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Selected AbstractsDeep brain stimulation mechanisms: beyond the concept of local functional inhibitionEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2010Jean-Michel Deniau Abstract Deep brain electrical stimulation has become a recognized therapy in the treatment of a variety of motor disorders and has potentially promising applications in a wide range of neurological diseases including neuropsychiatry. Behavioural observation that electrical high-frequency stimulation of a given brain area induces an effect similar to a lesion suggested a mechanism of functional inhibition. In vitro and in vivo experiments as well as per operative recordings in patients have revealed a variety of effects involving local changes of neuronal excitability as well as widespread effects throughout the connected network resulting from activation of axons, including antidromic activation. Here we review current data regarding the local and network activity changes induced by high-frequency stimulation of the subthalamic nucleus and discuss this in the context of motor restoration in Parkinson's disease. Stressing the important functional consequences of axonal activation in deep brain stimulation mechanisms, we highlight the importance of developing anatomical knowledge concerning the fibre connections of the putative therapeutic targets. [source] The Indochinese,Sundaic zoogeographic transition: a description and analysis of terrestrial mammal species distributionsJOURNAL OF BIOGEOGRAPHY, Issue 5 2009David S. Woodruff Abstract Aim, We describe the distributions of mammal species between the Indochinese and Sundaic subregions and examine the traditional view that the two faunas show a transition near the Isthmus of Kra on the Thai,Malay peninsula. Location, Species distributions are described along a 2000-km transect from 20° N (northernmost Thailand) to 1° N (Singapore). Methods, For the 325 species of native non-marine mammals occurring along the transect we used published records to provide a database of their distributional records by degree of latitude. Results, Along the transect we found 128 Indochinese species with southern range limits, 121 Sundaic species with northern range limits, four un-assignable endemics and 72 widespread species. In total, 152 southern and 147 northern range limits were identified, and their distribution provides no evidence for a narrow faunal transition near the Isthmus of Kra (10°30, N) or elsewhere. Range limits of both bats and non-volant mammals cluster in northernmost peninsular Malaysia (5° N) and 800 km further north, where the peninsula joins the continent proper (14° N). The clusters of northern and southern range limits are not concordant but overlap by 100,200 km. Similarly, the range limits of bats and non-volant mammals cluster at slightly different latitudes. There are 30% fewer species and range limits in the central and northern peninsula (between 6 and 13° N), and 35 more widely distributed species have range gaps in this region. In addition, we found 70 fewer species at the southern tip of the peninsula (1° N) than at 3,4° N. Main conclusions, The deficiencies of both species and species range limits in the central and northern peninsula are attributed to an area effect caused by repeated sea-level changes. Using a new global glacioeustatic curve developed by Miller and associates we show that there were > 58 rapid sea-level rises of > 40 m in the last 5 Myr that would have resulted in significant faunal compression and local population extirpation in the narrow central and northern parts of the peninsula. This new global sea-level curve appears to account for the observed patterns of the latitudinal diversity of mammal species, the concentration of species range limits north and south of this area, the nature and position of the transition between biogeographical subregions, and possibly the divergence of the faunas themselves during the Neogene. The decline of species diversity at the southern end of the transect is attributed to a peninsula effect similar to that described elsewhere. [source] Calcium control of gene regulation in rat hippocampal neuronal culturesJOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2009Giulietta Pinato Blockage of GABA-A receptors in hippocampal neuronal cultures triggers synchronous bursts of spikes initiating neuronal plasticity, partly mediated by changes of gene expression. By using specific pharmacological blockers, we have investigated which sources of Ca2+ entry primarily control changes of gene expression induced by 20,µM gabazine applied for 30,min (GabT). Intracellular Ca2+ transients were monitored with Ca2+ imaging while recording electrical activity with patch clamp microelectrodes. Concomitant transcription profiles were obtained using Affymetrix oligonucleotide microarrays and confirmed with quantitative RT-PCR. Blockage of NMDA receptors with 2-amino-5-phosphonovaleric acid (APV) did not reduce significantly somatic Ca2+ transients, which, on the contrary, were reduced by selective blockage of L, N, and P/Q types voltage gated calcium channels (VGCCs). Therefore, we investigated changes of gene expression in the presence of blockers of NMDA receptors and L, N, and P/Q VGCCs. Our results show that: (i) among genes upregulated by GabT, there are genes selectively dependent on NMDA activation, genes selectively dependent on L-type VGCCs and genes dependent on the activation of both channels; (ii) the majority of genes requires the concomitant activation of NMDA receptors and Ca2+ entry through VGCCs; (iii) blockage of N and P/Q VGCCs has an effect similar but not identical to blockage of L-type VGCCs. J. Cell. Physiol. 