bluuebunny/crossref_metadata_2025 huggingface dataset:
Air pollution research: visualization of research activity using density-equalizing mapping and scientometric benchmarking procedures
Authors: Zell Hanna , Quarcoo David , Scutaru Cristian , Vitzthum Karin , Uibel Stefanie , Schöffel Norman , Mache Stefanie , Groneberg David A , Spallek Michael F
Published: May 2010

Background

Due to constantly rising air pollution levels as well as an increasing awareness of the hazardousness of air pollutants, new laws and rules have recently been passed. Although there has been a large amount of research on this topic, bibliometric data is still to be collected. Thus this study provides a scientometric approach to the material published on this subject so far.

Methods

For this purpose, data retrieved from the "Web of Science" provided by the Thomson Scientific Institute was analyzed and visualized both with density-equalizing methods and classic data-processing methods such as tables and charts.

Results

For the time span between 1955 and 2006, 26,253 items were listed and related to the topic of air pollution, published by 124 countries in 24 different languages. General citation activity has been constantly increasing since the beginning of the examined period. However, beginning with the year 1991, citation levels have been rising exponentially each year, reaching 39,220 citations in the year 2006. The United States, the UK and Germany were the three most productive countries in the area, with English and German ranked first and second in publishing languages, followed by French. An article published by Dockery, Pope, Xu et al. was both the most cited in total numbers and in average citation rate. J. Schwartz was able to claim the highest total number of citations on his publications, while D.W. Dockery has the highest citation rate per publication. As to the subject areas the items are assigned with, the most item were published in Environmental Sciences, followed by Meteorology & Atmospheric Sciences and Public, Environmental & Occupational Health. Nine out of the ten publishing journals with more than 300 entries dealt with environmental interests and one dealt with epidemiology.

Conclusions

Using the method of density-equalizing mapping and further common data processing procedures, it can be concluded that scientific work concerning air pollution and related topics enjoys unbrokenly growing scientific interest. This can be observed both in publication numbers and in citation activity.
The likelihood of persistent arthritis increases with the level of anti-citrullinated peptide antibody and immunoglobulin M rheumatoid factor: a longitudinal study of 376 patients with very early undifferentiated arthritis
Authors: Mjaavatten Maria D , Heijde Désirée van der , Uhlig Till , Haugen Anne J , Nygaard Halvor , Sidenvall Göran , Helgetveit Knut , Kvien Tore K
Published: May 2010

Introduction

We wanted to assess the importance of the levels of anti-citrullinated peptide antibody (anti-CCP) and immunoglobulin M (IgM) rheumatoid factor (RF) in predicting development of persistent arthritis from undifferentiated arthritis (UA), and to investigate whether there is an added predictive value for persistent arthritis in testing for both anti-CCP and IgM RF.

Methods

Patients with UA (exclusion of definite non-rheumatoid arthritis (RA) diagnoses) included in the Norwegian very early arthritis clinic were assessed for development of persistent arthritic disease. The effect of antibody level on the likelihood of persistent arthritis was investigated, and the sensitivity and specificity for persistent arthritis for anti-CCP and IgM RF, separately and combined, was determined.

Results

A total of 376 UA patients were included (median arthritis duration 32 days). 59 (15.7%) patients were IgM RF positive, and 62 (16.5%) anti-CCP positive. One hundred, seventy-four (46.3%) had persistent disease after one year. Overlap of anti-CCP and IgM RF positivity was 58%. Sensitivity/specificity for persistent arthritis was 28/95% for IgM RF alone, 30/95% for anti-CCP alone, and 37/92% for positivity of both anti-CCP and IgM RF. The likelihood for persistent disease increased with increasing levels of both anti-CCP and IgM RF.

Conclusions

The likelihood of developing persistent arthritis in UA patients increases with the level of anti-CCP and IgM RF. Testing both anti-CCP and IgM RF has added predictive value in UA patients. This study suggests that antibody level should be taken into account when making risk assessments in patients with UA.
Endotoxemia-induced inflammation and the effect on the human brain
Authors: van den Boogaard Mark , Ramakers Bart P , van Alfen Nens , van der Werf Sieberen P , Fick Wilhelmina F , Hoedemaekers Cornelia W , Verbeek Marcel M , Schoonhoven Lisette , van der Hoeven Johannes G , Pickkers Peter
Published: May 2010

Introduction

Effects of systemic inflammation on cerebral function are not clear, as both inflammation-induced encephalopathy as well as stress-hormone mediated alertness have been described.

Methods

Experimental endotoxemia (2 ng/kg Escherichia coli lipopolysaccharide [LPS]) was induced in 15 subjects, whereas 10 served as controls. Cytokines (TNF-α, IL-6, IL1-RA and IL-10), cortisol, brain specific proteins (BSP), electroencephalography (EEG) and cognitive function tests (CFTs) were determined.

Results

Following LPS infusion, circulating pro- and anti-inflammatory cytokines, and cortisol increased (P < 0.0001). BSP changes stayed within the normal range, in which neuron specific enolase (NSE) and S100-β changed significantly. Except in one subject with a mild encephalopathic episode, without cognitive dysfunction, endotoxemia induced no clinically relevant EEG changes. Quantitative EEG analysis showed a higher state of alertness detected by changes in the central region, and peak frequency in the occipital region. Improved CFTs during endotoxemia was found to be due to a practice effect as CFTs improved to the same extent in the reference group. Cortisol significantly correlated with a higher state of alertness detected on the EEG. Increased IL-10 and the decreased NSE both correlated with improvement of working memory and with psychomotor speed capacity. No other significant correlations between cytokines, cortisol, EEG, CFT and BSP were found.

