Ionic Channels as Natural Nanodevices

Ion channels are proteins with a hole down their middle important in a wide range of biological functions yet simple enough to be analyzed as devices in the engineering tradition.     

Crystal structure of TNF-alpha mutant R31D with greater affinity for receptor R1 compared with R2

Crystal structures have been determined of recombinant human tumor necrosis factor-alpha (TNF-alpha) and its R31D mutant that preferentially binds to TNF receptor R1 with more than seven times the relative affinity of binding to receptor R2. Crystals of the wild-type TNF were of space group P4(1)2(1)2 and had unit cell dimensions of a = b = 94.7 and c = 117.4 A. Refinement of the structure gave an R-factor of 22.3% at 2.5 A resolution. The crystals of TNF R31D mutant diffracted to 2.3 A resolution, and were of identical space group to the wild type with unit cell dimensions of a = b = 95.4 and c = 116.2 A, and the structure was refined to an R-factor of 21.8%. The trimer structures of the wild-type and mutant TNF were similar with a root mean square (r.m.s.) deviation of 0.56 A for Calpha atoms; however, the subunits within each trimer were more variable with an average r.m.s. deviation of 1.00 A on Calpha atoms for pairwise comparison of subunits. Model complexes of TNF with receptors R1 and R2 have been used to predict TNF-receptor interactions. Arg31 in all three subunits of wild-type TNF is predicted to form an ionic interaction with the equivalent glutamic acid in both receptors R1 and R2. Asp31 of the TNF R31D mutant is predicted to interact differently with the two receptors. The side chain of Asp31 in two subunits of the TNF mutant is predicted to form hydrogen bond interactions with Ser59 or Cys70 of R1, while it has no predicted interactions with R2. The loss of three strong ionic interactions of Arg31 and the electrostatic repulsion of Asp31 with Glu in the receptors is consistent with the reduced binding of the R31D mutant to both receptors relative to wild-type TNF. The replacement of these ionic interactions by two weaker hydrogen bond interactions between Asp31 of the R31D mutant and R1, compared with no interactions with R2, is in agreement with the observed preferential binding of the R31D mutant to R1 over R2. Analysis of the structure and function of receptor-discriminating mutants of TNF will help understand the biological role of TNF and facilitate its use as an antitumor agent.      

The developmental trajectories of attention focusing, attentional and behavioral persistence, and externalizing problems during school-age years.

The developmental trajectories of attention focusing (by parents' and teachers' reports) and attentional and behavioral persistence (observed during a laboratory task)--2 indexes of effortful control--and externalizing problems from ages 5 to 10 years were examined for 356 children combined from a pair of 3-wave (2 years apart) longitudinal studies. The authors identified clusters of children with distinct trajectories for these variables and examined the links between the effortful control trajectories and the externalizing problem trajectories. Although attention focusing remained relatively stable, attentional and behavioral persistence continued to show mean-level changes (especially among the children with lower levels of persistence). Children with high and stable trajectories of effortful control tended to exhibit low and stable trajectories of externalizing problems, whereas those with lower and/or less stable trajectories of effortful control showed more elevated and/or fluctuating trajectories of externalizing problems. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sex differences in empathy and related capacities.

Reviews the literature on sex differences in empathy (defined as vicarious affective responding to the emotional state of another) and related capacities (affective role taking and decoding of nonverbal cues). The literature is discussed according to method used to assess empathy and affective role taking. Where appropriate, meta-analyses were also computed. In general, sex differences in empathy were found to be a function of the methods used to assess empathy. There was a large sex difference favoring women when the measure of empathy was self-report scales; moderate differences (favoring females) were found for reflexive crying and self-report measures in laboratory situations; and no sex differences were evident when the measure of empathy was either physiological or unobtrusive observations of nonverbal reactions to another's emotional state. Moreover, few sex differences were found for children's affective role taking and decoding abilities. (156 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Photoaffinity labeling of the human erythrocyte nucleoside transporter by N6-(p-Azidobenzyl)adenosine and nitrobenzylthioinosine. Evidence that the transporter is a band 4.5 polypeptide

N6-(p-Azidobenzyl)adenosine (ABA) and nitrobenzylthioinosine (NBMPR) were employed as covalent probes of the nucleoside transport mechanism in human erythrocytes. NBMPR, a potent inhibitor of nucleoside transport, binds tightly (KD 0.3-1 nM) to specific sites on nucleoside transporter elements. ABA, a less potent inhibitor of uridine influx, competitively inhibited NBMPR binding (Ki 15 nM). [3H]ABA was bound tightly (KD 13.4 nM) but reversibly to sites on erythrocytes which appeared to be those which bind NBMPR. ABA binding was inhibited by uridine and adenosine. Irradiation with UV light caused site-bound [3H]ABA on erythrocyte membranes to become covalently bound and, similarly, photoactivation resulted in covalent attachment of membrane-bound [3H]NBMPR. In the presence of dithiothreitol, a free radical scavenger, photoactivation of the site-bound 3H-ligand on membranes depleted of extrinsic membrane proteins resulted in selective incorporation of 3H into band 4.5 of the membrane polypeptides which were resolved on sodium dodecyl sulfate-polyacrylamide gel electropherograms. This result, when considered with previous findings, indicates that the NBMPR-binding component of the nucleoside transport mechanism (or the entire mechanism, if the NBMPR site is an integral part) is a band 4.5 polypeptide.     

Lung mechanics in sitting and horizontal body positions

We measured lung compliance, pulmonary flow-resistance, and expiratory reserve volume (ERV) in ten healthy young adults in sitting, supine, and lateral positions. Average lung compliance was 0.21 in sitting, 0.19 in lateral and 0.16 L.cm H2O-1 in supine positions. The change was significant (p less than 0.01) between sitting and supine position. Flow-resistance increased from 1.78 in sitting to 2.5 cm H2O.L-1.s (p less than 0.001) in lateral positions, and did not increase further in the supine posture in spite of a 35 percent decrease in ERV (p less than 0.001). Since it is known that lower airways resistance increases with decreasing lung volume, the lack of change in flow-resistance when shifting from lateral to supine posture suggests that upper airways flow-resistance (larynx and oropharynx) is greater in the lateral decubitus than in the supine positions. The decrease of lung compliance in horizontal postures probably reflects increased pulmonary blood volume and small airways closure.     

An outline theory of surface morphology development during radiation enhanced reactant gas erosion

A phenomenological model of erosion of solids by reactive gases enhanced by simultaneous surface irradiation (e.g. by ions) is developed. The model is based upon the assumption that the radiation generates activated atomic states which can be preferentially removed, with accompanying atomic erosion, at a rate proportional to the product of the surface activated state density and reactant gas flux. This model allows deduction of erosion velocity as a function of surface orientation and it is shown how knowledge of this function can be used to predict the evolution of surface morphology.