Voltage-sensing residues in the S4 region of a mammalian K+ channel

The ability of ion-channel proteins to respond to a change of the transmembrane voltage is one of the basic mechanisms underlying electrical excitability of nerve and muscle membranes. The voltage sensor has been postulated to be the fourth putative transmembrane segment (S4) of voltage-activated Na+, Ca2+ and K+ channels. Mutations of positively charged residues within S4 alter gating of Na and Shaker-type K+ channels, but quantitative correlations between the charge or a residue in S4 and the gating valence of the channel have not yet been established. Here, with improved resolution of the voltage dependence of steady-state activation, we present estimates of the equivalent gating valence with sufficient precision to allow quantitative examination of the contribution of individual charged residues to the gating valence of a mammalian non-inactivating K+ channel. We conclude that at least part of the gating charge associated with channel activation is indeed contributed by charged residues within the S4 segment.     

Structure activity relationships of some centrally active dialkyl substituted propanediol sulfites

Résumé Une étude de 2-2-dialkyl-1-3-propanediol esters cyclique d'acide sulfureux constatait des filiations structure activité très interessantes. Avec un petit ralongant de la chaîne alkyl il est changé d'un stimulant système nerveux central (dimethyl, diethyl, et le pentaerythritol disulfite) à un dépressant système nerveux central fort modérément.     

Compositional homogeneity in the fragmented comet 73P/Schwassmann-Wachmann 3

The remarkable compositional diversity of volatile ices within comets can plausibly be attributed to several factors, including differences in the chemical, thermal and radiation environments in comet-forming regions, chemical evolution during their long storage in reservoirs far from the Sun, and thermal processing by the Sun after removal from these reservoirs. To determine the relevance of these factors, measurements of the chemistry as a function of depth in cometary nuclei are critical. Fragmenting comets expose formerly buried material, but observational constraints have in the past limited the ability to assess the importance of formative conditions and the effects of evolutionary processes on measured composition. Here we report the chemical composition of two distinct fragments of 73P/Schwassmann-Wachmann 3. The fragments are remarkably similar in composition, in marked contrast to the chemical diversity within the overall comet population and contrary to the expectation that short-period comets should show strong compositional variation with depth in the nucleus owing to evolutionary processing from numerous close passages to the Sun. Comet 73P/Schwassmann-Wachmann 3 is also depleted in the most volatile ices compared to other comets, suggesting that the depleted carbon-chain chemistry seen in some comets from the Kuiper belt reservoir is primordial and not evolutionary.     

Biological sensing of small field differences by magnetically sensitive chemical reactions

There is evidence that animals can detect small changes in the Earth's magnetic field by two distinct mechanisms, one using the mineral magnetite as the primary sensor and one using magnetically sensitive chemical reactions. Magnetite responds by physically twisting, or even reorienting the whole organism in the case of some bacteria, but the magnetic dipoles of individual molecules are too small to respond in the same way. Here we assess whether reactions whose rates are affected by the orientation of reactants in magnetic fields could form the basis of a biological compass. We use a general model, incorporating biological components and design criteria, to calculate realistic constraints for such a compass. This model compares a chemical signal produced owing to magnetic field effects with stochastic noise and with changes due to physiological temperature variation. Our analysis shows that a chemically based biological compass is feasible with its size, for any given detection limit, being dependent on the magnetic sensitivity of the rate constant of the chemical reaction.     

Mapping and sequencing of structural variation from eight human genomes

Genetic variation among individual humans occurs on many different scales, ranging from gross alterations in the human karyotype to single nucleotide changes. Here we explore variation on an intermediate scale--particularly insertions, deletions and inversions affecting from a few thousand to a few million base pairs. We employed a clone-based method to interrogate this intermediate structural variation in eight individuals of diverse geographic ancestry. Our analysis provides a comprehensive overview of the normal pattern of structural variation present in these genomes, refining the location of 1,695 structural variants. We find that 50% were seen in more than one individual and that nearly half lay outside regions of the genome previously described as structurally variant. We discover 525 new insertion sequences that are not present in the human reference genome and show that many of these are variable in copy number between individuals. Complete sequencing of 261 structural variants reveals considerable locus complexity and provides insights into the different mutational processes that have shaped the human genome. These data provide the first high-resolution sequence map of human structural variation--a standard for genotyping platforms and a prelude to future individual genome sequencing projects.