Conclusions

Short-term systemic inflammation does not provoke or explain the occurrence of septic encephalopathy, but primarily results in an inflammation-mediated increase in cortisol and alertness.

Trial registration

NCT00513110.
Simultaneous 3D depth-to-basement and density-contrast estimates using gravity data and depth control at few points
Authors: Martins Cristiano M. , Barbosa Valeria C. , Silva João B.
Published: May 2010

We have developed a gravity-inversion method for simultaneously estimating the 3D basement relief of a sedimentary basin and the parameters defining a presumed parabolic decay of the density contrast with depth in a sedimentary pack, assuming prior knowledge about the basement depth at a few points. The sedimentary pack is approximated by a grid of 3D vertical prisms juxtaposed in both horizontal directions of a right-handed coordinate system. The prisms’ thicknesses represent the depths to the basement and are the parameters to be estimated from the gravity data. To estimate the parameters defining the parabolic decay of the density contrast with depth and to produce stable depth-to-basement estimates, we imposed smoothness on the basement depths and proximity between estimated and known depths at boreholes. We applied our method to synthetic data from a simulated complex 3D basement relief with two sedimentary sections having distinct parabolic laws describing the density-contrast variation with depth. The results provide good estimates of the true parameters of the parabolic law of density-contrast decay with depth and of the basement relief. Inverting the gravity data from the onshore and part of the shallow offshore Almada Basin on Brazil’s northeastern coast shows good correlation with known structural features.
Fragile X mental retardation protein has a unique, evolutionarily conserved neuronal function not shared with FXR1P or FXR2P
Authors: Coffee R. Lane , Tessier Charles R. , Woodruff Elvin A. , Broadie Kendal
Published: May 2010

Fragile X syndrome (FXS), resulting solely from the loss of function of the human fragile X mental retardation 1 (hFMR1) gene, is the most common heritable cause of mental retardation and autism disorders, with syndromic defects also in non-neuronal tissues. In addition, the human genome encodes two closely related hFMR1 paralogs: hFXR1 and hFXR2. The Drosophila genome, by contrast, encodes a single dFMR1 gene with close sequence homology to all three human genes. Drosophila that lack the dFMR1 gene (dfmr1 null mutants) recapitulate FXS-associated molecular, cellular and behavioral phenotypes, suggesting that FMR1 function has been conserved, albeit with specific functions possibly sub-served by the expanded human gene family. To test evolutionary conservation, we used tissue-targeted transgenic expression of all three human genes in the Drosophila disease model to investigate function at (1) molecular, (2) neuronal and (3) non-neuronal levels. In neurons, dfmr1 null mutants exhibit elevated protein levels that alter the central brain and neuromuscular junction (NMJ) synaptic architecture, including an increase in synapse area, branching and bouton numbers. Importantly, hFMR1 can, comparably to dFMR1, fully rescue both the molecular and cellular defects in neurons, whereas hFXR1 and hFXR2 provide absolutely no rescue. For non-neuronal requirements, we assayed male fecundity and testes function. dfmr1 null mutants are effectively sterile owing to disruption of the 9+2 microtubule organization in the sperm tail. Importantly, all three human genes fully and equally rescue mutant fecundity and spermatogenesis defects. These results indicate that FMR1 gene function is evolutionarily conserved in neural mechanisms and cannot be compensated by either FXR1 or FXR2, but that all three proteins can substitute for each other in non-neuronal requirements. We conclude that FMR1 has a neural-specific function that is distinct from its paralogs, and that the unique FMR1 function is responsible for regulating neuronal protein expression and synaptic connectivity.
Adhesion molecules in the stem cell niche – more than just staying in shape?
Authors: Marthiens Véronique , Kazanis Ilias , Moss Lara , Long Katherine , ffrench-Constant Charles
Published: May 2010

The expression of adhesion molecules by stem cells within their niches is well described, but what is their function? A conventional view is that these adhesion molecules simply retain stem cells in the niche and thereby maintain its architecture and shape. Here, we review recent literature showing that this is but one of their roles, and that they have essential functions in all aspects of the stem cell-niche interaction – retention, division and exit. We also highlight from this literature evidence supporting a simple model whereby the regulation of centrosome positioning and spindle angle is regulated by both cadherins and integrins, and the differential activity of these two adhesion molecules enables the fundamental stem cell property of switching between asymmetrical and symmetrical divisions.
A mitotic kinesin-6, Pav-KLP, mediates interdependent cortical reorganization and spindle dynamics inDrosophilaembryos
Authors: Sommi Patrizia , Ananthakrishnan Revathi , Cheerambathur Dhanya K. , Kwon Mijung , Morales-Mulia Sandra , Brust-Mascher Ingrid , Mogilner Alex
Published: May 2010

We investigated the role of Pav-KLP, a kinesin-6, in the coordination of spindle and cortical dynamics during mitosis in Drosophila embryos. In vitro, Pav-KLP behaves as a dimer. In vivo, it localizes to mitotic spindles and furrows. Inhibition of Pav-KLP causes defects in both spindle dynamics and furrow ingression, as well as causing changes in the distribution of actin and vesicles. Thus, Pav-KLP stabilizes the spindle by crosslinking interpolar microtubule bundles and contributes to actin furrow formation possibly by transporting membrane vesicles, actin and/or actin regulatory molecules along astral microtubules. Modeling suggests that furrow ingression during cellularization depends on: (1) a Pav-KLP-dependent force driving an initial slow stage of ingression; and (2) the subsequent Pav-KLP-driven transport of actin- and membrane-containing vesicles to the furrow during a fast stage of ingression. We hypothesize that Pav-KLP is a multifunctional mitotic motor that contributes both to bundling of interpolar microtubules, thus stabilizing the spindle, and to a biphasic mechanism of furrow ingression by pulling down the furrow and transporting vesicles that deliver new material to the descending furrow.
Microvesicles: mediators of extracellular communication during cancer progression
Authors: Muralidharan-Chari Vandhana , Clancy James W. , Sedgwick Alanna , D'Souza-Schorey Crislyn
Published: May 2010