220: 727,747, 2009. © 2009 Wiley-Liss, Inc. [source] Role of Internal Friction in Indentation Damage in a Mica-Containing Glass-CeramicJOURNAL OF THE AMERICAN CERAMIC SOCIETY, Issue 11 2001Anthony C. Fischer-Cripps The indentation response of a mica-containing glass-ceramic that exhibits shear-driven yield in an indentation test is interpreted in terms of events occurring on the microstructural scale. It is proposed that shear-driven damage within the specimen occurs via internal sliding along cleavage planes within the mica platelets. The sliding surfaces in this case are considered to be atomically smooth so the real and apparent areas of contact coincide. The frictional shear stress is thus independent of the normal forces arising from thermal mismatch stresses and only depends on the work of adhesion of the interface and the scale of the contacts. The scale of contacts for these materials lies within an intermediate zone in which the frictional shear stress arises from the stress required to nucleate dislocation-like discontinuities within the material. This leads to a size effect similar to that experienced by a crack in Mode II loading and is in accordance with previous work in which a connection between such a size effect and the macroscopic response of the material was identified. This work has particular relevance to the design and manufacturing of ceramics in machining, wear, bearings, and coatings applications. [source] On the properties of the periodogram of a stationary long-memory process over different epochs with applicationsJOURNAL OF TIME SERIES ANALYSIS, Issue 1 2010Valdério A. Reisen Primary 60G10; 60K35; Secondary 60G18 This article studies the asymptotic properties of the discrete Fourier transforms (DFT) and the periodogram of a stationary long-memory time series over different epochs. The main theoretical result is a novel bound for the covariance of the DFT ordinates evaluated on two distinct epochs, which depends explicitly on the Fourier frequencies and the gap between the epochs. This result is then applied to obtain the limiting distribution of some nonlinear functions of the periodogram over different epochs, under the additional assumption of gaussianity. We then apply this result to construct an estimator of the memory parameter based on the regression in a neighbourhood of the zero-frequency of the logarithm of the averaged periodogram, obtained by computing the empirical mean of the periodogram over adjacent epochs. It is shown that replacing the periodogram by its average has an effect similar to the frequency domain pooling to reduce the variance of the estimate. We also propose a simple procedure to test the stationarity of the memory coefficient. A limited Monte Carlo experiment is presented to support our findings. [source] Electron beam,specimen interactions and their effect on high-angle annular dark-field imaging of dopant atoms within a crystalACTA CRYSTALLOGRAPHICA SECTION A, Issue 3 2010B. G. Mendis A Bloch wave model based on perturbation theory is used to analyse high-angle annular dark-field (HAADF) imaging of a substitutional and interstitial W atom in [111]-oriented body-centred-cubic Fe. For the substitutional atom the 1s Bloch state is scattered to high angles thereby producing HAADF dopant atom contrast. Intraband scattering of the 1s state is the strongest individual Bloch wave transition but collective interband scattering of the non-1s states to the 1s state leads to variations in the high-angle scattering with depth of the dopant atom. The non-1s states are Coulomb attracted towards the W atom thereby giving rise to an `atom focusing' effect similar to channelling. For the interstitial atom, which in the [111] orientation does not overlap with an atom column of the host lattice, high-angle scattering and Coulomb attraction takes place through the non-1s states. Scattering of the 1s state is, however, negligible. [source] Allelic variation of a BalI polymorphism in the DRD3 gene does not influence susceptibility to bipolar disorder: Results of analysis and meta-analysisAMERICAN JOURNAL OF MEDICAL GENETICS, Issue 4 2001Gareth Elvidge Abstract Bipolar disorder is a major psychiatric illness that has evidence for a significant genetic contribution toward its development. In recent years, the BalI RFLP (restriction fragment length polymorphism) in the dopamine D3 receptor gene has been examined as a possible susceptibility factor for both schizophrenia and bipolar disorder. While analysis in schizophrenia has produced examples of increased homozygosity in patients, less encouraging results have been found for bipolar disorder. Recently, however, a family-based association study has found a significant excess of