bluuebunny/crossref_metadata_2025 huggingface dataset:
Distinct Roles of Bulbar Muscarinic and Nicotinic Receptors in Olfactory Discrimination Learning
Authors: Devore Sasha , de Almeida Licurgo , Linster Christiane
Published: September 2014

The olfactory bulb (OB) and piriform cortex receive dense cholinergic projections from the basal forebrain. Cholinergic modulation within the piriform cortex has long been proposed to serve important functions in olfactory learning and memory. We here investigate how olfactory discrimination learning is regulated by cholinergic modulation of the OB inputs to the piriform cortex. We examined rats' performance on a two-alternative choice odor discrimination task following local, bilateral blockade of cholinergic nicotinic and/or muscarinic receptors in the OB. Results demonstrate that acquisition, but not recall, of novel discrimination problems is impaired following blockade of OB cholinergic receptors, although the relative contribution of muscarinic and nicotinic receptors depends on task difficulty. Blocking muscarinic receptors impairs learning for nearly all odor sets, whereas blocking nicotinic receptors only affects performance for perceptually similar odors. This pattern of behavioral effects is consistent with predictions from a model of cholinergic modulation in the OB and piriform cortex (de Almeida et al., 2013). Model simulations suggest that muscarinic and nicotinic receptors may serve complementary roles in regulating coherence and sparseness of the OB network output, which in turn differentially regulate the strength and overlap in cortical odor representations. Overall, our results suggest that muscarinic receptor blockade results in abona fidelearning impairment that may arise because cortical neurons are activated less often. Behavioral impairment following nicotinic receptor blockade may not be due to the inability of the cortex to learn, but rather arises because the cortex is unable to resolve highly overlapping input patterns.
A Critical Role for Interferon Regulatory Factor 9 in Cerebral Ischemic Stroke
Authors: Chen Hou-Zao , Guo Sen , Li Zuo-Zhi , Lu Yanyun , Jiang Ding-Sheng , Zhang Ran , Lei Hao , Gao Lu , Zhang Xiaofei , Zhang Yan , Wang Lang , Zhu Li-Hua , Xiang Mei , Zhou Yan , Wan Qi , Dong Hailong , Liu De-Pei , Li Hongliang
Published: September 2014

The failure of past efforts to develop effective stroke treatments is at least partially because these treatments often interfered with essential physiological functions, even though they are targeted toward pathophysiological events, such as inflammation, excitotoxicity, and oxidative stress. Thus, the direct targeting of endogenous neuroprotective or destructive elements holds promise as a potential new approach to treating this devastating condition. Interferon regulatory factor 9 (IRF9), a transcription factor that regulates innate immune responses, has been implicated in neurological pathology. Here, we provide new evidence that IRF9 directly mediates neuronal death in male mice. In response to ischemia/reperfusion (I/R), IRF9 accumulated in neurons. IRF9 deficiency markedly mitigated both poststroke neuronal death and neurological deficits, whereas the neuron-specific overexpression of IRF9 sensitized neurons to death. The histone deacetylase Sirt1 was identified as a novel negative transcriptional target of IRF9 bothin vivoandin vitro. IRF9 inhibits Sirt1 deacetylase activity, culminating in the acetylation and activation of p53-mediated cell death signaling. Importantly, both the genetic and pharmacological manipulation of Sirt1 effectively counteracted the pathophysiological effects of IRF9 on stroke outcome. These findings indicate that, rather than activating a delayed innate immune response, IRF9 directly activates neuronal death signaling pathways through the downregulation of Sirt1 deacetylase in response to acute I/R stress.
Network Organization Unfolds over Time during Periods of Anxious Anticipation
Authors: McMenamin Brenton W. , Langeslag Sandra J.E. , Sirbu Mihai , Padmala Srikanth , Pessoa Luiz
Published: September 2014

Entering a state of anxious anticipation triggers widespread changes across large-scale networks in the brain. The temporal aspects of this transition into an anxious state are poorly understood. To address this question, an instructed threat of shock paradigm was used while recording functional MRI in humans to measure how activation and functional connectivity change over time across the salience, executive, and task-negative networks and how they interact with key regions implicated in emotional processing; the amygdala and bed nucleus of the stria terminalis (BNST). Transitions into threat blocks were associated with transient responses in regions of the salience network and sustained responses in a putative BNST site, among others. Multivariate network measures of communication were computed, revealing changes to network organization during transient and sustained periods of threat, too. For example, the salience network exhibited a transient increase in network efficiency followed by a period of sustained decreased efficiency. The amygdala became more central to network function (as assessed via betweenness centrality) during threat across all participants, and the extent to which the BNST became more central during threat depended on self-reported anxiety. Together, our study unraveled a progression of responses and network-level changes due to sustained threat. In particular, our results reveal how network organization unfolds with time during periods of anxious anticipation.
Threonine 149 Phosphorylation Enhances ΔFosB Transcriptional Activity to Control Psychomotor Responses to Cocaine
Authors: Cates Hannah M. , Thibault Mackenzie , Pfau Madeline , Heller Elizabeth , Eagle Andrew , Gajewski Paula , Bagot Rosemary , Colangelo Christopher , Abbott Thomas , Rudenko Gabby , Neve Rachael , Nestler Eric J. , Robison Alfred J.
Published: September 2014