Microvesicles are generated by the outward budding and fission of membrane vesicles from the cell surface. Recent studies suggest that microvesicle shedding is a highly regulated process that occurs in a spectrum of cell types and, more frequently, in tumor cells. Microvesicles have been widely detected in various biological fluids including peripheral blood, urine and ascitic fluids, and their function and composition depend on the cells from which they originate. By facilitating the horizontal transfer of bioactive molecules such as proteins, RNAs and microRNAs, they are now thought to have vital roles in tumor invasion and metastases, inflammation, coagulation, and stem-cell renewal and expansion. This Commentary summarizes recent literature on the properties and biogenesis of microvesicles and their potential role in cancer progression.
Membrane wounding triggers ATP release and dysferlin-mediated intercellular calcium signaling
Authors: Covian-Nares J. Fernando , Koushik Srinagesh V. , Puhl Henry L. , Vogel Steven S.
Published: May 2010

Dysferlin is a Ca2+-binding protein found in many different cell types. It is required for membrane wound repair in muscle, but it is not known whether it has the same function in other cells. Here we report the activation of an intercellular signaling pathway in sea urchin embryos by membrane wounding that evokes Ca2+ spikes in neighboring cells. This pathway was mimicked by ATP application, and inhibited by apyrase, cadmium, and ω-agatoxin-IVA. Microinjection of dysferlin antisense phosphorodiamidate morpholino oligonucleotides blocked this pathway, whereas control morpholinos did not. Co-injection of mRNA encoding human dysferlin with the inhibitory morpholino rescued signaling activity. We conclude that in sea urchin embryos dysferlin mediates Ca2+-triggered intercellular signaling in response to membrane wounding.
Determination of Characteristic Wave Bands and Detection of Melamine in Fishmeal by Fourier Transform near Infrared Spectroscopy
Authors: Liu Xiaoli , Jia Gang , Wu Caimei , Wang Kangning , Wu Xiuqun
Published: May 2010

In China, fishmeal, which is of high value and nutritionally rich, is often a target for adulteration. Melamine, which is often one of the adulterants in fishmeal, will indirectly or directly cause hazards to human or animal health. In this study, Fourier near infrared spectroscopy (FT-NIR) was applied to achieve a rapid and cost-efficient classification and quantification technique for the authentification of fishmeal. The best model parameters and the characteristic wave bands of melamine were explored. The calibration models were established based on a principal components analysis (PCA)-Euclidean distance and partial least squares (PLS) regression algorithm. Five informative spectral bands (6828–6796 cm−1, 5022–4978 cm−1, 4776–4763 cm−1, 4637–4616 cm−1 and 4496–4481 cm−1) selected by the correlation coefficient method, were considered to be the characteristic wave bands of melamine. Savitzky-Golay (S–G) second derivative with smoothing over nine points and vector normalisation were the best pre-processing methods for a qualitative model; the 6873–6514 cm−1 region was selected to establish a qualitative model according to the spectra of a melamine standard and fishmeal, and the correct classification rate for a set of test samples was 99.5%. The best parameters were S-G first derivative with smoothing over nine points and multiplicative scatter correction pre-processing over the spectral regions of 9947–7394 cm−1 and 6915–5697 cm−1 for a wide range model (samples with melamine concentrations of 0–15%). S–G first derivative with smoothing over nine points and vector normalisation pre-processing over the spectral ranges of 9947–5697 cm−1 and 4605–4246 cm−1 were selected for a narrow range model (samples with melamine concentrations of 0–5.5%). The root mean square error of cross-validation of the wide range model and the narrow range model were 0.396% and 0.25%, respectively; the coefficients of determination ( R2) were 0.99 and 0.98; the root mean square error of prediction of testing set samples were 0.375% and 0.236%, respectively. The results demonstrate that FT-NIR can be used to detect and quantify melamine adulteration in fishmeal.
In-House Validation of a near Infrared Hyperspectral Imaging Method for Detecting Processed Animal Proteins in Compound Feed
Authors: Pierna Juan Antonio Fernandez , Dardenne Pierre , Baeten Vincent
Published: May 2010

This paper presents a framework for developing and validating a near infrared (NIR) hyperspectral imaging method as a standard protocol accepted by regulatory authorities. The focus is on detecting processed animal proteins (PAPs) in feedstuffs. Studies aimed at determining the performance characteristics and robustness of the protocol are presented. Various criteria and tests were used to assess the limit of detection, the repeatability and the risk of cross-contamination and to validate the NIR hyperspectral imaging method for detecting PAPs in compound feed. This protocol has been fully tested and validated though different studies in line with International Standard ISO 17025 and it is essential in order to transfer the method to other laboratories and introduce this technology to official control at the laboratory level.
Radial Variation in Cellulose Content and Kraft Pulp Yield in Eucalyptus Nitens using Near-Infrared Spectral Analysis of Air-Dry Wood Surfaces
Authors: Downes Geoffrey M. , Meder Roger , Ebdon Nicholas , Bond Helen , Evans Robert , Joyce Kelsey , Southerton Simon
Published: May 2010

