Eye movements induced by lateral acceleration steps. Effect of visual context and acceleration levels

Different extracellular matrix (ECM) molecules, when presented to hippocampal neurons in culture in a substrate-bound form, exert strikingly similar effects on the establishment of neuronal polarity, i.e., the growth of axon-like major neurites is favored, whereas extension of dendrite-like minor neurites is inhibited. To gain insight into the underlying signal transduction processes, we have investigated the effects of modulators of protein kinase activity on the morphology of neurons cultured on tenascin-R, tenascin-C, and laminin-entactin substrates. We found differential effects of broad-spectrum protein kinase inhibitors: H-7 promoted the growth of minor neurites, whereas H-8 reduced the growth of major neurites on ECM but not control substrates. In contrast, chelerythrine, a specific inhibitor of protein kinase C, selectively affected growth of both minor and major neurites on control, but not on ECM substrates. Finally, reagents which elevate intracellular cAMP levels facilitated growth of minor neurites and inhibited growth of major neurites and thus interfered with the establishment of a polarized phenotype on both ECM and control substrates. Our results suggest that protein kinases mediate the effects of ECM molecules on neuronal polarity and that different kinases control extension of axons and dendrites.     

Effects of different doses of apomorphine on the glutamate decarboxylase activity of the substantia nigra and the medial basal hypothalamus

The activity of gamma-aminobutyric acid (GABA) synthesizing enzyme glutamic acid decarboxylase (GAD, EC 4.1.1.15) was assayed in the rat substantia nigra (SN) and medial basal hypothalamus (MBH) following systemic injection of different doses of the dopamine receptor agonist apomorphine. In SN, the highest dose of apomorphine (1000 micrograms/kg) causes an increase of the GAD activity whilst an opposite effect is observed with the lowest dose (35 micrograms/kg). Results obtained in SN are in accordance with previous neurochemical and behavioural data suggesting an opposite action of high (500 micrograms/kg) and low doses (100 micrograms/kg) of apomorphine in nigro-striatal system, probably due to the existence of two classes of dopamine receptors, i.e. classical postsynaptic dopamine receptors and presynaptic inhibitory dopamine autoreceptors. In MBH, the evidence for similar effects of low and high doses of apomorphine (the decrease of GAD activity) may suggest that, as already reported, at this level only one class of dopamine receptors is present.     

Effect of Glu-143 and His-231 substitutions on the catalytic activity and secretion of Bacillus subtilis neutral protease

On the basis of the homology with the Bacillus thermoproteolyticuszinc endopeptidase thermotysin, we hypothesized that Glu-143and His-231 are the key residues for the catalytic activityof the Bacillus subtilis neutral protease. To test this possibilityby site-directed mutagenesis, we substituted these two residueswith Ala, Ser, Trp and Arg, and Leu, Val and Cys respectively.All these substitutions dramatically affected the amount ofsecreted mutant proteins, as determined by immunological methods,and their catalytic activities. No appreciable secretion wasobserved with the three Glu mutants Trp, Ser and Arg, whereasthe Glu–Ala mutant enzyme was secreted at a level of afew hundred micrograms per litre of culture. The His mutantswere all secreted at higher levels (in the order of a few milligramsper litre) and their residual catalytic activity could be determinedusing Z-Ala-Leu-Ala as substrate. Our results confirm the keyrole played by Glu-143 and His-231 in catalysis and moreoversuggest the existence of a relationship between the catalyticactivity of the enzyme and the extent of its secretion. In thiscontext, we present data suggesting an autoproteolytic mechanismof cleavage of the precursor form of the enzyme, analogous tothe one previously reported for the B.subtilis subtilisin.     

Identification and analysis of isothiocyanates and new acylated anthocyanins in the juice of Raphanus sativus cv. Sango sprouts

The freeze-dried sprouts’ juice of Raphanus sativus (L.) cv. Sango was prepared and analysed for the first time. HPLC analysis of total isothiocyanates, after protein displacement, resulted in 77.8 ± 3.0 μmol/g of dry juice while GC–MS analysis of hexane and acetone extracts showed E- and Z-raphasatin (8.9 and 0.11 μmol/g, respectively) and sulforaphene (11.7 μmol/g), summing up to 20.7 ± 1.7 μmol/g of free isothiocyanates. Sprouts’ juice contained an unprecedented wealth of anthocyanins and a new fractionation methodology allowed us to isolate 34 mg/g of acylated anthocyanins (28.3 ± 1.9 μmol/g), belonging selectively to the cyanidin family. Analysis was performed by HPLC–PDA–ESI–MSⁿ and extended to deacylated anthocyanins and aglycones, obtained, respectively, by alkaline and acid hydrolysis. This study identified 70 anthocyanins, 19 of which have never been described before and 32 of which are reported here in R. sativus for the first time. Sango radish sprouts are exceptional dietary sources of heath-promoting micronutrients.     

