO2/H+-sensitive (∼79%), with discharge increasing during acidification and decreasing during alkalization. The pH-sensitive cells could be grouped into two populations characterized by similar pH sensitivity but different basal firing rates, as previously observed in recordings from GFP-labeled RTN neurons in slice preparations. In conclusion, these data indicate that RTN neurons are inherently pH-sensitive, as expected for a respiratory chemoreceptor.
Maternal protein restriction leads to enhanced hepatic gluconeogenic gene expression in adult male rat offspring due to impaired expression of the liver X receptor
Authors: Vo Thin Xuan , Revesz Andrew , Sohi Gurjeev , Ma Noelle , Hardy Daniel B
Published: May 2013

Epidemiological studies demonstrate that the link between impaired fetal development and glucose intolerance in later life is exacerbated by postnatal catch-up growth. Maternal protein restriction (MPR) during pregnancy and lactation in the rat has been previously demonstrated to lead to impaired glucose tolerance in adulthood, however the effects of protein restoration during weaning on glucose homeostasis are largely unknown. Recentin vitrostudies have identified that the liver X receptor α (LXRα) maintains glucose homeostasis by inhibiting critical genes involved in gluconeogenesis includingG6pase(G6pc),11β-Hsd1(Hsd11b1) andPepck(Pck1). Therefore, we hypothesized that MPR with postnatal catch-up growth would impair LXRαin vivo, which in turn would lead to augmented gluconeogenic LXRα-target gene expression and glucose intolerance. To examine this hypothesis, pregnant Wistar rats were fed a control (20%) protein diet (C) or a low (8%) protein diet during pregnancy and switched to a control diet at birth (LP). At 4 months, the LP offspring had impaired glucose tolerance. In addition, LP offspring had decreased LXRα expression, while hepatic expression of 11β-HSD1 and G6Pase was significantly higher. This was concomitant with decreased binding of LXRα to the putative LXRE on11β-Hsd1andG6pase. Finally, we demonstrated that the acetylation of histone H3 (K9,14) surrounding the transcriptional start site of hepaticLxrα(Nr1h3) was decreased in LP offspring, suggesting MPR-induced epigenetic silencing of theLxrαpromoter. In summary, our study demonstrates for the first time the important role of LXRα in mediating enhanced hepatic gluconeogenic gene expression and consequent glucose intolerance in adult MPR offspring.
Fine-tuning evolution: germ-line epigenetics and inheritance
Authors: Stringer Jessica M , Barrand Sanna , Western Patrick
Published: May 2013

In mice, epiblast cells found both the germ-line and somatic lineages in the developing embryo. These epiblast cells carry epigenetic information from both parents that is required for development and cell function in the fetus and during post-natal life. However, germ cells must establish an epigenetic program that supports totipotency and the configuration of parent-specific epigenetic states in the gametes. To achieve this, the epigenetic information inherited by the primordial germ cells at specification is erased and new epigenetic states are established during development of the male and female germ-lines. Errors in this process can lead to transmission of epimutations through the germ-line, which have the potential to affect development and disease in the parent's progeny. This review discusses epigenetic reprogramming in the germ-line and the transmission of epigenetic information to the following generation.
The subtle intracapsular survival of the fittest: maternal investment, sibling conflict, or environmental effects?
Authors: Smith Kathryn E. , Thatje Sven
Published: May 2013

Developmental resource partitioning and the consequent offspring size variations are of fundamental importance for marine invertebrates, in both an ecological and evolutionary context. Typically, differences are attributed to maternal investment and the environmental factors determining this; additional variables, such as environmental factors affecting development, are rarely discussed. During intracapsular development, for example, sibling conflict has the potential to affect resource partitioning. Here, we investigate encapsulated development in the marine gastropod Buccinum undatum. We examine the effects of maternal investment and temperature on intracapsular resource partitioning in this species. Reproductive output was positively influenced by maternal investment, but additionally, temperature and sibling conflict significantly affected offspring size, number, and quality during development. Increased temperature led to reduced offspring number, and a combination of high sibling competition and asynchronous early development resulted in a common occurrence of “empty” embryos, which received no nutrition at all. The proportion of empty embryos increased with both temperature and capsule size. Additionally, a novel example of a risk in sibling conflict was observed; embryos cannibalized by others during early development ingested nurse eggs from inside the consumer, killing it in a “Trojan horse” scenario. Our results highlight the complexity surrounding offspring fitness. Encapsulation should be considered as significant in determining maternal output. Considering predicted increases in ocean temperatures, this may impact offspring quality and consequently species distribution and abundance.
Periodontal bacterial invasion and infection: contribution to atherosclerotic pathology
Authors: Reyes Leticia , Herrera David , Kozarov Emil , Roldá Silvia , Progulske‐Fox Ann
Published: May 2013

Objective: The objective of this review was to perform a systematic evaluation of the literature reporting current scientific evidence for periodontal bacteria as contributors to atherosclerosis.

