THE "BOUND" WATER OF BIOLOGICAL COLLOIDS: A REPLY

The objection by Bull to the estimation of bound water by ultrafiltration, because of an assumed adsorption of the reference substance, has been found invalid for glucose. No adsorption of glucose by the proteins, casein and gelatin, could be detected. The estimation of the bound water of proteins from the probable surface adsorption of water by proteins leads to only a small value.     

Die physikalische Chemie der Eiweissk?rper

Ohne Zusammenfassung(Deutsche Übertragung von FrauElse Asher.)Einige Abschnitte, die für diesen Teil bestimmt waren, mussten wegen Krankheit des Autors, und, um die Veröffentlichung nicht zu verzögern, auf den später erscheinenden zweiten Teil verschoben werden.Die Herausgeber.     

Specific inhibition of the plasmodial surface anion channel by dantrolene

The plasmodial surface anion channel (PSAC), induced on human erythrocytes by the malaria parasite Plasmodium falciparum, is an important target for antimalarial drug development because it may contribute to parasite nutrient acquisition. However, known antagonists of this channel are quite nonspecific, inhibiting many other channels and carriers. This lack of specificity not only complicates drug development but also raises doubts about the exact role of PSAC in the well-known parasite-induced permeability changes. We recently identified a family of new PSAC antagonists structurally related to dantrolene, an antagonist of muscle Ca++ release channels. Here, we explored the mechanism of dantrolene's actions on parasite-induced permeability changes. We found that dantrolene inhibits the increased permeabilities of sorbitol, two amino acids, an organic cation, and hypoxanthine, suggesting a common pathway shared by these diverse solutes. It also produced parallel reductions in PSAC single-channel and whole-cell Cl- currents. In contrast to its effect on parasite-induced permeabilities, dantrolene had no measurable effect on five other classes of anion channels, allaying concerns of poor specificity inherent to other known antagonists. Our studies indicate that dantrolene binds PSAC at an extracellular site distinct from the pore, where it inhibits the conformational changes required for channel gating. Its affinity for this site depends on ionic strength, implicating electrostatic interactions in dantrolene binding. In addition to the potential therapeutic applications of its derivatives, dantrolene's specificity and its defined mechanism of action on PSAC make it a useful tool for transport studies of infected erythrocytes.     

Planktonic aggregates of Staphylococcus aureus protect against common antibiotics

Bacterial cells are mostly studied during planktonic growth although in their natural habitats they are often found in communities such as biofilms with dramatically different physiological properties. We have examined another type of community namely cellular aggregates observed in strains of the human pathogen Staphylococcus aureus. By laser-diffraction particle-size analysis (LDA) we show, for strains forming visible aggregates, that the aggregation starts already in the early exponential growth phase and proceeds until post-exponential phase where more than 90% of the population is part of the aggregate community. Similar to some types of biofilm, the structural component of S. aureus aggregates is the polysaccharide intercellular adhesin (PIA). Importantly, PIA production correlates with the level of aggregation whether altered through mutations or exposure to sub-inhibitory concentrations of selected antibiotics. While some properties of aggregates resemble those of biofilms including increased mutation frequency and survival during antibiotic treatment, aggregated cells displayed higher metabolic activity than planktonic cells or cells in biofilm. Thus, our data indicate that the properties of cells in aggregates differ in some aspects from those in biofilms. It is generally accepted that the biofilm life style protects pathogens against antibiotics and the hostile environment of the host. We speculate that in aggregate communities S. aureus increases its tolerance to hazardous environments and that the combination of a biofilm-like environment with mobility has substantial practical and clinical importance.     

Effect of parathyroid hormone on Na+-dependent phosphate transport and cAMP-dependent 32P phosphorylation in brush border vesicles from isolated perfused canine kidneys

Concentrative uptake of 32Pi induced by the dissipation of a Na+ gradient (overshoot) was demonstrated in brush border membrane vesicles obtained from isolated perfused canine kidneys. Na+-dependent 32Pi transport was decreased in brush border vesicles from isolated kidneys perfused with parathyroid hormone (PTH) for 2 h compared to uptake measured in vesicles from kidneys perfused without PTH. Cyclic AMP-dependent 32P phosphorylation of a 62,000 Mr protein band was demonstrable on autoradiograms of sodium dodecyl sulfate-polyacrylamide gels of membrane suspensions from kidneys perfused +/- PTH. Evidence that perfusion with PTH resulted in cAMP-dependent phosphorylation in isolated kidneys from parathyroidectomized dogs (decreased cAMP-dependent 32P phosphorylation of the 62,000-Mr band in brush border vesicles) was obtained after 2-h perfusion with PTH. Decreased 32P phosphorylation was not observed if membranes were allowed to dephosphorylate prior to 32P phosphorylation in vitro. We conclude that brush border vesicles from isolated perfused canine kidneys can be used to study the action of PTH on Na+-Pi cotransport in brush border membranes and on cAMP-dependent phosphorylation of the membrane. It is strongly suggested that PTH effects changes in Na+-dependent 32Pi transport in isolated brush border vesicles and changes in 32P phosphorylation of vesicles via a direct action on the renal cortical cell rather than as a consequence of extrarenal actions of the hormone.     

STUDIES IN THE PHYSICAL CHEMISTRY OF AMINO ACIDS,PEPTIDES, AND RELATED SUBSTANCES : XI. THE SOLUBILITY OF CYSTINE IN THE PRESENCE OF IONS AND ANOTHER DIPOLAR ION

1. As an introduction to the relations that obtain in biochemical systems containing several components, some ionic, some dipolar ionic, the solubility of cystine has been investigated in the presence of glycine and neutral salts. 2. Both glycine and sodium chloride increase cystine solubility at all concentrations. The interaction between cystine and ions is, however, diminished with increase in glycine concentration, and the interaction between cystine and glycine with increase in ionic strength. 3. Sodium sulfate also increases the solubility of cystine, but at concentrations greater than one molal its solvent action is smaller than its salting-out effect, which is greater at all concentrations than that of sodium chloride, and greater the higher the glycine concentration. 4. These interactions are defined by an equation giving the solubility ratio of cystine in terms of salting-out constants, constants related to the electric moments of cystine, and to the ionic strength and dielectric constant of the solution. 5. The higher the concentration of glycine and therefore the dielectric constant of the solution, the smaller that part of the interaction between ions and dipolar ions which depends upon Coulomb forces and the greater appears the salting-out effect. 6. Conversely, the greater the ionic strength and the salting-out effect the smaller the interaction between dipolar ions in solution.