Stable changes in neuronal gene expression have been studied as mediators of addicted states. Of particular interest is the transcription factor ΔFosB, a truncated and stableFosBgene product whose expression in nucleus accumbens (NAc), a key reward region, is induced by chronic exposure to virtually all drugs of abuse and regulates their psychomotor and rewarding effects. Phosphorylation at Ser27contributes to ΔFosB's stability and accumulation following repeated exposure to drugs, and our recent work demonstrates that the protein kinase CaMKIIα phosphorylates ΔFosB at Ser27and regulates its stabilityin vivo. Here, we identify two additional sites on ΔFosB that are phosphorylatedin vitroby CaMKIIα, Thr149and Thr180, and demonstrate their regulationin vivoby chronic cocaine. We show that phosphomimetic mutation of Thr149(T149D) dramatically increases AP-1 transcriptional activity while alanine mutation does not affect transcriptional activity when compared with wild-type (WT) ΔFosB. Usingin vivoviral-mediated gene transfer of ΔFosB-T149D or ΔFosB-T149A in mouse NAc, we determined that overexpression of ΔFosB-T149D in NAc leads to greater locomotor activity in response to an initial low dose of cocaine than does WT ΔFosB, while overexpression of ΔFosB-T149A does not produce the psychomotor sensitization to chronic low-dose cocaine seen after overexpression of WT ΔFosB and abrogates the sensitization seen in control animals at higher cocaine doses. We further demonstrate that mutation of Thr149does not affect the stability of ΔFosB overexpressed in mouse NAc, suggesting that the behavioral effects of these mutations are driven by their altered transcriptional properties.
Thalamic NMDA Receptor Function Is Necessary for Patterning of the Thalamocortical Somatosensory Map and for Sensorimotor Behaviors
Authors: Arakawa Hiroyuki , Suzuki Ayumi , Zhao Shuxin , Tsytsarev Vassiliy , Lo Fu-Sun , Hayashi Yu , Itohara Shigeyoshi , Iwasato Takuji , Erzurumlu Reha S.
Published: September 2014

NMDARs play a major role in patterning of topographic sensory maps in the brain. Genetic knock-out of the essential subunit of NMDARs in excitatory cortical neurons prevents whisker-specific neural pattern formation in the barrel cortex. To determine the role of NMDARs en route to the cortex, we generated sensory thalamus-specific NR1 (Grin1)-null mice (ThNR1KO). A multipronged approach, using histology, electrophysiology, optical imaging, and behavioral testing revealed that, in these mice, whisker patterns develop in the trigeminal brainstem but do not develop in the somatosensory thalamus. Subsequently, there is no barrel formation in the neocortex yet a partial afferent patterning develops. Whisker stimulation evokes weak cortical activity and presynaptic neurotransmitter release probability is also affected. We found several behavioral deficits in tasks, ranging from sensorimotor to social and cognitive. Collectively, these results show that thalamic NMDARs play a critical role in the patterning of the somatosensory thalamic and cortical maps and their impairment may lead to pronounced behavioral defects.
Neural Cell Adhesion Molecule NrCAM Regulates Semaphorin 3F-Induced Dendritic Spine Remodeling
Authors: Demyanenko Galina P. , Mohan Vishwa , Zhang Xuying , Brennaman Leann H. , Dharbal Katherine E.S. , Tran Tracy S. , Manis Paul B. , Maness Patricia F.
Published: September 2014

Neuron-glial related cell adhesion molecule (NrCAM) is a regulator of axon growth and repellent guidance, and has been implicated in autism spectrum disorders. Here a novel postsynaptic role for NrCAM in Semaphorin3F (Sema3F)-induced dendritic spine remodeling was identified in pyramidal neurons of the primary visual cortex (V1). NrCAM localized to dendritic spines of star pyramidal cells in postnatal V1, where it was coexpressed with Sema3F. NrCAM deletion in mice resulted in elevated spine densities on apical dendrites of star pyramidal cells at both postnatal and adult stages, and electron microscopy revealed increased numbers of asymmetric synapses in layer 4 of V1. Whole-cell recordings in cortical slices from NrCAM-null mice revealed increased frequency of mEPSCs in star pyramidal neurons. Recombinant Sema3F-Fc protein induced spine retraction on apical dendrites of wild-type, but not NrCAM-null cortical neurons in culture, while re-expression of NrCAM rescued the spine retraction response. NrCAM formed a complex in brain with Sema3F receptor subunits Neuropilin-2 (Npn-2) and PlexinA3 (PlexA3) through an Npn-2-binding sequence (TARNER) in the extracellular Ig1 domain. Atransheterozygous genetic interaction test demonstrated that Sema3F and NrCAM pathways interactedin vivoto regulate spine density in star pyramidal neurons. These findings reveal NrCAM as a novel postnatal regulator of dendritic spine density in cortical pyramidal neurons, and an integral component of the Sema3F receptor complex. The results implicate NrCAM as a contributor to excitatory/inhibitory balance in neocortical circuits.
Intermittent Theta-Burst Stimulation of the Lateral Cerebellum Increases Functional Connectivity of the Default Network
Authors: Halko Mark A. , Farzan Faranak , Eldaief Mark C. , Schmahmann Jeremy D. , Pascual-Leone Alvaro
Published: September 2014