Methods: Literature from epidemiological, clinical and experimental studies concerning periodontal bacteria and atherosclerosis were reviewed. Gathered data were categorized into seven “proofs” of evidence that periodontal bacteria: 1) disseminate from the oral cavity and reach systemic vascular tissues; 2) can be found in the affected tissues; 3) live within the affected site; 4) invade affected cell types in vitro; 5) induce atherosclerosis in animal models of disease; 6) non‐invasive mutants of periodontal bacteria cause significantly reduced pathology in vitro and in vivo; and 7) periodontal isolates from human atheromas can cause disease in animal models of infection. Results: Substantial evidence for proofs 1 to 6 was found. However, proof 7 has not yet been fulfilled.

Conclusions: Despite the lack of evidence that periodontal bacteria obtained from human atheromas can cause atherosclerosis in animal models of infection, attainment proofs 1 to 6 provides support that periodontal pathogens can contribute to atherosclerosis.
Adverse pregnancy outcomes (APOs) and periodontal disease: pathogenic mechanisms
Authors: Madianos Phoebus N. , Bobetsis Yiorgos A. , Offenbacher Steven
Published: May 2013

Aim: To evaluate the evidence on potential biological pathways underlying the possible association between periodontal disease (PD) and adverse pregnancy outcomes (APOs). Material & Methods: Human, experimental and in vitro studies were evaluated.

Results: Periodontal pathogens/byproducts may reach the placenta and spread to the foetal circulation and amniotic fluid. Their presence in the foeto‐placental compartment can stimulate a foetal immune/inflammatory response characterized by the production of IgM antibodies against the pathogens and the secretion of elevated levels of inflammatory mediators, which in turn may cause miscarriage or premature birth. Moreover, infection/inflammation may cause placental structural changes leading to pre‐eclampsia and impaired nutrient transport causing low birthweight. Foetal exposure may also result in tissue damage, increasing the risk for perinatal mortality/morbidity. Finally, the elicited systemic inflammatory response may exacerbate local inflammatory responses at the foeto‐placental unit and further increase the risk for APOs.

Conclusions: Further investigation is still necessary to fully translate the findings of basic research into clinical studies and practice. Understanding the systemic virulence potential of the individual's oral microbiome and immune response may be a distinctly different issue from categorizing the nature of the challenge using clinical signs of PD. Therefore, a more personalized targeted therapy could be a more predictive answer to the current “one‐size‐fits‐all” interventions.
Periodontitis and atherosclerotic cardiovascular disease: consensus report of the Joint EFP/AAPWorkshop on Periodontitis and Systemic Diseases
Authors: Tonetti Maurizio S. , Van Dyke Thomas E. ,   on behalf of working group 1 of the joint EFP/AAP workshop
Published: May 2013

Background: This consensus report is concerned with the association between periodontitis and atherosclerotic cardiovascular disease (ACVD). Periodontitis is a chronic multifactorial inflammatory disease caused by microorganisms and characterized by progressive destruction of the tooth supporting apparatus leading to tooth loss; as such, it is a major public health issue.

Aims: This report examined biological plausibility, epidemiology and early results from intervention trials.

Plausibility: Periodontitis leads to entry of bacteria in the blood stream. The bacteria activate the host inflammatory response by multiple mechanisms. The host immune response favors atheroma formation, maturation and exacerbation. Epidemiology: In longitudinal studies assessing incident cardiovascular events, statistically significant excess risk for ACVD was reported in individuals with periodontitis. This was independent of established cardiovascular risk factors. The amount of the adjusted excess risk varies by type of cardiovascular outcome and across populations by age and gender. Given the high prevalence of periodontitis, even low to moderate excess risk is important from a public health perspective.

Intervention: There is moderate evidence that periodontal treatment: (i) reduces systemic inflammation as evidenced by reduction in C‐reactive protein (CRP) and improvement of both clinical and surrogate measures of endothelial function; but (ii) there is no effect on lipid profiles – supporting specificity. Limited evidence shows improvements in coagulation, biomarkers of endothelial cell activation, arterial blood pressure and subclinical atherosclerosis after periodontal therapy. The available evidence is consistent and speaks for a contributory role of periodontitis to ACVD. There are no periodontal intervention studies on primary ACVD prevention and there is only one feasibility study on secondary ACVD prevention.

Conclusions: It was concluded that: (i) there is consistent and strong epidemiologic evidence that periodontitis imparts increased risk for future cardiovascular disease; and (ii) while in vitro, animal and clinical studies do support the interaction and biological mechanism, intervention trials to date are not adequate to draw further conclusions. Well‐designed intervention trials on the impact of periodontal treatment on prevention of ACVD hard clinical outcomes are needed.
Periodontitis and systemic diseases: a record of discussions of working group 4 of the Joint EFP/AAP Workshop on Periodontitis and Systemic Diseases
Authors: Linden Gerry J. , Herzberg Mark C. ,   on behalf of working group 4 of the joint EFP/AAP workshop
Published: May 2013

Background: There has been an explosion in research into possible associations between periodontitis and various systemic diseases and conditions.