To date, near infrared (NIR) spectroscopy calibrations to predict Kraft pulp yield (KPY) and cellulose content (CC) have been developed using wood meal samples. Our study, building upon such calibrations for KPY and CC, used NIR spectra collected at 5 mm intervals from the radial longitudinal surface of pith-to-bark breast height strips in 12 Eucalyptus nitens trees to develop calibrations for KPY and CC prediction from wood surface spectra. Both laboratory and portable NIR spectrometer instruments were effective in predicting radial variation, with standard errors of prediction in the vicinity of 1%. Both cellulose and KPY increased from pith to bark, showing a range of 5–8% within individual cores. The range was greater when the radial sampling interval was reduced to 1 mm, allowing the sub-annual variation to be better resolved. Commercially useful calibrations can now be developed quickly from air-dry increment cores and more cheaply than has been previously possible.
On-Line Fat Content Classification of Inhomogeneous Pork Trimmings Using Multispectral near Infrared Interactance Imaging
Authors: O'Farrell Marion , Wold Jens Petter , Høy Martin , Tschudi Jon , Schulerud Helene
Published: May 2010

A novel system for on-line measurement of fat content in inhomogeneous pork trimmings is presented. The system allows near infrared (NIR) energy to interact with the meat using non-contact optics while it is travelling in large plastic boxes on a conveyor belt. A comparison was made between the log of the inverse of the interactance NIR spectra [log(1/ T)], standard normal variate (SNV) and extended multiplicative signal correction (EMSC) as techniques for the correction of physical light scattering due to colour and textural differences, height variation and temperature fluctuations, depending on whether the meat was warm-cut or cold-cut. EMSC gave the best prediction results; a robust partial least squares regression using two factors resulted in a root mean square error ( RMSEP) of 1.9% on 20 kg batches of inhomogeneous meat trimmings. The model was fully tested twice in an on-line environment at a slaughter house and performed with a RMSEP of 3.4% for a fat range of 8–55% in the first industrial trial and 2.82% in the second industrial trial.
Calcium Activates a Chloride Conductance Likely Involved in Olfactory Receptor Neuron Repolarization in the MothSpodoptera littoralis
Authors: Pézier Adeline , Grauso Marta , Acquistapace Adrien , Monsempes Christelle , Rospars Jean-Pierre , Lucas Philippe
Published: May 2010

The response of insect olfactory receptor neurons (ORNs) to odorants involves the opening of Ca2+-permeable channels, generating an increase in intracellular Ca2+concentration. Here, we studied the downstream effect of this Ca2+rise in cultured ORNs of the mothSpodoptera littoralis. Intracellular dialysis of Ca2+from the patch pipette in whole-cell patch-clamp configuration activated a conductance with aK1/2of 2.8 μm. Intracellular and extracellular anionic and cationic substitutions demonstrated that Cl−carries this current. The anion permeability sequence I−> NO3−> Br−> Cl−> CH3SO3−≫ gluconate−of the Ca2+-activated Cl−channel suggests a weak electrical field pore of the channel. The Ca2+-activated current partly inactivated over time and did not depend on protein kinase C (PKC) and CaMKII activity or on calmodulin. Application of Cl−channel blockers, flufenamic acid, 5-nitro-2-(3-phenylpropylamino) benzoic acid, or niflumic acid reversibly blocked the Ca2+-activated current. In addition, lowering Cl−concentration in the sensillar lymph bathing the ORN outer dendrites caused a significant delay in pheromone response terminationin vivo. The present work identifies a new Cl−conductance activated by Ca2+in insect ORNs presumably required for ORN repolarization.
Gesture Discrimination in Primary Progressive Aphasia: The Intersection between Gesture and Language Processing Pathways
Authors: Nelissen Natalie , Pazzaglia Mariella , Vandenbulcke Mathieu , Sunaert Stefan , Fannes Katrien , Dupont Patrick , Aglioti Salvatore M. , Vandenberghe Rik
Published: May 2010

The issue of the relationship between language and gesture processing and the partial overlap of their neural representations is of fundamental importance to neurology, psychology, and social sciences. Patients suffering from primary progressive aphasia, a clinical syndrome characterized by comparatively isolated language deficits, may provide direct evidence for anatomical and functional association between specific language deficits and gesture discrimination deficits. A consecutive series of 16 patients with primary progressive aphasia and 16 matched control subjects participated. Our nonverbal gesture discrimination task consisted of 19 trials. In each trial, participants observed three video clips showing the same gesture performed correctly in one clip and incorrectly in the other two. Subjects had to indicate which of the three versions was correct. Language and gesture production were evaluated by means of conventional tasks. All participants underwent high-resolution structural and diffusion tensor magnetic resonance imaging. Ten of the primary progressive aphasia patients showed a significant deficit on the nonverbal gesture discrimination task. A factor analysis revealed that this deficit clustered with gesture imitation, word and pseudoword repetition, and writing-to-dictation. Individual scores on this cluster correlated with volume in the left anterior inferior parietal cortex extending into the posterior superior temporal gyrus. Probabilistic tractography indicated this region comprised the cortical relay station of the indirect pathway connecting the inferior frontal gyrus and the superior temporal cortex. Thus, the left perisylvian temporoparietal area may underpin verbal imitative behavior, gesture imitation, and gesture discrimination indicative of a partly shared neural substrate for language and gesture resonance.
Memory Impairment in Transgenic Alzheimer Mice Requires Cellular Prion Protein
Authors: Gimbel David A. , Nygaard Haakon B. , Coffey Erin E. , Gunther Erik C. , Laurén Juha , Gimbel Zachary A. , Strittmatter Stephen M.
Published: May 2010