Cerebral cortical intrinsic connectivity networks share topographically arranged functional connectivity with the cerebellum. However, the contribution of cerebellar nodes to distributed network organization and function remains poorly understood. In humans, we applied theta-burst transcranial magnetic stimulation, guided by subject-specific connectivity, to regions of the cerebellum to evaluate the functional relevance of connections between cerebellar and cerebral cortical nodes in different networks. We demonstrate that changing activity in the human lateral cerebellar Crus I/II modulates the cerebral default mode network, whereas vermal lobule VII stimulation influences the cerebral dorsal attention system. These results provide novel insights into the distributed, but anatomically specific, modulatory impact of cerebellar effects on large-scale neural network function.
Role of Bed Nucleus of the Stria Terminalis Corticotrophin-Releasing Factor Receptors in Frustration Stress-Induced Binge-Like Palatable Food Consumption in Female Rats with a History of Food Restriction
Authors: Micioni Di Bonaventura Maria Vittoria , Ciccocioppo Roberto , Romano Adele , Bossert Jennifer M. , Rice Kenner C. , Ubaldi Massimo , St. Laurent Robyn , Gaetani Silvana , Massi Maurizio , Shaham Yavin , Cifani Carlo
Published: September 2014

We developed recently a binge-eating model in which female rats with a history of intermittent food restriction show binge-like palatable food consumption after 15 min exposure to the sight of the palatable food. This “frustration stress” manipulation also activates the hypothalamic–pituitary–adrenal stress axis. Here, we determined the role of the stress neurohormone corticotropin-releasing factor (CRF) in stress-induced binge eating in our model. We also assessed the role of CRF receptors in the bed nucleus of the stria terminalis (BNST), a brain region implicated in stress responses and stress-induced drug seeking, in stress-induced binge eating. We used four groups that were first exposed or not exposed to repeated intermittent cycles of regular chow food restriction during which they were also given intermittent access to high-caloric palatable food. On the test day, we either exposed or did not expose the rats to the sight of the palatable food for 15 min (frustration stress) before assessing food consumption for 2 h. We found that systemic injections of the CRF1 receptor antagonist R121919 (2,5-dimethyl-3-(6-dimethyl-4-methylpyridin-3-yl)-7 dipropylamino pyrazolo[1,5-a]pyrimidine) (10–20 mg/kg) and BNST (25–50 ng/side) or ventricular (1000 ng) injections of the nonselective CRF receptor antagonistd-Phe-CRF(12–41)decreased frustration stress-induced binge eating in rats with a history of food restriction. Frustration stress also increased Fos (a neuronal activity marker) expression in ventral and dorsal BNST. Results demonstrate a critical role of CRF receptors in BNST in stress-induced binge eating in our rat model. CRF1 receptor antagonists may represent a novel pharmacological treatment for bingeing-related eating disorders.
Role of the Dorsal Medial Habenula in the Regulation of Voluntary Activity, Motor Function, Hedonic State, and Primary Reinforcement
Authors: Hsu Yun-Wei A. , Wang Si D. , Wang Shirong , Morton Glenn , Zariwala Hatim A. , de la Iglesia Horacio O. , Turner Eric E.
Published: September 2014

The habenular complex in the epithalamus consists of distinct regions with diverse neuronal populations. Past studies have suggested a role for the habenula in voluntary exercise motivation and reinforcement of intracranial self-stimulation but have not assigned these effects to specific habenula subnuclei. Here, we have developed a genetic model in which neurons of the dorsal medial habenula (dMHb) are developmentally eliminated, via tissue-specific deletion of the transcription factorPou4f1(Brn3a). Mice with dMHb lesions perform poorly in motivation-based locomotor behaviors, such as voluntary wheel running and the accelerating rotarod, but show only minor abnormalities in gait and balance and exhibit normal levels of basal locomotion. These mice also show deficits in sucrose preference, but not in the forced swim test, two measures of depression-related phenotypes in rodents. We have also used Cre recombinase-mediated expression of channelrhodopsin-2 and halorhodopsin to activate dMHb neurons or silence their output in freely moving mice, respectively. Optical activation of the dMHbin vivosupports intracranial self-stimulation, showing that dMHb activity is intrinsically reinforcing, whereas optical silencing of dMHb outputs is aversive. Together, our findings demonstrate that the dMHb is involved in exercise motivation and the regulation of hedonic state, and is part of an intrinsic reinforcement circuit.
TDP-43 Toxicity Proceeds via Calcium Dysregulation and Necrosis in AgingCaenorhabditis elegansMotor Neurons
Authors: Aggad Dina , Vérièpe Julie , Tauffenberger Arnaud , Parker J. Alex
Published: September 2014

Amyotrophic lateral sclerosis (ALS) is a heterogeneous disease with either sporadic or genetic origins characterized by the progressive degeneration of motor neurons. At the cellular level, ALS neurons show protein misfolding and aggregation phenotypes. Transactive response DNA-binding protein 43 (TDP-43) has recently been shown to be associated with ALS, but the early pathophysiological deficits causing impairment in motor function are unknown. Here we usedCaenorhabditis elegansexpressing mutant TDP-43A315Tin motor neurons and explored the potential influences of calcium (Ca2+). Using chemical and genetic approaches to manipulate the release of endoplasmic reticulum (ER) Ca2+stores, we observed that the reduction of intracellular Ca2+([Ca2+]i) rescued age-dependent paralysis and prevented the neurodegeneration of GABAergic motor neurons. Our data implicate elevated [Ca2+]ias a driver of TDP-43-mediated neuronal toxicity. Furthermore, we discovered that neuronal degeneration is independent of the executioner caspase CED-3, but instead requires the activity of the Ca2+-regulated calpain protease TRA-3, and the aspartyl protease ASP-4. Finally, chemically blocking protease activity protected against mutant TDP-43A315T-associated neuronal toxicity. This work both underscores the potential of theC. eleganssystem to identify key targets for therapeutic intervention and suggests that a focused effort to regulate ER Ca2+release and necrosis-like degeneration consequent to neuronal injury may be of clinical importance.
The Neural Code for Face Orientation in the Human Fusiform Face Area
Authors: Ramírez Fernando M. , Cichy Radoslaw M. , Allefeld Carsten , Haynes John-Dylan
Published: September 2014

