Divalent cation-induced aggregation of chromaffin granule membranes.

Divalent cations induce the aggregation of chromaffin granule ghosts (CG membranes) at millimolar concentrations. Monovalent cations produce the same effect at 100-fold higher concentrations. The kinetics of the dimerization phase were followed by light-scattering changes observed in stopped-flow rapid mixing experiments. The rate constant for Ca2+-induced dimerization (kapp) is 0.86-1.0 x 10(9) M-1sec-1, based on the "molar" vesicle concentration. This value is close to the values predicted by theory for the case of diffusion-controlled reaction (7.02 x 10(9) M-1sec-1), indicating that there is no energy barrier to dimerization. Arrhenius plots between 10 degrees and 42 degrees C support this; the activation energy observed, +4.4 Kcal, is close to the value (4.6-4.8 Kcal) predicted for diffusion control according to theory. Artificial vesicles prepared from CG lipids were also found to have cation-induced aggregation, but the rates (values of kapp) were less than 1/100 as large as those with native CG membranes. Also, significant differences were found with respect to cation specificity. It is concluded that the slow rates are due to the low probability that the segments of membrane which approach will be matched in polar head group composition and disposition. Thus large numbers of approaches are necessary before matched segments come into aposition. The salient features of the chromaffin granule membrane aggregation mechanism are as follows: (a) In the absence of cations capable of shielding and binding, the membranes are held apart by electrostatic repulsion of their negatively charged surfaces. (b) The divalent and monovalent cation effects on aggregation are due to their ability to shield these charges, allowing a closer approach of the membrane surfaces. (c) The major determinants of the aggregation rates of CG membranes are proteins which protrude from the (phospholipid) surface of the membrane and serve as points of primary contact. Transmembrane contact between these proteins does not require full neutralization of the surface charge and surface potential arising from the negatively charged phospholipids. (d) After contact between proteins is established, the interaction between membranes can be strengthened through transmembrane hydrogen bonding of phosphatidyl ethanolamine polar head groups, divalent cation-mediated salt bridging, and segregation of phosphatidylcholine out of the region of contact.     

Electromyographic biofeedback treatment of a woman with chronic dysphagia

In this case report, a 25-year-old female with chronic dysphagia spastica(difficulty swallowing because of constriction of the throat muscles) was treated with 20 sessions of frontal electromyographic(EMG) biofeedback and home-relaxation practice. The subject monitored on a 10-point scale her difficulty swallowing during meals for 2 months prior to treatment, during treatment, and after treatment. There was a significant decrease in reported difficulty swallowing associated with frontalis EMG feedback. Improvement was maintained at a 6-month follow-up.     

Isolation and characterization of yeast mutants auxotrophic for 2''-deoxythymidine 5''-monophosphate.

Summary Mutant strains of Saccharomyces cerevisiae auxotrophic for deoxythymidine monophosphate (dTMP) were isolated and characterized. Two distinct classes of auxotrophs were obtained. One class had a simple requirement for dTMP and was analogous to thymine-requiring bacteria. The second class required dTMP, adenine, histidine and methionine and this complex nutritional phenotype was due to defects in folate metabolism. The dTMP-dependent growth of respiratory-competent grande auxotrophs was found to be markedly affected by media composition and carbon source. In the absence of dTMP thymineless death occurred in both mutant classes.     

Antimalarial drugs impact chemical messenger secretion by blood platelets

BackgroundAdvances in antimalarial drug development are important for combating malaria. Among the currently identified antimalarial drugs, it is suggested that some interact directly with the malarial parasites while others interact indirectly with the parasites. While this approach leads to parasite elimination, little is known about how these antimalarial drugs impact immune cells that are also critical in malarial response.MethodsHerein, the effects of two common antimalarial drugs, chloroquine and quinine, on platelets were explored at both the bulk level, using high performance liquid chromatography, and the single cell level, using carbon-fiber microelectrode amperometry, to characterize any changes in chemical messenger secretion.ResultsThe data reveal that both drugs cause platelet activation and reduce the number of platelet exocytosis events as well as delay fusion pore opening and closing.ConclusionsThis work demonstrates how chloroquine and quinine quantitatively and qualitatively impact in vitro platelet function.General significanceOverall, the goal of this work is to promote understanding about how antimalarial drugs impact platelets as this may affect antimalarial drug development as well as therapeutic approaches to treat malarial infection.     

Beyond ecosystem modeling: A roadmap to community cyberinfrastructure for ecological data‐model integration

In an era of rapid global change, our ability to understand and predict Earth's natural systems is lagging behind our ability to monitor and measure changes in the biosphere. Bottlenecks to informing models with observations have reduced our capacity to fully exploit the growing volume and variety of available data. Here, we take a critical look at the information infrastructure that connects ecosystem modeling and measurement efforts, and propose a roadmap to community cyberinfrastructure development that can reduce the divisions between empirical research and modeling and accelerate the pace of discovery. A new era of data‐model integration requires investment in accessible, scalable, and transparent tools that integrate the expertise of the whole community, including both modelers and empiricists. This roadmap focuses on five key opportunities for community tools: the underlying foundations of community cyberinfrastructure; data ingest; calibration of models to data; model‐data benchmarking; and data assimilation and ecological forecasting. This community‐driven approach is a key to meeting the pressing needs of science and society in the 21st century.