Soluble oligomers of the amyloid-β (Aβ) peptide are thought to play a key role in the pathophysiology of Alzheimer's disease (AD). Recently, we reported that synthetic Aβ oligomers bind to cellular prion protein (PrPC) and that this interaction is required for suppression of synaptic plasticity in hippocampal slices by oligomeric Aβ peptide. We hypothesized that PrPCis essential for the ability of brain-derived Aβ to suppress cognitive function. Here, we crossed familial AD transgenes encoding APPswe and PSen1ΔE9 intoPrnp−/− mice to examine the necessity of PrPCfor AD-related phenotypes. Neither APP expression nor Aβ level is altered by PrPCabsence in this transgenic AD model, and astrogliosis is unchanged. However, deletion of PrPCexpression rescues 5-HT axonal degeneration, loss of synaptic markers, and early death in APPswe/PSen1ΔE9 transgenic mice. The AD transgenic mice with intact PrPCexpression exhibit deficits in spatial learning and memory. Mice lacking PrPC, but containing Aβ plaque derived from APPswe/PSen1ΔE9 transgenes, show no detectable impairment of spatial learning and memory. Thus, deletion of PrPCexpression dissociates Aβ accumulation from behavioral impairment in these AD mice, with the cognitive deficits selectively requiring PrPC.
Addictive Nicotine Alters Local Circuit Inhibition during the Induction ofIn VivoHippocampal Synaptic Potentiation
Authors: Zhang Tao A. , Tang Jianrong , Pidoplichko Volodymyr I. , Dani John A.
Published: May 2010

The drug addiction process shares many commonalities with normal learning and memory. Addictive drugs subvert normal synaptic plasticity mechanisms, and the consequent synaptic changes underlie long-lasting modifications in behavior that accrue during the progression from drug use to addiction. Supporting this hypothesis, it was recently shown that nicotine administered to freely moving mice induces long-term synaptic potentiation of the perforant path connection to granule cells of the dentate gyrus. The perforant path carries place and spatial information that links the environment to drug taking. An example of that association is the nicotine-induced synaptic potentiation of the perforant path that was found to underlie nicotine-conditioned place preference. The present study examines the influence of nicotine over local GABAergic inhibition within the dentate gyrus during the drug-induced synaptic potentiation.In vivorecordings from freely moving mice suggested that both feedforward and feedback inhibition onto granules cells were diminished by nicotine during the induction of synaptic potentiation.In vitrobrain slice studies indicated that nicotine altered local circuit inhibition within the dentate gyrus leading to disinhibition of granule cells. These changes in local inhibition contributed to nicotine-inducedin vivosynaptic potentiation, thus, likely contributed to drug-associated memories. Through this learning process, environmental features become cues that motivate conditioned drug-seeking and drug-taking behaviors.
Bone Morphogenetic Protein Signaling in the Developing Telencephalon Controls Formation of the Hippocampal Dentate Gyrus and Modifies Fear-Related Behavior
Authors: Caronia Giuliana , Wilcoxon Jennifer , Feldman Polina , Grove Elizabeth A.
Published: May 2010

The cortical hem is an embryonic signaling center that generates bone morphogenetic proteins (BMPs) and acts as an organizer for the hippocampus. The role of BMP signaling in hippocampal neurogenesis, however, has not been established. We therefore generated mice that were deficient inBmpr1bconstitutively, and deficient inBmpr1aconditionally in the dorsal telencephalon. In double mutant male and female mice, the dentate gyrus (DG) was dramatically smaller than in control mice, reflecting decreased production of granule neurons at the peak period of DG neurogenesis. Additionally, the pool of cells that generates new DG neurons throughout life was reduced, commensurate with the smaller size of the DG. Effects of diminished BMP signaling on the cortical hem were at least partly responsible for these defects in DG development. Reduction of the DG and its major extrinsic output to CA3 raised the possibility that the DG was functionally compromised. We therefore looked for behavioral deficits in double mutants and found that the mice were less responsive to fear- or anxiety-provoking stimuli, whether the association of the stimulus with fear or anxiety was learned or innate. Given that no anatomical defects appeared in the double mutant telencephalon outside the DG, our observations support a growing literature that implicates the hippocampus in circuitry mediating fear and anxiety. Our results additionally indicate a requirement for BMP signaling in generating the dorsalmost neuronal lineage of the telencephalon, DG granule neurons, and in the development of the stem cell niche that makes neurons in the adult hippocampus.
The Amiloride-Sensitive Epithelial Na+Channel PPK28 Is Essential forDrosophilaGustatory Water Reception
Authors: Chen Zijing , Wang Qingxiu , Wang Zuoren
Published: May 2010

Water sensation is a specific taste modality in the fruit fly. Water-induced hypoosmolarity activates specific gustatory receptor neurons; however, the molecular identity of the putative osmolarity sensor in these neurons remains unknown. We found that amiloride and its analogs specifically antagonized the response of water gustatory receptor neurons and the behavior of flies toward water stimulation. Deletion of the gene that encodes the amiloride-sensitive PPK28 channel, a DEG/eNaC (degenerin/epithelial sodium channel) family member, abolished the water-induced activity of water gustatory receptor neurons and greatly diminished the behavioral response of flies to water. Ectopic expression of the PPK28 channel in the bitter cells within the intermediate-type sensilla renders these sensilla responsive to water stimuli. Thus, the amiloride-sensitive PPK28 channel may serve as the osmolarity sensor for gustatory water reception in the fruit fly.
Peroxisome Proliferator-Activated Receptor δ Regulation of miR-15a in Ischemia-Induced Cerebral Vascular Endothelial Injury
Authors: Yin Ke-Jie , Deng Zhen , Hamblin Milton , Xiang Yi , Huang Huarong , Zhang Jifeng , Jiang Xiaodan , Wang Yanzhuang , Chen Y. Eugene
Published: May 2010