Humans recognize faces and objects with high speed and accuracy regardless of their orientation. Recent studies have proposed that orientation invariance in face recognition involves an intermediate representation where neural responses are similar for mirror-symmetric views. Here, we used fMRI, multivariate pattern analysis, and computational modeling to investigate the neural encoding of faces and vehicles at different rotational angles. Corroborating previous studies, we demonstrate a representation of face orientation in the fusiform face-selective area (FFA). We go beyond these studies by showing that this representation is category-selective and tolerant to retinal translation. Critically, by controlling for low-level confounds, we found the representation of orientation in FFA to be compatible with a linear angle code. Aspects of mirror-symmetric coding cannot be ruled out when FFA mean activity levels are considered as a dimension of coding. Finally, we used a parametric family of computational models, involving a biased sampling of view-tuned neuronal clusters, to compare different face angle encoding models. The best fitting model exhibited a predominance of neuronal clusters tuned to frontal views of faces. In sum, our findings suggest a category-selective and monotonic code of face orientation in the human FFA, in line with primate electrophysiology studies that observed mirror-symmetric tuning of neural responses at higher stages of the visual system, beyond the putative homolog of human FFA.
Prismatic Adaptation Changes Visuospatial Representation in the Inferior Parietal Lobule
Authors: Crottaz-Herbette Sonia , Fornari Eleonora , Clarke Stephanie
Published: September 2014

Prismatic adaptation has been shown to induce a realignment of visuoproprioceptive representations and to involve parietocerebellar networks. We have investigated in humans how far other types of functions known to involve the parietal cortex are influenced by a brief exposure to prismatic adaptation. Normal subjects underwent an fMRI evaluation before and after a brief session of prismatic adaptation using rightward deviating prisms for one group or after an equivalent session using plain glasses for the other group. Activation patterns to three tasks were analyzed: (1) visual detection; (2) visuospatial short-term memory; and (3) verbal short-term memory. The prismatic adaptation-related changes were found bilaterally in the inferior parietal lobule when prisms, but not plain glasses, were used. This effect was driven by selective changes during the visual detection task: an increase in neural activity was induced on the left and a decrease on the right parietal side after prismatic adaptation. Comparison of activation patterns after prismatic adaptation on the visual detection task demonstrated a significant increase of the ipsilateral field representation in the left inferior parietal lobule and a significant decrease in the right inferior parietal lobule. In conclusion, a brief exposure to prismatic adaptation modulates differently left and right parietal activation during visual detection but not during short-term memory. Furthermore, the visuospatial representation within the inferior parietal lobule changes, with a decrease of the ipsilateral hemifield representation on the right and increase on the left side, suggesting thus a left hemispheric dominance.
Spinal Cord Injury Enables Aromatic l-Amino Acid Decarboxylase Cells to Synthesize Monoamines
Authors: Wienecke Jacob , Ren Li-Qun , Hultborn Hans , Chen Meng , Møller Morten , Zhang Yifan , Zhang Mengliang
Published: September 2014

Serotonin (5-HT), an important modulator of both sensory and motor functions in the mammalian spinal cord, originates mainly in the raphe nuclei of the brainstem. However, following complete transection of the spinal cord, small amounts of 5-HT remain detectable below the lesion. It has been suggested, but not proven, that this residual 5-HT is produced by intraspinal 5-HT neurons. Here, we show by immunohistochemical techniques that cells containing the enzyme aromaticl-amino acid decarboxylase (AADC) occur not only near the central canal, as reported by others, but also in the intermediate zone and dorsal horn of the spinal gray matter. We show that, following complete transection of the rat spinal cord at S2 level, AADC cells distal to the lesion acquire the ability to produce 5-HT from its immediate precursor, 5-hydroxytryptophan. Our results indicate that this phenotypic change in spinal AADC cells is initiated by the loss of descending 5-HT projections due to spinal cord injury (SCI). Byin vivoandin vitroelectrophysiology, we show that 5-HT produced by AADC cells increases the excitability of spinal motoneurons. The phenotypic change in AADC cells appears to result from a loss of inhibition by descending 5-HT neurons and to be mediated by 5-HT1B receptors expressed by AADC cells. These findings indicate that AADC cells are a potential source of 5-HT at spinal levels below an SCI. The production of 5-HT by AADC cells, together with an upregulation of 5-HT2 receptors, offers a partial explanation of hyperreflexia below a chronic SCI.
Developmental Profiles of the Intrinsic Properties and Synaptic Function of Auditory Neurons in Preterm and Term Baboon Neonates
Authors: Kim Sei Eun , Lee Seul Yi , Blanco Cynthia L. , Kim Jun Hee
Published: September 2014