Aim: To review the evidence for associations between periodontitis and various systemic diseases and conditions, including chronic obstructive pulmonary disease (COPD), pneumonia, chronic kidney disease, rheumatoid arthritis, cognitive impairment, obesity, metabolic syndrome and cancer, and to document headline discussions of the state of each field. Periodontal associations with diabetes, cardiovascular disease and adverse pregnancy outcomes were not discussed by working group 4.

Results: Working group 4 recognized that the studies performed to date were largely cross‐sectional or case‐control with few prospective cohort studies and no randomized clinical trials. The best current evidence suggests that periodontitis is characterized by both infection and pro‐inflammatory events, which variously manifest within the systemic diseases and disorders discussed. Diseases with at least minimal evidence of an association with periodontitis include COPD, pneumonia, chronic kidney disease, rheumatoid arthritis, cognitive impairment, obesity, metabolic syndrome and cancer. The working group agreed that there is insufficient evidence to date to infer causal relationships with the exception that organisms originating in the oral microbiome can cause lung infections.

Conclusions: The group was unanimous in their opinion that the reported associations do not imply causality, and establishment of causality will require new studies that fulfil the Bradford Hill or equivalent criteria. Precise and community‐agreed case definitions of periodontal disease states must be implemented systematically to enable consistent and clearer interpretations of studies of the relationship to systemic diseases. The members of the working group were unanimous in their opinion that to develop data that best inform clinicians, investigators and the public, studies should focus on robust disease outcomes and avoid surrogate endpoints. It was concluded that because of the relative immaturity of the body of evidence for each of the purported relationships, the field is wide open and the gaps in knowledge are large.
Inflammatory mechanisms linking periodontal diseases to cardiovascular diseases
Authors: Schenkein Harvey A. , Loos Bruno G.
Published: May 2013

Aims: In this article, inflammatory mechanisms that link periodontal diseases to cardiovascular diseases are reviewed. Methods: This article is a literature review.

Results: Studies in the literature implicate a number of possible mechanisms that could be responsible for increased inflammatory responses in atheromatous lesions due to periodontal infections. These include increased systemic levels of inflammatory mediators stimulated by bacteria and their products at sites distant from the oral cavity, elevated thrombotic and hemostatic markers that promote a prothrombotic state and inflammation, cross‐reactive systemic antibodies that promote inflammation and interact with the atheroma, promotion of dyslipidemia with consequent increases in pro‐inflammatory lipid classes and subclasses, and common genetic susceptibility factors present in both disease leading to increased inflammatory responses.

Conclusions: Such mechanisms may be thought to act in concert to increase systemic inflammation in periodontal disease and to promote or exacerbate atherogenesis. However, proof that the increase in systemic inflammation attributable to periodontitis impacts inflammatory responses during atheroma development, thrombotic events or myocardial infarction or stroke is lacking.
The epidemiological evidence behind the association between periodontitis and incident atherosclerotic cardiovascular disease
Authors: Dietrich Thomas , Sharma Praveen , Walter Clemens , Weston Paul , Beck James
Published: May 2013

Objectives: The objective of this study was to systematically review the epidemiological evidence for an association between periodontitis (PD) and incident atherosclerotic cardiovascular disease (ACVD), including coronary heart disease (CHD), cerebrovascular disease and peripheral arterial disease.

Methods: Systematic review of cohort and case‐control studies on the association of clinically or radiographically diagnosed PD and ACVD.

Results: Overall, 12 studies were included in this study (six studies on CHD, three studies on cerebrovascular disease, two studies on both coronary heart and cerebrovascular disease mortality and one study on peripheral arterial disease).All but one study reported positive associations between various periodontal disease measures and the incidence of ACVD, at least in specific subgroups. The association was stronger in younger adults and there was no evidence for an association between PD and incident CHD in subjects older than 65 years. Only one study evaluated the association between PD and secondary cardiovascular events.

Conclusions: There is evidence for an increased risk of ACVD in patients with PD compared to patients without. However, this may not apply to all groups of the population. There is insufficient evidence for an association between PD and the incidence of secondary cardiovascular events.
Managerial Incentives and Management Forecast Precision
Authors: Cheng Qiang , Luo Ting , Yue Heng
Published: May 2013

Managers have great discretion in determining forecast characteristics, but little is known about how managerial incentives affect these characteristics. This paper examines whether managers strategically choose forecast precision for self-serving purposes. Building on the prior finding that the market reaction to vague forecasts is weaker than its reaction to precise forecasts, we find that for management forecasts disclosed before insider sales, more positive (negative) news forecasts are more (less) precise than other management forecasts. The opposite applies to management forecasts disclosed before insider purchases. These results are consistent with managers strategically choosing forecast precision to increase stock prices before insider sales and to decrease stock prices before insider purchases. Additional analyses indicate that the impact of managerial incentives on forecast precision is less pronounced when institutional ownership is high or when disclosure risk is high, and is more pronounced when investors have difficulty in assessing the precision of managers' information.

Data Availability: The data used in this study are publicly available from the sources indicated in the text.