Cerebral vascular endothelial cell (CEC) degeneration significantly contributes to blood–brain barrier (BBB) breakdown and neuronal loss after cerebral ischemia. Recently, emerging data suggest that peroxisome proliferator-activated receptor δ (PPARδ) activation has a potential neuroprotective role in ischemic stroke. Here we report for the first time that PPARδ is significantly reduced in oxygen-glucose deprivation (OGD)-induced mouse CEC death. Interestingly, PPARδ overexpression can suppress OGD-induced caspase-3 activity, Golgi fragmentation, and CEC death through an increase of bcl-2 protein levels without change of bcl-2 mRNA levels. To explore the molecular mechanisms, we have identified that upregulation of PPARδ can alleviate ODG-activated microRNA-15a (miR-15a) expression in CECs. Moreover, we have demonstrated that bcl-2 is a translationally repressed target of miR-15a. Intriguingly, gain- or loss-of-miR-15a function can significantly reduce or increase OGD-induced CEC death, respectively. Furthermore, we have identified that miR-15a is a transcriptional target of PPARδ. Consistent with thein vitrofindings, we found that intracerebroventricular infusion of a specific PPARδ agonist, GW 501516 (2-[2-methyl-4-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methylsulfanyl]phenoxy]acetic acid), significantly reduced ischemia-induced miR-15a expression, increased bcl-2 protein levels, and attenuated caspase-3 activity and subsequent DNA fragmentation in isolated cerebral microvessels, leading to decreased BBB disruption and reduced cerebral infarction in mice after transient focal cerebral ischemia. Together, these results suggest that PPARδ plays a vascular-protective role in ischemia-like insults via transcriptional repression of miR-15a, resulting in subsequent release of its posttranscriptional inhibition of bcl-2. Thus, regulation of PPARδ-mediated miR-15a inhibition of bcl-2 could provide a novel therapeutic strategy for the treatment of stroke-related vascular dysfunction.
Axonal Degeneration Is Regulated by the Apoptotic Machinery or a NAD+-Sensitive Pathway in Insects and Mammals
Authors: Schoenmann Zohar , Assa-Kunik Efrat , Tiomny Sheila , Minis Adi , Haklai-Topper Liat , Arama Eli , Yaron Avraham
Published: May 2010

Selective degeneration of neuronal projections and neurite pruning are critical for establishment and maintenance of functional neural circuits in both insects and mammals. However, the molecular mechanisms that govern developmental neurite pruning versus injury-induced neurite degeneration are still mostly unclear. Here, we show that the effector caspases 6 and 3 are both expressed within axons and that, on trophic deprivation, they exhibit distinct modes of activation. Surprisingly, inhibition of caspases is not sufficient for axonal protection and a parallel modulation of a NAD+-sensitive pathway is required. The proapoptotic protein BAX is a key element in both pathways as its genetic ablation protected sensory axons against developmental degeneration bothin vitroandin vivo. Last, we demonstrate that both pathways are also involved in developmental dendritic pruning inDrosophila. More specifically, the mouse WldS(Wallerian degeneration slow) protein, which is mainly composed of the full-length sequence of the NAD+biosynthetic Nmnat1 enzyme, can suppress dendritic pruning in C4da (class IV dendritic arborization) sensory neurons in parallel to the fly effector caspases. These findings indicate that two distinct autodestruction pathways act separately or in concert to regulate developmental neurite pruning.
Alterations in the Hippocampal Endocannabinoid System in Diet-Induced Obese Mice
Authors: Massa Federico , Mancini Giacomo , Schmidt Helmut , Steindel Frauke , Mackie Ken , Angioni Carlo , Oliet Stéphane H. R. , Geisslinger Gerd , Lutz Beat
Published: May 2010

The endocannabinoid (eCB) system plays central roles in the regulation of food intake and energy expenditure. Its alteration in activity contributes to the development and maintenance of obesity. Stimulation of the cannabinoid receptor type 1 (CB1receptor) increases feeding, enhances reward aspects of eating, and promotes lipogenesis, whereas its blockade decreases appetite, sustains weight loss, increases insulin sensitivity, and alleviates dysregulation of lipid metabolism. The hypothesis has been put forward that the eCB system is overactive in obesity. Hippocampal circuits are not directly involved in the neuronal control of food intake and appetite, but they play important roles in hedonic aspects of eating. We investigated the possibility whether or not diet-induced obesity (DIO) alters the functioning of the hippocampal eCB system. We found that levels of the two eCBs, 2-arachidonoyl glycerol (2-AG) and anandamide, were increased in the hippocampus from DIO mice, with a concomitant increase of the 2-AG synthesizing enzyme diacylglycerol lipase-α and increased CB1receptor immunoreactivity in CA1 and CA3 regions, whereas CB1receptor agonist-induced [35S]GTPγS binding was unchanged. eCB-mediated synaptic plasticity was changed in the CA1 region, as depolarization-induced suppression of inhibition and long-term depression of inhibitory synapses were enhanced. Functionality of CB1receptors in GABAergic neurons was furthermore revealed, as mice specifically lacking CB1receptors on this neuronal population were partly resistant to DIO. Our results show that DIO-induced changes in the eCB system affect not only tissues directly involved in the metabolic regulation but also brain regions mediating hedonic aspects of eating and influencing cognitive processes.
Multiple Kinase Pathways Regulate Voltage-Dependent Ca2+Influx and Migration in Oligodendrocyte Precursor Cells
Authors: Paez Pablo M. , Fulton Daniel J. , Spreur Vilma , Handley Vance , Campagnoni Anthony T.
Published: May 2010