The human fetus starts to hear and undergoes major developmental changes in the auditory system during the third trimester of pregnancy. Although there are significant data regarding development of the auditory system in rodents, changes in intrinsic properties and synaptic function of auditory neurons in developing primate brain at hearing onset are poorly understood. We performed whole-cell patch-clamp recordings of principal neurons in the medial nucleus of trapezoid body (MNTB) in preterm and term baboon brainstem slices to study the structural and functional maturation of auditory synapses. Each MNTB principal neuron received an excitatory input from a single calyx of Held terminal, and this one-to-one pattern of innervation was already formed in preterm baboons delivered at 67% of normal gestation. There was no difference in frequency or amplitude of spontaneous excitatory postsynaptic synaptic currents between preterm and term MNTB neurons. In contrast, the frequency of spontaneous GABAA/glycine receptor-mediated inhibitory postsynaptic synaptic currents, which were prevalent in preterm MNTB neurons, was significantly reduced in term MNTB neurons. Preterm MNTB neurons had a higher input resistance than term neurons and fired in bursts, whereas term MNTB neurons fired a single action potential in response to suprathreshold current injection. The maturation of intrinsic properties and dominance of excitatory inputs in the primate MNTB allow it to take on its mature role as a fast and reliable relay synapse.
Frequency-Dependent, Cell Type-Divergent Signaling in the Hippocamposeptal Projection
Authors: Mattis Joanna , Brill Julia , Evans Suzanne , Lerner Talia N. , Davidson Thomas J. , Hyun Minsuk , Ramakrishnan Charu , Deisseroth Karl , Huguenard John R.
Published: September 2014

Hippocampal oscillations are critical for information processing, and are strongly influenced by inputs from the medial septum. Hippocamposeptal neurons provide direct inhibitory feedback from the hippocampus onto septal cells, and are therefore likely to also play an important role in the circuit; these neurons fire at either low or high frequency, reflecting hippocampal network activity during theta oscillations or ripple events, respectively. Here, we optogenetically target the long-range GABAergic projection from the hippocampus to the medial septum in rats, and thereby simulate hippocampal input onto downstream septal cells in an acute slice preparation. In response to optogenetic activation of hippocamposeptal fibers at theta and ripple frequencies, we elicit postsynaptic GABAergic responses in a subset (24%) of septal cells, most predominantly in fast-spiking cells. In addition, in another subset of septal cells (19%) corresponding primarily to cholinergic cells, we observe a slow hyperpolarization of the resting membrane potential and a decrease in input resistance, particularly in response to prolonged high-frequency (ripple range) stimulation. This slow response is partially sensitive to GIRK channel and D2 dopamine receptor block. Our results suggest that two independent populations of septal cells distinctly encode hippocampal feedback, enabling the septum to monitor ongoing patterns of activity in the hippocampus.
Fine-Scale Plasticity of Microscopic Saccades
Authors: Havermann Katharina , Cherici Claudia , Rucci Michele , Lappe Markus
Published: September 2014

When asked to maintain their gaze steady on a given location, humans continually perform microscopic eye movements, including fast gaze shifts known as microsaccades. It has long been speculated that these movements may contribute to the maintenance of fixation, but evidence has remained contradictory. We used a miniaturized version of saccadic adaptation, an experimental procedure by which motor control of saccades is modified through intrasaccadic displacements of the target. We found that the statistical distribution of microsaccade amplitudes changes after brief exposure to systematic shifts of the fixation point during microsaccade occurrence. Shifts in the same directions as microsaccades produce movements with larger amplitudes, whereas shifts against microsaccade directions result in smaller movements. Our findings show that microsaccades are precisely monitored during fixation and that their motor program is modified if the postsaccadic target position is not at the expected retinal location. These results demonstrate that saccadic adaptation occurs even when the stimulus is already close to the foveal center and precise execution of the movement may not be critical. They support the proposal that adaptation is necessary to maintain a consistent relationship between motor control and its visual consequences and that the representation of space is intrinsically multimodal, even during fixation.
Reference Genes for Expression Studies in Hypoxia and Hyperglycemia Models in Human Umbilical Vein Endothelial Cells
Authors: Bakhashab Sherin , Lary Sahira , Ahmed Farid , Schulten Hans-Juergen , Bashir Ayat , Ahmed Fahad W , Al-Malki Abdulrahman L , Jamal Hasan S , Gari Mamdooh A , Weaver Jolanta U
Published: September 2014

Human umbilical vein endothelial cell (HUVEC)-based gene expression studies performed under hypoxia and/or hyperglycemia show huge potential for modeling endothelial cell response in cardiovascular disease and diabetes. However, such studies require reference genes that are stable across the whole range of experimental conditions. These reference genes have not been comprehensively defined to date. We applied human genome-wide microarrays and quantitative real-time PCR (qRT-PCR) on RNA obtained from primary HUVEC cultures that were incubated for 24 hr either in euglycemic or in hyperglycemic conditions and then subjected to short-term CoCl2-induced hypoxia for 1, 3, or 12 hr. Using whole-transcript arrays, we selected 10 commonly used reference genes with no significant expression variation across eight different conditions. These genes were ranked using NormFinder software according to their stability values. Consequently, five genes were selected for validation by qRT-PCR. These were ribosomal protein large P0 (RPLP0), transferrin receptor (TFRC), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), β-glucuronidase (GUSB), and β-actin (ACTB). All five genes displayed stable expression under hyperglycemia. However, only RPLP0 and TFRC genes were stable under hypoxia up to 12 hr. Under hyperglycemia combined with hypoxia up to 12 hr, the expression of RPLP0, TFRC, GUSB, and ACTB genes remained unchanged. Our findings strongly confirm that RPLP0 and TFRC are the most suitable reference genes for HUVEC gene expression experiments subjected to hypoxia and/or hyperglycemia for the given experimental conditions. We provide further evidence that even commonly known references genes require experimental validation for all conditions involved.
Whole-Genome Expression Analysis in the Third Instar Larval Midgut of Drosophila melanogaster
Authors: Harrop Thomas W R , Pearce Stephen L , Daborn Phillip J , Batterham Philip
Published: September 2014

