Letter to the Editor Published in the Christian Intelligencer

A letter of this date to the editor was published December 8, 1859 in The Christian Intelligencer endorsed the Holland Academy. The writers are professors at the New Brunswick Theological Seminary. They conclude their letter by saying, In closing, the undersigned declare their strong conviction, that there have been as few errors of judgment in the management of the Holland Academy as could be expected in any business which fallible men managed. The signers are S[amuel] A. Van Vranken, W[illia]m H. Campbell, and S[amuel] M. Woodbridge.https://digitalcommons.hope.edu/vrp_1850s/1159/thumbnail.jp

Protein disulfide-isomerase interacts with a substrate protein at all stages along its folding pathway

In contrast to molecular chaperones that couple protein folding to ATP hydrolysis, protein disulfide-isomerase (PDI) catalyzes protein folding coupled to formation of disulfide bonds (oxidative folding). However, we do not know how PDI distinguishes folded, partly-folded and unfolded protein substrates. As a model intermediate in an oxidative folding pathway, we prepared a two-disulfide mutant of basic pancreatic trypsin inhibitor (BPTI) and showed by NMR that it is partly-folded and highly dynamic. NMR studies show that it binds to PDI at the same site that binds peptide ligands, with rapid binding and dissociation kinetics; surface plasmon resonance shows its interaction with PDI has a Kd of ca. 10−5 M. For comparison, we characterized the interactions of PDI with native BPTI and fully-unfolded BPTI. Interestingly, PDI does bind native BPTI, but binding is quantitatively weaker than with partly-folded and unfolded BPTI. Hence PDI recognizes and binds substrates via permanently or transiently unfolded regions. This is the first study of PDI's interaction with a partly-folded protein, and the first to analyze this folding catalyst's changing interactions with substrates along an oxidative folding pathway. We have identified key features that make PDI an effective catalyst of oxidative protein folding – differential affinity, rapid ligand exchange and conformational flexibility

FAD binding, cobinamide binding and active site communication in the corrin reductase (CobR)

Adenosylcobalamin, the coenzyme form of vitamin B12, is one Nature's most complex coenzyme whose de novo biogenesis proceeds along either an anaerobic or aerobic metabolic pathway. The aerobic synthesis involves reduction of the centrally chelated cobalt metal ion of the corrin ring from Co(II) to Co(I) before adenosylation can take place. A corrin reductase (CobR) enzyme has been identified as the likely agent to catalyse this reduction of the metal ion. Herein, we reveal how Brucella melitensis CobR binds its coenzyme FAD (flavin dinucleotide) and we also show that the enzyme can bind a corrin substrate consistent with its role in reduction of the cobalt of the corrin ring. Stopped-flow kinetics and EPR reveal a mechanistic asymmetry in CobR dimer that provides a potential link between the two electron reduction by NADH to the single electron reduction of Co(II) to Co(I)

Chemical composition of B-type supergiants in the OB8, OB10, OB48, OB78 associations of M31

Absolute and differential chemical abundances are presented for the largest group of massive stars in M31 studied to date. These results were derived from intermediate resolution spectra of seven B-type supergiants, lying within four OB associations covering a galactocentric distance of 5 - 12 kpc. The results are mainly based on an LTE analysis, and we additionally present a full non-LTE, unified model atmosphere analysis of one star (OB78-277) to demonstrate the reliability of the differential LTE technique. A comparison of the stellar oxygen abundance with that of previous nebular results shows that there is an offset of between ~0.15 - 0.4 dex between the two methods which is critically dependent on the empirical calibration adopted for the R23 parameter with [O/H]. However within the typical errors of the stellar and nebular analyses (and given the strength of dependence of the nebular results on the calibration used) the oxygen abundances determined in each method are fairly consistent. We determine the radial oxygen abundance gradient from these stars, and do not detect any systematic gradient across this galactocentric range. We find that the inner regions of M31 are not, as previously thought, very 'metal rich'. Our abundances of C, N, O, Mg, Si, Al, S and Fe in the M31 supergiants are very similar to those of massive stars in the solar neighbourhood.Comment: 15 pages, 9 figures and 9 tables. Submitted to A&A April 200