allele 1 and allele 1,containing genotypes in transmitted alleles to bipolar probands over nontransmitted controls. In a large bipolar case control sample (n,=,454), we have been unable to replicate the family-based association study (chi-square,=,0.137, P,=,0.71, 1 df) or detect an effect similar to the positive homozygosity findings in schizophrenia (chi-square,=,0.463, P,=,0.50, 1 df). A meta-analysis of previous association studies also revealed no difference in allele distributions between bipolar patients and controls for this polymorphism in ethnically homogeneous samples (odds ratio, OR,,=,1.04; P,=,0.60; 95% confidence interval, CI,,=,0.89,1.20). In view of this evidence, we conclude that variation at the BalI RFLP is not an important factor influencing the susceptibility to bipolar disorder. It remains possible, however, that other sequence variations within the DRD3 gene could play a role. © 2001 Wiley-Liss, Inc. [source] Survival during a Crisis: Alliances by Singapore FirmsBRITISH JOURNAL OF MANAGEMENT, Issue 3 2007Nitin Pangarkar In this study, we focus on the under-researched issue of how environmental shocks impact alliance survival. We draw from several different theoretical perspectives such as industrial organization economics, managerial theories of the firm (such as agency theory) and institutional theories. We argue that the relationship between the occurrence of environmental shock and alliance survival is a contingent one. Specifically, we hypothesize that the following types of alliances will exhibit better likelihood of survival: alliances that yield a balance of short-term and long-term benefits (scale alliances) rather than purely long-term benefits (link alliances); alliances that lead to either cost reduction or near-term improvement in revenue realization (marketing alliances); and alliances that bring together partners from different economic regions (those involving Western and Asian partners). Based on an analysis of 348 alliances formed by Singapore firms, we find that marketing alliances and those involving at least one Western partner indeed exhibit a better likelihood of survival during the Asian economic crisis. We conclude that alliances that can enhance revenue potential in the short-term are more robust to environmental shocks and that alliances can benefit from an effect similar to risk reduction through international diversification. [source] How Post-Translational Modifications Influence Amyloid Formation: A Systematic Study of Phosphorylation and Glycosylation in Model PeptidesCHEMISTRY - A EUROPEAN JOURNAL, Issue 26 2010Malgorzata Broncel Abstract A reciprocal relationship between phosphorylation and O-glycosylation has been reported for many cellular processes and human diseases. The accumulated evidence points to the significant role these post-translational modifications play in aggregation and fibril formation. Simplified peptide model systems provide a means for investigating the molecular changes associated with protein aggregation. In this study, by using an amyloid-forming model peptide, we show that phosphorylation and glycosylation can affect folding and aggregation kinetics differently. Incorporation of phosphoserines, regardless of their quantity and position, turned out to be most efficient in preventing amyloid formation, whereas O-glycosylation has a more subtle effect. The introduction of a single ,-galactose does not change the folding behavior of the model peptide, but does alter the aggregation kinetics in a site-specific manner. The presence of multiple galactose residues has an effect similar to that of phosphorylation. [source] Correlation between R/S enantiomer ratio of lansoprazole and CYP2C19 activity after single oral and enteral administrationCHIRALITY, Issue 7 2010Masatomo Miura Abstract The purpose of this study was to investigate whether CYP2C19 activity can be estimated from plasma concentrations of lansoprazole enantiomers 4 h (C4h) after single administration by oral and enteral routes. Sixty-nine subjects, 22 homozygous extensive metabolizers (homEMs), 32 heterozygous EMs (hetEMs), and 15 poor metabolizers (PMs), participated in the study. After a single oral or enteral dose of racemic lansoprazole (30 mg), plasma concentrations of lansoprazole enantiomers were measured 4 h postdose. The R/S ratio of lansoprazole at 4 h differed significantly among the three groups (P < 0.0001) regardless of the administration route. The R/S ratio of lansoprazole in CYP2C19 PMs ranged from 3.0 to 13.7, whereas in homEMs and hetEMs the ratio ranged from 8.6 to 90 and 2.1 to 122, respectively. The relationship between (S)-lansoprazole concentration and R/S ratio of lansoprazole at C4h is given by the following formula: log10 [R/S ratio] = 2.2 , 0.64 × log10 [C4h of (S)-lansoprazole] (r = 0.867, P < 0.0001). Thus, phenotyping CYP2C19 using the R/S enantiomer ratio of lansoprazole seems unlikely. However, to obtain a pharmacological effect similar to that in CYP2C19 PMs, we can presume that lansoprazole has a sufficient effect in the patient with an R/S enantiomer ratio at 4 h , 13.70 and (S)-lansoprazole concentration at 4 h , 50 ng/ml. Chirality 2010. © 2009 Wiley-Liss, Inc. [source] | |||||||||||||