Survival of insects on a substrate containing toxic substances such as plant secondary metabolites or insecticides is dependent on the metabolism or excretion of those xenobiotics. The primary sites of xenobiotic metabolism are the midgut, Malpighian tubules, and fat body. In general, gene expression in these organs is reported for the entire tissue by online databases, but several studies have shown that gene expression within the midgut is compartmentalized. Here, RNA sequencing is used to investigate whole-genome expression in subsections of third instar larval midguts of Drosophila melanogaster. The data support functional diversification in subsections of the midgut. Analysis of the expression of gene families that are implicated in the metabolism of xenobiotics suggests that metabolism may not be uniform along the midgut. These data provide a starting point for investigating gene expression and xenobiotic metabolism and other functions of the larval midgut.
Li Storage on TCNE and TCNE-(Doped)-Graphene Complexes: a Computational Study
Authors: Chen Yingqian , Manzhos Sergei
Published: September 2014

Li attachment to free tetracyanoethylene (TCNE) molecules and TCNE adsorbed on doped graphene is studied using density functional theory. While TCNE is adsorbed only weakly on ideal graphene, we identified a configuration in which TCNE is chemisorbed on Al-doped graphene via its C atom and a surface oxygen atom. Up to four Li atoms can be stored on both free and adsorbed TCNE with binding energies stronger than cohesive energy of the Li metal. TCNE immobilized on the conducting graphene-based substrate could therefore become an efficient anode material for organic Li ion batteries.
Código de ética: os elementos essenciais na visão de uma empresa do setor sucroalcooleiro do interior de São Paulo
Authors: Santos Maristane Aparecida Pinheiro , Galli Lesley Carina do Lago Attadia , Galli Rafael Altafin , Santos David Ferreira Lopes
Published: September 2014

Ética e principalmente o código de ética são assuntos amplamente discutidos e exigidos no âmbito organizacional, sendo a elaboração e aplicação do código de ética uma tarefa que exige empenho e dedicação por parte das empresas, sendo que o mesmo deve ser coerente com a cultura organizacional, missão, visão e valores. Dentro deste contexto, este trabalho tem como objetivo identificar quais são os aspectos mais relevantes na concepção do código de ética de uma organização. Para tanto foi realizado um estudo de caso de caráter exploratório-descritivo e abordagem qualitativa em uma organização do setor sucroalcooleiro. Como resultados teóricos verificou-se que para ser eficiente um código de ética deve contemplar todos os seus stakeholders. Em relação à empresa analisada, observa-se que o código de ética apresenta definições claras e objetivas de como deve ser seu relacionamento com seus stakeholders. Todavia nota-se uma ênfase maior no que tange às diretrizes em relação ao comportamento dos colaboradores, em detrimento dos demais stakeholders. Palavras-chave: Ética. Código de Ética. Gestão de Organizações.
Classificação de Portfólio de Créditos Não-Performados utilizando Redes Neurais Artificiais Multilayer Perceptron
Authors: Clesio Flavio , Sassi Renato José
Published: September 2014

O objetivo da presente pesquisa é realizar a aplicação da técnica de redes neurais do tipo Multilayer Perceptron (MLP) na criação dos modelos classificação de um portfólio de créditos inadimplidos não-performados (NPLs – Non-Performing Loans) para classificação destes derivativos de crédito. Os créditos NPL são caracterizados como o montante relativo a empréstimos que não foram pagos e que já estão vencidos por mais de 90 dias. Uma vez que esses títulos por força de legislação são movidos para perdas, Fundos de Investimento em Direitos Creditórios (FIDC) realizam a compra dessas dívidas junto a essas instituições e realizam o processo de recuperação desse crédito. Com a utilização de redes neurais foram criados modelos de classificação relativos à posterior recuperação dessas dívidas. Para a avaliação de desempenho dos modelos foram apresentadas métricas de avaliação da classificação relativas às redes neurais com diferentes arquiteturas. Os resultados com a classificação foram satisfatórios tendo em vista que os modelos de classificação tiveram sucesso conforme a estrutura de custos econômicos apresentada. Palavras-chave: Créditos Não-Performados. Redes Neurais Artificiais. Multilayer Perceptron. Non-Performing Loans. Créditos Inadimplidos.
Diagnóstico do nível de maturidade do processo de desenvolvimento de produtos: um estudo de caso em empresa calçadista
Authors: Maganha Murilo Roberto Jesus , Rodrigues José de Souza , Jugend Daniel , Leoni Juliene Navas
Published: September 2014

O processo de desenvolvimento de produtos (PDP) é um fator estratégico no qual as empresas buscam identificar necessidades dos consumidores. A relação das práticas adotadas, ferramentas, técnicas entre outros, pode determinar o nível de maturidade da empresa nesse processo. O objetivo deste artigo consiste em compreender e diagnosticar o nível de maturidade do PDP em indústria do segmento de calçados. Para o estudo de caso, foi pesquisada uma empresa que está inserida em um dos maiores polos de calçados femininos do Brasil, localizado na cidade de Jaú, Estado de São Paulo. O diagnóstico tem base nos níveis de maturidade do modelo unificado, de referência no processo de desenvolvimento de produtos, proposto por Rozenfeld et al. (2006). A aplicação do modelo auxiliou a diagnosticar o nível de maturidade atual da empresa nesse processo, fornecendo informações úteis para alcançar patamares de maturidade maior no PDP. Palavras-chave: Níveis de Maturidade. Processo de Desenvolvimento de Produtos. Modelo Unificado de Referência.
Ampliação da visão de indicadores para projetos: foco em equipes virtuais
Authors: Vargas Neto Durval Mescua , Patah Leandro Alves
Published: September 2014

