Point mutations in the different domains of the plasma membrane PMA1 ATPase cause redistribution among fractions of inorganic polyphosphates.

Both ATP and inorganic polyphosphates (PolyP) appeared to be involved in the yeast energy homeostasis, in which plasma membrane PMA1 H-АТРase plays one of the key roles. During biogenesis and functioning, the enzyme undergoes structural and regulatory phosphorylation. Aim of the work was to elucidate interconnection between functioning of the yeast PMA1 H-АТРase carrying point substitutions that affected the enzyme structure-function relationship and its ability to be phosphorylated and PolyP metabolism.

Point mutations in the extracytosolic loop between transmembrane segments M5 and M6 of the yeast Pma1 H+-ATPase: alanine-scanning mutagenesis.

Membrane-spanning segments M4, M5, M6, and M8 of the H(+)-, Ca(2+)-, and K(+), Na(+)-ATPases, which belong to the P2-type pumps are the core through which cations are transported. M5 and M6 loop is a short extracytoplasmic stretch of the seven amino acid residues (714-DNSLDID) connecting two of these segments, M5 and M6, where residues involved in the formation of the proton-binding site(s) are located. In the present study, we have used alanine-scanning mutagenesis to explore the structural and functional relationships within this loop of the yeast plasma membrane Pma1 H(+)-ATPase.

Structure-function relationships in membrane segment 6 of the yeast plasma membrane Pma1 H(+)-ATPase.

The crystal structures of the Ca(2+)- and H(+)-ATPases shed light into the membrane embedded domains involved in binding and ion translocation. Consistent with site-directed mutagenesis, these structures provided additional evidence that membrane-spanning segments M4, M5, M6 and M8 are the core through which cations are pumped. In the present study, we have used alanine/serine scanning mutagenesis to study the structure-function relationships within M6 (Leu-721-Pro-742) of the yeast plasma membrane ATPase.

Brain targeting of nerve growth factor using poly(butyl cyanoacrylate) nanoparticles.

The nerve growth factor (NGF) is essential for the survival of both peripheral ganglion cells and central cholinergic neurons in the basal forebrain. The accelerated loss of central cholinergic neurons during Alzheimer's disease may be a determinant cause of dementia, and this observation may suggest a possible therapeutic benefit from treatment with NGF. In recent years, convincing data have been published involving neurotrophic factors for the modulation of dopaminergic transmission within the brain and concerning the ability of NGF to prevent the degeneration of dopaminergic neurons.

Role of transmembrane segment M8 in the biogenesis and function of yeast plasma-membrane H(+)-ATPase.

Of the four transmembrane helices (M4, M5, M6, and M8) that pack together to form the ion-binding sites of P(2)-type ATPases, M8 has until now received the least attention. The present study has used alanine-scanning mutagenesis to map structure-function relationships throughout M8 of the yeast plasma-membrane H(+)-ATPase. Mutant forms of the ATPase were expressed in secretory vesicles and at the plasma membrane for measurements of ATP hydrolysis and ATP-dependent H(+) pumping.

Nonlinear prediction, filtering, and control of chemical systems from time series.

Prediction, filtering and control of nonlinear systems is formulated in terms of corresponding nonlinear surfaces in the phase space of delayed system readings and control parameters. The construction of these surfaces from time series and their use is demonstrated with a simple chemical model in the chaotic regime. (c) 1997 American Institute of Physics.

Direct evidence that polysorbate-80-coated poly(butylcyanoacrylate) nanoparticles deliver drugs to the CNS via specific mechanisms requiring prior binding of drug to the nanoparticles.

Purpose: [corrected] It has recently been suggested that the poly(butylcyanoacrylate) (PBCA) nanoparticle drug delivery system has a generalized toxic effect on the blood-brain barrier (BBB) (8) and that this effect forms the basis of an apparent enhanced drug delivery to the brain. The purpose of this study is to explore more fully the mechanism by which PBCA nanoparticles can deliver drugs to the brain.

Methods: Both in vivo and in vitro methods have been applied to examine the possible toxic effects of PBCA nanoparticles and polysorbate-80 on cerebral endothelial cells.

Apolipoprotein-mediated transport of nanoparticle-bound drugs across the blood-brain barrier.

Recent studies have shown that drugs that are normally unable to cross the blood-brain barrier (BBB) following intravenous injection can be transported across this barrier by binding to poly(butyl cyanoacrylate) nanoparticles and coating with polysorbate 80. However, the mechanism of this transport so far was not known. In the present paper, the possible involvement of apolipoproteins in the transport of nanoparticle-bound drugs into the brain is investigated.