The Tobacco-Related Behavioral Risks of a Nationally Representative Sample of Adolescents

The study\u27s purpose was to determine which factors were the strongest predictors of tobacco smoking behaviors among U.S. adolescents. The population included a nationally representative sample of 6,504 adolescents residing in the U.S. Data were collected in respondents \u27homes using trained interviewers. Weighted population estimates showed that over half (55.6%) of adolescents had ever tried smoking, nearly half of whom (48.2%) reported regular smoking. Those whose closest friends smoked were twice as likely to ever smoke (OR = 2.24, p\u3c.001), twice as likely to be a regular smoker (OK = 2.28, p \u3c.OO1), and more likely (b = 5.15p \u3c.OO1) to have smoked daily than those whose friends do not smoke. Results show the very strong influence of friendships on tobacco initiation and continuance among this national sample of adolescents. Recommendations for primary and secondary prevention are noted

A physically motivated analytical expression for the temperature dependence of the zero-field splitting of the nitrogen-vacancy center in diamond

The temperature dependence of the zero-field splitting (ZFS) between the $|m_{s}=0\rangle$ and $|m_{s}=\pm 1\rangle$ levels of the nitrogen-vacancy (NV) center's electronic ground-state spin triplet can be used as a robust nanoscale thermometer in a broad range of environments. However, despite numerous measurements of this dependence in different temperature ranges, to our knowledge no analytical expression has been put forward that captures the scaling of the ZFS of the NV center across all relevant temperatures. Here we present a simple, analytical, and physically motivated expression for the temperature dependence of the NV center's ZFS that matches all experimental observations, in which the ZFS shifts in proportion to the occupation numbers of two representative phonon modes. In contrast to prior models our expression does not diverge outside the regions of fitting. We show that our model quantitatively matches experimental measurements of the ZFS from 15 to 500 K in single NV centers in ultra-pure bulk diamond, and we compare our model and measurements to prior models and experimental data.Comment: Main text: 7 pages, 4 figures, 1 table, 44 references. Supplemental Material: 12 pages, 5 figures, 2 tables, 23 reference

NewBG: A surrogate corticosteroid-binding globulin with an unprecedentedly high ligand release efficacy

The introduction of ligand-binding sites into proteins and the engineering of molecular allosteric coupling pathways are topical issues in protein design. Here, we show that these issues can be addressed concurrently, using the serpin human α1-antichymotrypsin (ACT) as a model. We have introduced up to 15 amino acid substitutions into ACT, converting it into a surrogate corticosteroid-binding globulin (CBG), thereby creating a new binding globulin (NewBG). Human CBG and ACT share 46% sequence identity, and CBG served as the blue-print for our design, which was guided by side-chain-packing calculations, ITC measurements and crystal structure determinations. Upon transfer of ligand-interacting residues from CBG to ACT and mutation of specific second shell residues, a NewBG variant was obtained, which binds cortisol with 1.5 µM affinity. This novel serpin (NewBG-III) binds cortisol with a 33-fold lower affinity than CBG, but shares a similar ligand-binding profile and binding mode when probed with different steroid ligands and site-directed mutagenesis. An additional substitution, i.e. A349R, created NewBG-III-allo, which introduced an allosteric coupling between ligand binding and the serpin-like S-to-R transition in ACT. In NewBG-III-allo, the proteinase-triggered S-to-R transition leads to a greater than 200-fold reduction in ligand affinity, and crystal structures suggest that this is mediated by the L55V and A349R substitutions. This reduction significantly exceeds the 10-fold reduction in binding affinity observed in human CBG

Design of an allosterically modulated doxycycline and doxorubicin drug binding protein

Significance The design of binding sites for nonnatural ligands into natural proteins is a very topical subject in protein design. This also applies to the manipulation of allosteric coupling pathways with the goal of controlling protein function. Here it is shown that both topics can be addressed concurrently in a single protein. Thus, starting from human α1-antichymotrypsin, two drug-binding proteins were developed. Whereas ligand-binding design enables the binding of either the antibiotic doxycycline or the anticancer compound doxorubicin, the reengineering of an existing allosteric coupling mechanism enables the release of the bound ligands on occurrence of a proteinase trigger signal. It is proposed that such binding proteins can be further developed into drug-specific delivery shuttles.</jats:p

Corticosteroid-binding globulin: structure-function implications from species differences.

Corticosteroid-binding globulin (CBG) transports glucocorticoids and progesterone in the blood and thereby modulates the tissue availability of these hormones. As a member of the serine protease inhibitor (SERPIN) family, CBG displays a reactive center loop (RCL) that is targeted by proteinases. Cleavage of the RCL is thought to trigger a SERPIN-typical stressed-to-relaxed (S-to-R) transition that leads to marked structural rearrangements and a reduced steroid-binding affinity. To characterize structure-function relationships in CBG we studied various conformational states of E. coli-produced rat and human CBG. In the 2.5 Å crystal structure of human CBG in complex with progesterone, the RCL is cleaved at a novel site that differs from the known human neutrophil elastase recognition site. Although the cleaved RCL segment is five residues longer than anticipated, it becomes an integral part of β-sheet A as a result of the S-to-R transition. The atomic interactions observed between progesterone and CBG explain the lower affinity of progesterone in comparison to corticosteroids. Surprisingly, CD measurements in combination with thermal unfolding experiments show that rat CBG fails to undergo an S-to-R transition upon proteolytic cleavage of the RCL hinting that the S-to-R transition observed in human CBG is not a prerequisite for CBG function in rat. This observation cautions against drawing general conclusions about molecular mechanisms by comparing and merging structural data from different species