É fato que a globalização torna o mercado cada vez mais competitivo e exige das empresas uma gestão eficaz. Neste cenário, o gerenciamento de projetos auxilia as empresas a atingirem suas estratégias referentes às exigências do século 21. Os indicadores ajudam os stakeholders a avaliar se os projetos estão sendo executados conforme o planejado, e quando necessário, apoiam as decisões do gerente de projeto para corrigir sua direção. O principal objetivo deste estudo é identificar os principais indicadores de projetos que utilizam equipes virtuais. A estratégia metodológica adotada foi o estudo de caso único, em uma empresa internacional de consultoria. Foi aplicado um questionário composto de um conjunto de indicadores de projetos abordado na literatura, a dezenove responsáveis por projetos. A partir da análise estatística dos dados obtidos, encontrou-se que os indicadores mais relevantes utilizados para avaliar esse tipo de projeto são os tradicionais de custo, prazo e escopo, acrescidos de alguns que levam em conta a visão do cliente e outros relacionados aos aspectos humanos e de comunicação da equipe do projeto.
Os princípios de governança corporativa e a atuação das ouvidorias em instituições bancárias no Brasil
Authors: Alves Carlos André de Melo , Machado Filho Claudio Antonio Pinheiro
Published: September 2014

O objetivo deste estudo é investigar a associação entre os princípios de governança corporativa e a atuação das ouvidorias em instituições bancárias no Brasil. Realiza-se revisão bibliográfica e pesquisa de campo, coletando-se opiniões de uma amostra de especialistas, selecionados por participarem de eventos ligados à área de ouvidoria entre 2009 e 2011 no Brasil. A análise considera 192 notas a respeito da situação atual e ideal referente a quatro princípios disseminados pelo Instituto Brasileiro de Governança Corporativa – IBGC: transparência, equidade, prestação de contas e responsabilidade corporativa. Para tratar os dados emprega-se análise descritiva e análise inferencial. Resultados indicam que a situação ideal difere da atual para todos os princípios, mas a atuação das ouvidorias associada ao princípio da prestação de contas tem uma distância da situação atual para a ideal significativamente inferior à distância pertinente aos princípios da responsabilidade corporativa e da transparência. O estudo pode auxiliar reflexões de acadêmicos e demais interessados na atuação das ouvidorias como canal de última instância para atendimento em instituições bancárias no Brasil, e pode ajudar a entender o alinhamento dessa atuação aos princípios de governança corporativa.
Análise de homogeneidade de localidades da cidade do Rio de Janeiro quanto a preços de locação: um estudo de caso
Authors: Oliveira Costa Giovani Glaucio
Published: September 2014

Este artigo tem o objetivo de apresentar a aplicação da Análise de Homogeneidade como uma alternativa à análise de dados qualitativos. A Análise de Homogeneidade é uma técnica multivariada que tem duas finalidades básicas: redução de dimensionalidade e análise estrutural. O trabalho analisou valores em reais de aluguéis médios residenciais de 24 locais ou bairros da cidade do Rio de Janeiro em 2010. O estudo visa o agrupamento das localidades em função da similaridade dos seus aluguéis médios. O perfil 1, identificado, é formado pelos bairros com os aluguéis nas faixas mais baixas. A maioria dos bairros deste perfil é da zona oeste e zona norte. O perfil 2 é formado pelos bairros com os aluguéis nas faixas intermediárias. Contemplam os bairros da zona sul e barra. O perfil 3 é formado pelos bairros com os aluguéis nas faixas mais altas. Contemplam somente bairros da zona sul. Estes resultados são importantes tanto para ressaltar a importância da Análise de Homogeneidade quanto para as tomadas de decisão de administradores da área imobiliária.
Scutia buxifolia Reissek essential oil: in vitro antioxidant and antimicrobial activities
Authors: BOLIGON ALINE A. , PIANA MARIANA , BRUM THIELE F. DE , FROEDER AMANDA L.F. , BELKE BIANCA V. , SCHWANZ THIAGO G. , MARIO DÉBORA N. , ALVES SYDNEY H. , ATHAYDE MARGARETH L.
Published: September 2014

The volatile oil from the stem bark of Scutia buxifolia (Rhamnaceae) has been obtained by hydrodistillation and analyzed by GC-MS. Twenty-one components were identified representing 99.93 % of the total oil composition, spathulenol (35.87%), β-cubebene (17.26%), germacrene D (6.43%), linalool (5.19%), carvacrol (4.05%) were the main components of S. buxifolia essential oil. Antioxidant and antimicrobial properties of the essential oil were evaluated by free radical scavenging (DPPH) assay and micro broth dilution method, respectively. S. buxifolia essential oil presented interesting radical scavenging activity (IC50 = 15.03 ± 0.11 µg/mL). The antibacterial assay showed that S. buxifolia stem bark essential oil was moderately active against the Staphylococcus aureus and Micrococcus sp. (MIC = 500 µg/mL) and Escherichia coli (250 µg/mL). To the best of our knowledge, this is the first study on the composition, antioxidant and antimicrobial activities of essential oil from the S. buxifolia collected from Brazil.
Benefits of caloric restriction in the myenteric neuronal plasticity in aging rats
Authors: PEREIRA JOICE N.B. , MARI RENATA B. , STABILLE SANDRA R. , FARIA HAROLDO G. DE , MOTA THAIS F.M. , FERREIRA WALTER M.
Published: September 2014

