Geranylgeranyltransferase I is essential for dendritic development of cerebellar Purkinje cells

<p>Abstract</p> <p>Background</p> <p>During cerebellar development, Purkinje cells (PCs) form the most elaborate dendritic trees among neurons in the brain, but the mechanism regulating PC arborization remains largely unknown. Geranylgeranyltransferase I (GGT) is a prenyltransferase that is responsible for lipid modification of several signaling proteins, such as Rho family small GTPase Rac1, which has been shown to be involved in neuronal morphogenesis. Here we show that GGT plays an important role in dendritic development of PCs.</p> <p>Results</p> <p>We found that GGT was abundantly expressed in the developing rat cerebellum, in particular molecular layer (ML), the region enriched with PC dendrites. Inhibition or down-regulation of GGT using small interference RNA (siRNA) inhibited dendritic development of PCs. In contrast, up-regulation of GGT promoted dendritic arborization of PCs. Furthermore, neuronal depolarization induced by high K⁺or treatment with brain-derived neurotrophic factor (BDNF) promoted membrane association of Rac1 and dendritic development of PCs in cultured cerebellar slices. The effect of BDNF or high K⁺was inhibited by inhibition or down-regulation of GGT.</p> <p>Conclusion</p> <p>Our results indicate that GGT plays an important role in Purkinje cell development, and suggest a novel role of GGT in neuronal morphogenesis <it>in vivo</it>.</p

Expression pattern and activity of six glutelin gene promoters in transgenic rice*

The shortage of strong endosperm-specific expression promoters for driving the expression of recombinant protein genes in cereal endosperm is a major limitation in obtaining the required level and pattern of expression. Six promoters of seed storage glutelin genes (GluA-1, GluA-2, GluA-3, GluB-3, GluB-5, and GluC) were isolated from rice (Oryza sativa L.) genomic DNA by PCR. Their spatial and temporal expression patterns and expression potential in stable transgenic rice plants were examined with β-glucuronidase (GUS) used as a reporter gene. All the promoters showed the expected spatial expression within the endosperm. The GluA-1, GluA-2, and GluA-3 promoters directed GUS expression mainly in the outer portion (peripheral region) of the endosperm. The GluB-5 and GluC promoters directed GUS expression in the whole endosperm, with the latter expressed almost evenly throughout the whole endosperm, a feature different from that of other rice glutelin gene promoters. The GluB-3 promoter directed GUS expression solely in aleurone and subaleurone layers. Promoter activities examined during seed maturation showed that the GluC promoter had much higher activity than the other promoters. These promoters are ideal candidates for achieving gene expression for multiple purposes in monocot endosperm but avoid promoter homology-based gene silencing. The GluC promoter did not contain the endosperm specificity-determining motifs GCN4, AACA, and the prolamin-box, which suggests the existence of additional regulatory mechanism in determining endosperm specificity

Molecular docking studies on rocaglamide, a traditional Chinese medicine for periodontitis

Purpose: To undertake an in silico assessment of rocaglamide as a potential drug therapy forperiodontitis (dental arthritis).Method: Lamarckian algorithm-based automated docking approach using AutoDock4.2 tool wasapplied for calculating the best possible binding mode of rocaglamide to IL-23p19 and IL-17, the targets of anti-inflammatory drugs in periodontal disease.Results: The top two interactions of rocaglamide with IL-17 (ΔG = -5.45 and -4.83 kcal/mol) were more spontaneous, and the physical interactions (two hydrogen bonds and one π-πbond) generated in the two IL-17- rocaglamide complexes were higher in number than in IL-23p14-rocaglamide complexes.Conclusion: In silico analysis of rocaglamide, a known antimicrobial and anti-inflammatory agent, is a promising natural candidate for periodontitis therapy, and should be further subjected to in vitro and in vivo anti-periodontitis investigations.Keywords: Periodontitis, Inflammation, Rocaglamide, Molecular docking, Lamarckian algorithm, IL- 23p19, IL-1

Allopolyploid speciation and ongoing backcrossing between diploid progenitor and tetraploid progeny lineages in the Achillea millefolium species complex: analyses of single-copy nuclear genes and genomic AFLP

