Optical quantal analysis reveals a presynaptic component of LTP at hippocampal Schaffer-associational synapses

The mechanisms by which long-term potentiation (LTP) is expressed are controversial, with evidence for both presynaptic and postsynaptic involvement. We have used confocal microscopy and Ca(2+)-sensitive dyes to study LTP at individual visualized synapses. Synaptically evoked Ca(2+) transients were imaged in distal dendritic spines of pyramidal cells in cultured hippocampal slices, before and after the induction of LTP. At most synapses, from as early as 10 min to at least 60 min after induction, LTP was associated with an increase in the probability of a single stimulus evoking a postsynaptic Ca(2+) response. These observations provide compelling evidence of a presynaptic component to the expression of early LTP at Schaffer-associational synapses. In most cases, the store-dependent evoked Ca(2+) transient in the spine was also increased after induction, a novel postsynaptic aspect of LTP.     

A thin-film electrochemical study of the "blue" copper proteins,auracyanin A and auracyanin B,from the photosynthetic bacterium <Emphasis Type="Italic">Chloroflexus</Emphasis><Emphasis Type="Italic">aurantiacus</Emphasis>: the reduction potential as a function of pH

The reversible formal potentials of auracyanin A and auracyanin B, two closely related "blue" copper proteins from the photosynthetic bacterium Chloroflexus aurantiacus, have been determined by protein film voltammetry in the range 4相似文献   

Illuminating adhesion complexes in migrating cells: moving toward a bright future

Cell migration is a complex, tightly regulated process that involves the continuous formation and disassembly of adhesions. Despite the importance of these processes, very little is known about the factors that regulate adhesion dynamics during migration. Recent advances in imaging technologies are allowing monitoring of these processes during migration and are providing insight into the mechanisms that regulate them.     

Evidence that acetyl phosphate functions as a global signal during biofilm development

We used DNA macroarray analysis to identify genes that respond to the status of the intracellular acetyl phosphate (acP) pool. Genes whose expression correlated negatively with the ability to synthesize acP (i.e. negatively regulated genes) function primarily in flagella biosynthesis, a result consistent with observations that we published previously (Prüss and Wolfe, 1994, Mol Microbiol 12: 973-984). In contrast, genes whose expression correlated positively with the ability to synthesize acP (i.e. positively regulated genes) include those for type 1 pilus assembly, colanic acid (capsule) biosynthesis and certain stress effectors. To our knowledge, this constitutes the first report that these genes may respond to the status of the intracellular acP pool. Previously, other researchers have implicated flagella, type 1 pili, capsule and diverse stress effectors in the formation of biofilms. We therefore tested whether cells altered in their ability to metabolize acP could construct normal biofilms, and found that they could not. Cells defective for the production of acP and cells defective for the degradation of acP could both form biofilms, but these biofilms exhibited characteristics substantially different from each other and from biofilms formed by their wild-type parent. We confirmed the role of individual cell surface structures, the expression of which appears to correlate with acP levels, in fim or fli mutants that cannot assemble type 1 pili or flagella respectively. Thus, the information gained by expression profiling of cells with altered acP metabolism indicates that acP may help to co-ordinate the expression of surface structures and cellular processes involved in the initial stages of wild-type biofilm development.     

High affinity, bioavailable 3-amino-1,4-benzodiazepine-based gamma-secretase inhibitors

In this paper, we describe the development of a novel series of high affinity, orally bioavailable 3-amino-1,4 benzodiazepine-based gamma-secretase inhibitors for the potential treatment of Alzheimer's disease. We disclose structure-activity relationships based around the 1, 3 and 5 positions of the benzodiazepine core structure.     

Response of cancer cells to molecular interruption of the CK2 signal

Protein kinase CK2 is one of the key cellular signals for cell survival, growth, and proliferation. It is has been observed to be elevated in various cancers that have been examined. Various observations suggest that moderate dysregulation of CK2 may profoundly influence the cell response. We have examined the effects of interfering with the CK2 signal in various cancer cell lines by employing antisense oligodeoxynucleotides (ODN) against the and subunits of CK2. Our results demonstrate that antisense CK2- and antisense CK2- ODNs markedly influence cell viability of these cancer cells in a dose and time-dependent manner. Antisense CK2- was slightly more effective than antisense CK2- in most of the cells tested. The efficacy of the antisense ODN seemed to vary with the cell type; however, in all cases potent induction of apoptosis was observed. Significantly, the effects of the antisense ODN on the CK2 activity in the nuclear matrix were relatively small compared to the much stronger induction of apoptosis in cells. This suggests that modest down-regulation of CK2 can evoke a much greater apoptotic response in cancer cells.     

Random binding of dimers to chains

We develop a probabilistic model for the binding of a small linear polymer to a larger chain. We assume that we can approximate the energy of interaction of the two chains by summing the pairwise interactions between subunits. Because the energy of interaction between a pair of subunits can depend on neighboring subunits, which we assume vary along the chain, we assign the pairwise energies of interactions according to a specified probability distribution. Thus we develop a statistical model for the binding of two molecules. While such models may not be appropriate for studying the interaction of a particular pair of molecules, they can provide insight into questions that deal with populations of molecules, such as why do MHC molecules bind peptides of a certain size? Here we analyze in detail the special case of a heterodimer binding to a polymer.