It is becoming increasingly clear that voltage-operated Ca2+channels (VOCCs) play a fundamental role in the development of oligodendrocyte progenitor cells (OPCs). Because direct phosphorylation by different kinases is one of the most important mechanisms involved in VOCC modulation, the aim of this study was to evaluate the participation of serine–threonine kinases and tyrosine kinases (TKs) on Ca2+influx mediated by VOCCs in OPCs. Calcium imaging revealed that OPCs exhibited Ca2+influx after plasma membrane depolarization via L-type VOCCs. Furthermore, VOCC-mediated Ca2+influx declined with OPC differentiation, indicating that VOCCs are developmentally regulated in OPCs. PKC activation significantly increased VOCC activity in OPCs, whereas PKA activation produced the opposite effect. The results also indicated that OPC morphological changes induced by PKC activation were partially mediated by VOCCs. Our data clearly suggest that TKs exert an activating influence on VOCC function in OPCs. Furthermore, using the PDGF response as a model to probe the role of TK receptors (TKr) on OPC Ca2+uptake, we found that TKr activation potentiated Ca2+influx after membrane depolarization. Interestingly, this TKr modulation of VOCCs appeared to be essential for the PDGF enhancement of OPC migration rate, because cell motility was completely blocked by TKr antagonists, as well as VOCC inhibitors, in migration assays. The present study strongly demonstrates that PKC and TKrs enhance Ca2+influx induced by depolarization in OPCs, whereas PKA has an inhibitory effect. These kinases modulate voltage-operated Ca2+uptake in OPCs and participate in the modulation of process extension and migration.
Noninvasive Imaging of Endogenous Neural Stem Cell MobilizationIn VivoUsing Positron Emission Tomography
Authors: Rueger Maria Adele , Backes Heiko , Walberer Maureen , Neumaier Bernd , Ullrich Roland , Simard Marie-Lune , Emig Beata , Fink Gereon Rudolf , Hoehn Mathias , Graf Rudolf , Schroeter Michael
Published: May 2010

Neural stem cells reside in two major niches in the adult brain [i.e., the subventricular zone (SVZ) and the dentate gyrus of the hippocampus]. Insults to the brain such as cerebral ischemia result in a physiological mobilization of endogenous neural stem cells. Since recent studies showed that pharmacological stimulation can be used to expand the endogenous neural stem cell niche, hope has been raised to enhance the brain's own regenerative capacity. For the evaluation of such novel therapeutic approaches, longitudinal and intraindividual monitoring of the endogenous neural stem cell niche would be required. However, to date no conclusive imaging technique has been established. We used positron emission tomography (PET) and the radiotracer 3′-deoxy-3′-[18F]fluoro-l-thymidine ([18F]FLT) that enables imaging and measuring of proliferation to noninvasively detect endogenous neural stem cells in the normal and diseased adult rat brainin vivo. This method indeed visualized neural stem cell niches in the living rat brain, identified as increased [18F]FLT-binding in the SVZ and the hippocampus. Focal cerebral ischemia and subsequent damage of the blood–brain barrier did not interfere with the capability of [18F]FLT-PET to visualize neural stem cell mobilization. Moreover, [18F]FLT-PET allowed for anin vivoquantification of increased neural stem cell mobilization caused by pharmacological stimulation or by focal cerebral ischemia. The data suggest that noninvasive longitudinal monitoring and quantification of endogenous neural stem cell activation in the brain is feasible and that [18F]FLT-PET could be used to monitor the effects of drugs aimed at expanding the neural stem cell niche.
Methylation Regulates Alpha-Synuclein Expression and Is Decreased in Parkinson's Disease Patients' Brains
Authors: Jowaed Ahmad , Schmitt Ina , Kaut Oliver , Wüllner Ullrich
Published: May 2010

Alpha-synuclein (SNCA) is a major risk gene for Parkinson's disease (PD), and increasedSNCAgene dosage results in a parkinsonian syndrome in affected families. We found that methylation of humanSNCAintron 1 decreased gene expression, while inhibition of DNA methylation activated SNCA expression. Methylation ofSNCAintron 1 was reduced in DNA from sporadic PD patients' substantia nigra, putamen, and cortex, pointing toward a yet unappreciated epigenetic regulation ofSNCAexpression in PD.
PICK1 Regulates Incorporation of Calcium-Permeable AMPA Receptors during Cortical Synaptic Strengthening
Authors: Clem Roger L. , Anggono Victor , Huganir Richard L.
Published: May 2010

While AMPA-type glutamate receptors (AMPARs) found at principal neuron excitatory synapses typically contain the GluR2 subunit, several forms of behavioral experience have been linked to thede novosynaptic insertion of calcium-permeable (CP) AMPARs, defined by their lack of GluR2. In particular, whisker experience drives synaptic potentiation as well as the incorporation of CP-AMPARs in the neocortex. Previous studies implicate PICK1 (protein interacting with C kinase-1) in activity-dependent internalization of GluR2, suggesting one potential mechanism leading to the subsequent accumulation of synaptic CP-AMPARs and increased synaptic strength. Here we test this hypothesis by using a whisker stimulation paradigm in PICK1 knock-out mice. We demonstrate that PICK1 facilitates the surface expression of CP-AMPARs and is indispensable for their experience-dependent synaptic insertion. However, the failure to incorporate CP-AMPARs in PICK1 knock-outs does not preclude sensory-induced enhancement of synaptic currents. Our results indicate that synaptic strengthening in the early postnatal cortex does not require PICK1 or the addition of GluR2-lacking AMPARs. Instead, PICK1 permits changes in AMPAR subunit composition to occur in conjunction with synaptic potentiation.
The psychological factors affecting athletic performance
Authors: Resch Mária
Published: May 2010

