Temperament and substance abuse in schizophrenia: is there a relationship?

Dyspnea may be easily appreciated during exercise with dyspneic scales, but methodological standardisation still needs to be specified. Authors review the basic physiological mechanism relating dyspnea to indices obtained during a stress test. They propose to use the dyspnea/VE relationship. With the concept of dyspneic threshold (close to the ventilatory threshold) and the ramp that both could be modified (for instance by rehabilitation programmes including exercise training). Interpretation of dyspnea during an exercise test obviously needs to be integrated with other parameters studied during exercise.     

Is there a direct relationship between oral astringency and human salivary protein binding?

For decades, it is believed that astringency is due to the polyphenol-induced complexation of proline-rich salivary proteins in the oral cavity. In order to compare for the first time the human sensory threshold concentrations and the salivary protein binding activity of a series of astringent stimuli, human saliva protein was incubated for 5 min at 37 °C in the presence of astringent food-derived compounds and, after micro-centrifugation, the amount of the target molecules in the supernatant was quantitatively determined by HPLC-UV/Vis. Significant protein binding was observed for (−)-epigallocatechin-3-gallate, (−)-gallocatechin-3-gallate, (+)-gallocatechin, and (−)-catechin-3-gallate, all of which containing at least one galloyl moiety in the molecule and exhibiting rather high sensory thresholds of more than 200 μmol/L. In comparison, (+)-catechin and procyanidin B2, both lacking in any galloyl function, showed only comparatively low binding activity and, most interestingly, quercetin-3-O-α-l-rhamnopyranosyl-(1 → 6)-β-d-glucopyranoside and 3-carboxymethyl-indole-1-N-β-d-glucopyranoside did not show any protein binding at all, although the later N- and O-glycosides exhibited extraordinarily low sensory threshold concentrations of less than 0.001 and 0.0003 μmol/L, respectively. The data give some first evidence that the quantity of the non-bound, “free” astringent stimulus in the saliva liquid might be more closely related to the sensory perception of astringency than the amount complexed or precipitated by proteins. It is therefore questionable as to whether oral perception of astringency is related to the complexation and/or precipitation of salivary proteins.     

Slip Control System for a Deep-Sea Mining Machine

Tracked vehicles capable of locomotion in the deep sea are used for manganese nodule mining. This requires specific technical solutions in various respects. Locomotion in the soft sea bed is one of them. For the Crawler to safely maneuver, an automatic drive mode with slip control of the driving tracks is essential. Based on experimental studies at IKS, University of Siegen, slip control for the NIOT-IKS mining machine has been developed and implemented. The experimental setup for the development of the slip control along with the logic of the automatic driving mode is described. The system is critically discussed and the test results and future work are briefly outlined. Note to Practitioners-The work is carried out as part of the polymetallic nodule mining program of the Government of India. The technique of slip control is a specific requirement for a tracked vehicle used in the deep sea. Slip is common in many vehicles-tracked and otherwise. Examples are steam engines in the early days and ordinary cars while negotiating slush or snow/ice and dozers working in soft soil. While these are manually controlled by drivers who have firsthand knowledge of the environmental conditions, in the case of a mining machine in deep sea, it has to be completely automatic and, hence, is challenging. The knowledge generated in this work could be effectively used by practitioners in other related areas of automobile engineering for updating their expertise. Also, similar techniques may be used for maneuvering vehicles sent to other planets     

General acid/base catalysis in the active site of Escherichia coli thioredoxin

Enzymic catalysts of thiol:disulfide oxidoreduction contain two cysteine residues in their active sites. Another common residue is an aspartate (or glutamate), the role of which has been unclear. Escherichia coli thioredoxin (Trx) is the best characterized thiol:disulfide oxidoreductase, and in Trx these three active-site residues are Cys32, Cys35, and Asp26. Structural analyses had indicated that the carboxylate of Asp26 is positioned properly for the deprotonation of the thiol of Cys35, which would facilitate its attack on Cys32 in enzyme-substrate mixed disulfides. Here, Asp26 of Trx was replaced with isologous asparagine and leucine residues. D26N Trx and D26L Trx are reduced and oxidized more slowly than is wild-type Trx during catalysis by E.coli thioredoxin reductase. Stopped-flow spectroscopy demonstrated that the cleavage of the mixed disulfide between Trx and a substrate is slower in the D26N and D26L enzymes. Buffers increase the rate of mixed disulfide cleavage in these variants but not in wild-type Trx. These results indicate that Asp26 serves as an acid/base in the oxidation/reduction reactions catalyzed by Trx. Specifically, Asp26 protonates (during substrate oxidation) or deprotonates (during substrate reduction) the thiol of Cys35. A similar role is likely filled by the analogous aspartate (or glutamate) residue in protein disulfide isomerase, DsbA, and other thiol:disulfide oxidoreductases. Moreover, these results provide the first evidence for general acid/base catalysis in a thiol:disulfide interchange reaction.     

In vitro cytotoxicity and DNA damage production in Chinese hamster ovary cells and topoisomerase II inhibition by 2-[2''-(dimethylamino)ethyl]-1, 2-dihydro-3H-dibenz[de,h]isoquinoline-1,3-diones with substitutions at the 6 and 7 positions (azonafides)

The p53 tumor suppressor gene encodes a phosphoprotein which when overexpressed can induce growth arrest at the G1 and G2/M phases of the cell cycle, promote differentiation and apoptosis. This paper demonstrates that p53 can associate with trk tyrosine kinase. Expression of a murine temperature-sensitive (ts) p53 mutant in PC12 cells overexpressing trk (a model system to analyse cellular differentiation and signal transduction induced by NGF) induces morphological changes in the absence of NGF stimulation at 32 degrees C but not at 37 degrees C. In cells differentiated by p53, trk, but not EGFr, was hyperphosphorylated on tyrosine. Furthermore trk was not phosphorylated when expressed in Saos-2 cells (human osteosarcoma cells that lack expression of both endogenous trk and p53) at either temperature. However, transfection of ts p53 into these cells induces trk phosphorylation at 32 degrees C in the absence of NGF stimulation. Association of trk and p53 can be detected in NIH3T3 and PC12 cells co-expressing trk and the ts p53 mutant, in NIH3T3 and PC12 cells transfected with trk alone, and in untransfected PC12 cells, showing that overexpressed and/or endogenous trk associates with endogenous, low levels of p53. These data suggest a novel function for p53 which involves the stimulation of signal transduction pathways (mediating morphological properties of cells), possibly through association with and hyperphosphorylation of trk.