On the design of the RTO unit using CFD

The objective of this work is to study alternative designs for a flow mixing tank to be installed ahead of a regenerative thermal oxidation (RTO) unit in an asphalt plant. A study of the steady-state flow field in the unit was conducted applying computational fluid dynamics (CFD). The governing equations (mass, momentum, energy and turbulence) were solved using the commercial code Fluent. The simulation results provided insight into the effectiveness of the numerical predictions of conditions in the mixer and led to practical responses in terms of a better design of the industrial RTO unit.     

The development of epistemological beliefs among secondary students: A longitudinal study.

This article is the continuation of M. Schommer's (1993) study, in which the development of secondary students' beliefs about the nature of knowledge and learning, or epistemological beliefs, was examined. High school students (N?=?69) completed an epistemological questionnaire as freshmen in 1992 and as seniors in 1995. Repeated-measures analyses revealed that their beliefs in fixed ability to learn, simple knowledge, quick learning, and certain knowledge changed as they neared the end of their 4th year in high school. In addition, the less students believed in quick learning, the better grade point average they earned. These results are consistent with a cross-sectional study (M. Schommer, 1993) establishing substantial differences in students' epistemological beliefs across the high school years and thus strengthen the case that there is development of epistemological beliefs related to learning during high school. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Local controllability of non-linear systems: An example

An example of a locally controllable nonlinear system on R³ is given. The system is of the type with f, g analytic vector fields and u bounded. The fields f and g are such that the dimension of the vector space spanned at x₀ by the Lie brackets which contain g an odd number of times is 2.     

Decay-accelerating factor (CD55) and membrane inhibitor of reactive lysis (CD59) are released within exosomes during In vitro maturation of reticulocytes

Exosomes are membrane vesicles released by reticulocytes during their maturation into erythrocytes. They have a clearing function because of their enrichment with some proteins known to decrease or disappear from the cell surface during maturation, eg, acetylcholinesterase (AChE) and transferrin receptor (TfR), respectively. To better understand the molecular events leading to protein sorting in exosomes, we analyzed the expression of glycosylphosphatidylinositol (GPI)-anchored proteins on the exosome surface through a technique involving bead coupling and flow cytometry immunodetection. The presence of AChE, decay-accelerating factor (DAF), membrane inhibitor of reactive lysis (MIRL), and lymphocyte function-associated antigen 3 (LFA-3) on the surface of exosomes obtained from normal and paroxysmal nocturnal hemoglobinuria (PNH) reticulocytes, suggests that (1) the GPI anchor is efficiently sorted during exosome formation, (2) exosome release could account for the observed discrepancy in GPI-protein expression between reticulocytes and erythrocytes from PNH patients, and (3) exosomes could have another physiologic function related to controlling membrane attack complex formation.     

Synthesis,Pharmacological Evaluation,and Docking Studies of Novel Pyridazinone‐Based Cannabinoid Receptor Type 2 Ligands

In recent years, cannabinoid type 2 receptors (CB₂R) have emerged as promising therapeutic targets in a wide variety of diseases. Selective ligands of CB₂R are devoid of the psychoactive effects typically observed for CB₁R ligands. Based on our recent studies on a class of pyridazinone 4‐carboxamides, further structural modifications of the pyridazinone core were made to better investigate the structure–activity relationships for this promising scaffold with the aim to develop potent CB₂R ligands. In binding assays, two of the new synthesized compounds [6‐(3,4‐dichlorophenyl)‐2‐(4‐fluorobenzyl)‐cis‐N‐(4‐methylcyclohexyl)‐3‐oxo‐2,3‐dihydropyridazine‐4‐carboxamide ( 2 ) and 6‐(4‐chloro‐3‐methylphenyl)‐cis‐N‐(4‐methylcyclohexyl)‐3‐oxo‐2‐pentyl‐2,3‐dihydropyridazine‐4‐carboxamide ( 22 )] showed high CB₂R affinity, with K_i values of 2.1 and 1.6 nm , respectively. In addition, functional assays of these compounds and other new active related derivatives revealed their pharmacological profiles as CB₂R inverse agonists. Compound 22 displayed the highest CB₂R selectivity and potency, presenting a favorable in silico pharmacokinetic profile. Furthermore, a molecular modeling study revealed how 22 produces inverse agonism through blocking the movement of the toggle‐switch residue, W6.48.