A XXI. század vívmányaként hangoztatják a testi-lelki egészség komplexet, amelynek részeként a sportolók körében is mind nagyobb figyelmet szánnak a szomatikus orvoslás mellett a pszichére is. A sportpszichiátriát húzták elő és állították a teljesítményfokozás szolgálatába akkor is, amikor már valamennyi biológiai fegyvert elpuffogtattak, s a várva várt eredmény még mindig nem jött meg. Sőt, egyre több energiaráfordítás ellenére egyre rosszabbá vált. A sportolók körében több pszichiátriai kórkép hívja fel magára a figyelmet vagy a magas prevalencia, vagy egy-egy specifikus szindróma kialakulása által. A depresszió (versenyzés utáni depresszió, a megmérettetés meghiúsulása utáni depresszió), a krónikus stressz, szorongás, a túledzési szindróma, fáradékonyság, enerváltság, alvászavarok, étkezési zavarok tünetei, a burnout, az evészavarok (anorexia athletica, atlétatriász), személyiségtényezők és a kémiai addikciók mind rendkívül fontosak. A jelen tanulmány elsőként foglalja össze azokat a legfontosabb pszichiátriai kórképeket, amelyek a sportolópopulációban, az egyes sportágak szerint különböző mértékben, nagy jelentőséggel bírhatnak.
Brain SPECT in mesial temporal lobe epilepsy: comparison between visual analysis and SPM
Authors: Amorim Bárbara Juarez , Ramos Celso Darío , Santos Allan Oliveira dos , Lima Mariana da Cunha Lopes de , Min Li Li , Camargo Edwaldo Eduardo , Cendes Fernando , Etchebehere Elba Cristina Sá de Camargo
Published: May 2010

OBJECTIVE: To compare the accuracy of SPM and visual analysis of brain SPECT in patients with mesial temporal lobe epilepsy (MTLE). METHOD: Interictal and ictal SPECTs of 22 patients with MTLE were performed. Visual analysis were performed in interictal (VISUAL(inter)) and ictal (VISUAL(ictal/inter)) studies. SPM analysis consisted of comparing interictal (SPM(inter)) and ictal SPECTs (SPM(ictal)) of each patient to control group and by comparing perfusion of temporal lobes in ictal and interictal studies among themselves (SPM(ictal/inter)). RESULTS: For detection of the epileptogenic focus, the sensitivities were as follows: VISUAL(inter)=68%; VISUAL(ictal/inter)=100%; SPM(inter)=45%; SPM(ictal)=64% and SPM(ictal/inter)=77%. SPM was able to detect more areas of hyperperfusion and hypoperfusion. CONCLUSION: SPM did not improve the sensitivity to detect epileptogenic focus. However, SPM detected different regions of hypoperfusion and hyperperfusion and is therefore a helpful tool for better understand pathophysiology of seizures in MTLE.
Emergency EEG: study of survival
Authors: Borges Moacir Alves , Botós Harethusa Junia , Bastos Ricardo Funes , Godoy Moacir Fernandes , Marchi Nely Silvia Aragão de
Published: May 2010

OBJECTIVE: To determine the survival rate according to the main findings of emergency electroencephalography (EEGs) of patients treated in a tertiary hospital. METHOD: In this prospective study, the findings of consecutive emergency EEGs performed on inpatients in Hospital de Base in São José do Rio Preto, Brazil were correlated with survival utilizing Kaplan-Meyer survival curves. RESULTS: A total of 681 patients with an average age of 42 years old (1 day to 96 years) were evaluated, of which 406 were male. The main reasons for EEGs were epileptic seizures (221 cases), hepatic encephalopathy [116 cases of which 85 (73.3%) were men, p-value=0.001], status epilepticus (104 cases) and impaired consciousness (78 cases). The underlying disease was confirmed in 578 (84.3%) cases with 119 (17.5%) having liver disease [91 (76.0%) were men, p-value=0.001], 105 (15.4%) suffering strokes, 67 (9.9%) having metabolic disorders, 51 (7.5%) central nervous system infections and 49 (7.2%) epilepsy. In the three months following EEG, a survival rate of 75% was found in patients with normal, discreet slow activity or intermittent rhythmic delta activity EEGs, of 50% for those with continuous delta activity and generalized epileptiform discharges, and of 25% for those with burst-suppression, diffuse depression, and in alpha/theta-pattern coma. Death was pronounced immediately in patients with isoelectric EEGs. CONCLUSION: The main findings of EEGs, differentiated different survival rates and are thus a good prognostic tool for patients examined in emergencies.
Psychological assessment in patients with phobic postural vertigo
Authors: Ferreira Liliani Souza dos Santos , Pereira Cristiana Borges , Rossini Sueli , Kanashiro Aline Mizuta Kozoroski , Adda Carla Cristina , Scaff Milberto
Published: May 2010

Phobic postural vertigo (PPV) is a frequent diagnosis which can be challenging to treat. OBJECTIVE: To investigate the presence of psychiatric disturbances in patients with PPV; to assess the psychological status of patients using adaptive diagnosis; to verify possible correlations between severity of psychiatric disturbance and adaptive efficacy. METHOD: A total of nineteen subjects were assessed and two instruments applied: the Primary Care Evaluation of Mental Disorders Questionnaire (PRIME-MD) and the Adaptive Operationalized Diagnostic Scale (AODS), and results from both tests were compared. RESULTS: Fourteen patients presented with mood disorder and thirteen with anxiety. All patients presented compromised adaptive efficacy. Correlation was found between overall outcome on the PRIME and the AODS (tau= -0.42, p=0.027), Separate analysis revealed correlation between results of the AODS and anxiety disorders (tau= -0.45, p=0.018) but not with mood disorders (tau= -0.36, p=0.054). CONCLUSION: Adaptive compromise was observed in individuals with PPV which was shown to be associated to psychiatric disorders.