Aging is a biologic process characterized by progressive damage of structures and functions of organic systems. In gastrointestinal tract, it can involve enteric nervous system, which plays an important role in digestion and absorption of nutrients, causing hastening of intestinal transit thus reducing its absorptive function. Caloric restriction has been used in several studies with the intention of delaying deleterious effects of aging. This study aimed to evaluate the effects of caloric restriction on myenteric neurons of ileum by aging in rats. 30 Wistar rats were grouped as follows: GI (animals aged 6 months fed with normal diet), GII (animals aged 18 months fed with normal diet) and GIII (animals aged 18 months subject to 31% of caloric restriction). The rats of the GI group were euthanized at 6 months of age and after experimental period of 12 months animals of the group GII and GIII were euthanized, the ileum of all groups were collected, measured and processed by NADPH-dp and Acetylcholinesterase. Quantitative analysis of neurons revealed that aging promotes the increasing of myenteric neurons NADPH-dp and reduces Acetylcholinesterase neuronal population. However, in the cellular profile area, were not observed significant differences between the groups. The caloric restriction has been efficient and can be used preventively because it minimizes quantitative changes associated with aging on ileum myenteric plexuses.
Structure, histochemistry and phytochemical profile of the bark of the sobol and aerial stem of Tontelea micrantha (Celastraceae - Hippocrateoideae)
Authors: MERCADANTE-SIMÕES MARIA OLÍVIA , MAZZOTTINI-DOS-SANTOS HELLEN C. , NERY LAYS A. , FERREIRA PERACIO R.B. , RIBEIRO LEONARDO M. , ROYO VANESSA A. , OLIVEIRA DARIO A. DE
Published: September 2014

The bark of the underground stem of Tontelea micrantha (Mart. ex. Schult.) A. C. Sm., a native Brazilian Cerrado species, is used in folk medicine for treating kidney ailments. The structures of the underground and the aerial stems were examined and their barks were analyzed for the presence of secondary metabolites. Bark fragments were processed according to conventional techniques in plant anatomy and their chemical compositions examined using histochemical and phytochemical tests, thin layer chromatography, and high-efficiency liquid chromatography. The underground stem is a sobol with unusual cambial activity. Laticifers that secrete terpenoids were present in the cortex and phloem of both organs and can contribute to the identification of the species in field. Druses were present in both barks, but mono-crystals were only observed in the sobol. Tannins, flavonoids, alkaloids, and terpenoids occurred in both types of bark, but carotenoids were only detected in the sobol. The similarities between these two organs indicate that the aerial stem bark has potential medicinal use and represents a plausible alternative to harvesting the sobol, which could contribute to the preservation of natural populations of this species.
The Query of Suitable Areas for plantation and development of Taxus baccata L Species by Using GIS in Northern Iran
Authors: ALAMI ANOSHIRVAN , ESLAMI ALIREZA , HASHEMI SEYED A.
Published: September 2014

Taxus baccata is a native species to the Caspian forests and is considered as the identification of these forests by some resources. The aim of this study was to understand the ecological characteristics of T. baccata in order to find suitable areas for its plantation in the Pone Aram preserve of Golestan province. Therefore, Multi-Criteria Evaluation (MCE) methods based on Analytical Hierarchy Process (AHP) were used. In this process at first the needed and effective natural indexes were used as 10 parameters. Then the final map of suitable areas for T. baccata plantation were produced based on Bolian and MCE models. According to the results, in Bolian method about 6218 ha of the total area of the study site (30554 ha) were estimated as suitable and semi suitable and 24336 ha were estimated as unsuitable for MCE model showed that about 2482 ha of the whole 30554 ha area of the study site is adequate for T. baccata plantation and 6181 ha is not adequate for T. baccata plantation. Regarding the results of the MCE and Bolian methods it has been concluded that for dynamic ecological parameters in delineation of suitable areas for T. baccata plantation the MCE weighting is more appropriate than Bolian. Using the results of this investigation it is possible to adequate areas for the presence of T. baccata and to execute a plan in order to facilitate the plantation of T. baccata in northern forests of Iran (watershed 88).
Influence of temperature and nutrient content on lipid production in freshwater microalgae cultures
Authors: BOHNENBERGER JULIANA E. , CROSSETTI LUCIANE O.
Published: September 2014

The production of biomass by microalgae is considered a clean alternative compared to other plant crops that require large areas for cultivation and that generate environmental impacts. This study evaluated the influence of temperature and nutrients on lipid contents of cultured species of freshwater microalgae, with a view toward using these lipids for biodiesel production. Two strains of Monoraphidium contortum, a culture containing Chlorella vulgaris and Desmodesmus quadricauda and another strain of Microcystis aeruginosa were maintained in the laboratory for six days, in five culture media: modified ASM-1 (control, with high concentrations of phosphate and nitrate; phosphorus-deficient; non-limiting phosphate; nitrogen-deficient; and non-limiting nitrate). The cultures were then exposed to temperatures of 13°C, 25°C (control) and 37°C for eight days (n=3). Lipids were extracted by the cold-solvent (methanol and chloroform) method. On average, the highest total lipid yields were observed when the strains were maintained at 13°C and in the non-limiting nitrate medium. The lipid percentage varied depending on the concentration of algal biomass. This study showed that manipulation of controlling factors can increase the lipid concentration, optimizing the total production in order to use this raw material for biodiesel.