Solution NMR assignment of the C-terminal domain of human chTOG

The microtubule regulatory protein colonic and hepatic tumor overexpressed gene (chTOG), also known as cytoskeleleton associated protein 5 (CKAP5) plays an important role in organizing the cytoskeleton and in particular in the assembly of k-fibres in mitosis. Recently, we dissected the hitherto poorly understood C-terminus of this protein by discovering two new domains—a cryptic TOG domain (TOG6) and a smaller, helical domain at the very C-terminus. It was shown that the C-terminal domain is important for the interaction with the TACC domain in TACC3 during the assembly of k-fibres in a ternary complex that also includes clathrin. Here we now present the solution NMR assignment of the chTOG C-terminal domain which confirms our earlier prediction that it is mainly made of α-helices. However, the appearance of the 1H–15N HSQC spectrum is indicative of the presence of a considerable amount of unstructured and possibly flexible portions of protein in the domain

Dephasing of Electrons in Mesoscopic Metal Wires

We have extracted the phase coherence time $\tau_{\phi}$ of electronic quasiparticles from the low field magnetoresistance of weakly disordered wires made of silver, copper and gold. In samples fabricated using our purest silver and gold sources, $\tau_{\phi}$ increases as $T^{-2/3}$ when the temperature $T$ is reduced, as predicted by the theory of electron-electron interactions in diffusive wires. In contrast, samples made of a silver source material of lesser purity or of copper exhibit an apparent saturation of $\tau_{\phi}$ starting between 0.1 and 1 K down to our base temperature of 40 mK. By implanting manganese impurities in silver wires, we show that even a minute concentration of magnetic impurities having a small Kondo temperature can lead to a quasi saturation of $\tau_{\phi}$ over a broad temperature range, while the resistance increase expected from the Kondo effect remains hidden by a large background. We also measured the conductance of Aharonov-Bohm rings fabricated using a very pure copper source and found that the amplitude of the $h/e$ conductance oscillations increases strongly with magnetic field. This set of experiments suggests that the frequently observed ``saturation'' of $\tau_{\phi}$ in weakly disordered metallic thin films can be attributed to spin-flip scattering from extremely dilute magnetic impurities, at a level undetectable by other means.Comment: 16 pages, 11 figures, to be published in Physical Review

PDBe: Protein Data Bank in Europe

The Protein Data Bank in Europe (PDBe) (http://www.ebi.ac.uk/pdbe/) is actively working with its Worldwide Protein Data Bank partners to enhance the quality and consistency of the international archive of bio-macromolecular structure data, the Protein Data Bank (PDB). PDBe also works closely with its collaborators at the European Bioinformatics Institute and the scientific community around the world to enhance its databases and services by adding curated and actively maintained derived data to the existing structural data in the PDB. We have developed a new database infrastructure based on the remediated PDB archive data and a specially designed database for storing information on interactions between proteins and bound molecules. The group has developed new services that allow users to carry out simple textual queries or more complex 3D structure-based queries. The newly designed ‘PDBeView Atlas pages’ provide an overview of an individual PDB entry in a user-friendly layout and serve as a starting point to further explore the information available in the PDBe database. PDBe’s active involvement with the X-ray crystallography, Nuclear Magnetic Resonance spectroscopy and cryo-Electron Microscopy communities have resulted in improved tools for structure deposition and analysis

Kondo Effect on Mesoscopic Scale (Review)

Following the discovery of the Kondo effect the bulk transport and magnetic behavior of the dilute magnetic alloys have been successfully described. In the last fifteen years new directions have been developed as the study of the systems of reduced dimensions and the artificial atoms so called quantum dots. In this review the first subject is reviewed starting with the scanning tunneling microscope (STM) study of a single magnetic impurity. The next subject is the reduction of the amplitude of the Kondo effect in samples of reduced dimension which was explained by the surface magnetic anisotropy which blocks the motion of the integer spin nearby the surface. The electron dephasing and energy relaxation experiments are discussed with the possible explanation including the surface anisotropy, where the situation in cases of integer and half-integer spins is very different. Finally, the present situation of the theory of dynamical structural defects is briefly presented which may lead to two-channel Kondo behavior.Comment: 8 pages, submitted to the JPSJ Special Issue "Kondo effect -- 40 years after the Discovery