<p>Abstract</p> <p>Background</p> <p>In the flowering plants, many polyploid species complexes display evolutionary radiation. This could be facilitated by gene flow between otherwise separate evolutionary lineages in contact zones. <it>Achillea collina </it>is a widespread tetraploid species within the <it>Achillea millefolium </it>polyploid complex (Asteraceae-Anthemideae). It is morphologically intermediate between the relic diploids, <it>A. setacea</it>-2x in xeric and <it>A. asplenifolia</it>-2x in humid habitats, and often grows in close contact with either of them. By analyzing DNA sequences of two single-copy nuclear genes and the genomic AFLP data, we assess the allopolyploid origin of <it>A. collina</it>-4x from ancestors corresponding to <it>A. setacea</it>-2x and <it>A. asplenifolia</it>-2x, and the ongoing backcross introgression between these diploid progenitor and tetraploid progeny lineages.</p> <p>Results</p> <p>In both the ncp<it>GS </it>and the <it>PgiC </it>gene tree, haplotype sequences of the diploid <it>A. setacea</it>-2x and <it>A. asplenifolia</it>-2x group into two clades corresponding to the two species, though lineage sorting seems incomplete for the <it>PgiC </it>gene. In contrast, <it>A. collina</it>-4x and its suspected backcross plants show homeologous gene copies: sequences from the same tetraploid individual plant are placed in both diploid clades. Semi-congruent splits of an AFLP Neighbor Net link not only <it>A. collina</it>-4x to both diploid species, but some 4x individuals in a polymorphic population with mixed ploidy levels to <it>A. setacea</it>-2x on one hand and to <it>A. collina</it>-4x on the other, indicating allopolyploid speciation as well as hybridization across ploidal levels.</p> <p>Conclusions</p> <p>The findings of this study clearly demonstrate the hybrid origin of <it>Achillea collina</it>-4x, the ongoing backcrossing between the diploid progenitor and their tetraploid progeny lineages. Such repeated hybridizations are likely the cause of the great genetic and phenotypic variation and ecological differentiation of the polyploid taxa in <it>Achillea millefolium </it>agg.</p

Adaptive Dynamic Surface Control for Generator Excitation Control System

For the generator excitation control system which is equipped with static var compensator (SVC) and unknown parameters, a novel adaptive dynamic surface control scheme is proposed based on neural network and tracking error transformed function with the following features: (1) the transformation of the excitation generator model to the linear systems is omitted; (2) the prespecified performance of the tracking error can be guaranteed by combining with the tracking error transformed function; (3) the computational burden is greatly reduced by estimating the norm of the weighted vector of neural network instead of the weighted vector itself; therefore, it is more suitable for the real time control; and (4) the explosion of complicity problem inherent in the backstepping control can be eliminated. It is proved that the new scheme can make the system semiglobally uniformly ultimately bounded. Simulation results show the effectiveness of this control scheme

Cognitive-enhancing effects of polygalasaponin hydrolysate in aβ(25-35)-induced amnesic mice.

Polygalasaponins are the major active constituents of Polygala tenuifolia exhibiting antiamnesic activity, but their applications are limited due to their toxicities. Evidence showed that the toxicities can be attenuated by hydrolysis. Herein, effects of a hydrolysate of polygalasaponins (HPS) on cognitive impairment induced by Aβ(25-35) were assessed by Morris water maze and step-through passive avoidance tests. The impaired spatial reference memory was improved by HPS (50 and 100 mg/kg). In the acquisition trial of step-through test, HPS (50 and 100 mg/kg) increased the latency into the dark chamber and decreased the error frequency significantly (P < .05). However, no significant change was observed during the retention trial. Additionally, HPS increased the corresponding SOD activities (62.34%, 22.09%) and decreased MDA levels (28.21%, 32.35%) in both cortex and hippocampus as compared to model animals. These results show that HPS may be a useful treatment against amnesia probably via its antioxidant properties.Peer Reviewe

Cognitive-enhancing effects of polygalasaponin hydrolysate in aβ(25-35)-induced amnesic mice.

Polygalasaponins are the major active constituents of Polygala tenuifolia exhibiting antiamnesic activity, but their applications are limited due to their toxicities. Evidence showed that the toxicities can be attenuated by hydrolysis. Herein, effects of a hydrolysate of polygalasaponins (HPS) on cognitive impairment induced by Aβ25−35 were assessed by Morris water maze and step-through passive avoidance tests. The impaired spatial reference memory was improved by HPS (50 and 100mg/kg). In the acquisition trial of step-through test, HPS (50 and 100mg/kg) increased the latency into the dark chamber and decreased the error frequency significantly (P < .05). However, no significant change was observed during the retention trial. Additionally, HPS increased the corresponding SOD activities (62.34%, 22.09%) and decreased MDA levels (28.21%, 32.35%) in both cortex and hippocampus as compared to model animals. These results show that HPS may be a useful treatment against amnesia probably via its antioxidant properties

NaI (Tl) Calorimeter Calibration and Simulation for Coulomb Sum Rule Experiment in Hall-A at Jefferson Lab

A precision measurment of inclusive electron scattering cross sections was carried out at Jefferson Lab in the quasi-elastic region for ${^4}$He, ${^{12}}$C, ${^{56}}$Fe and ${^{208}}$Pb targets. Longitudinal ($R_{L}$) and transverse ($R_{T}$) response functions of nucleon were extracted in the momentum transfer range 0.55 GeV/c$\le$$|q|$$\le$1.0 GeV/c. To achieve the above goal, a NaI (Tl) calorimeter was used to distinguish good electrons from background including pions and low energy electrons rescattered from walls of the spectrometer magnets. Due to a large set of kinematics and changes in HV settings, a number of calibrations were performed for the NaI (Tl) detector. Corrections for a few blocks of NaI (Tl) with bad or no signal were applied. The resolution of NaI (Tl) detector after calibration reached $\frac{\delta E}{\sqrt{E}} \approx 3\%$ at E=1 GeV. The performance of NaI (Tl) detector was compared with a simulation