Constant linguistic effects in the diffusion of 'be like'

This article examines change in social and linguistic effects on be like usage and acceptability. Results from two studies are presented. The first set of data comes from a trend study with samples of U.K. university undergraduates collected in 1996 and 2006. While the effect of subject person, morphological tense, and quote content is constant in the two samples, the effect of speaker sex decreases. The second study is a judgment experiment with 121 native speakers of U.S. English, examining acceptability of be like in environments biasing direct speech and reported thought readings. The analysis reveals no interaction between age and the reported thought/direct speech contrast, suggesting no support for change in this effect on be like acceptability in apparent time. The two studies therefore converge in suggesting no evidence of change in linguistic constraints on be like as it has diffused into U.K. and U.S. Englishes

Design of a Ruthenium-Cytochrome c Derivative to Measure Electron Transfer to the Initial Acceptor in Cytochrome c Oxidase

A ruthenium-labeled cytochrome c derivative was prepared to meet two design criteria: the ruthenium group must transfer an electron rapidly to the heme group, but not alter the interaction with cytochrome c oxidase. Site-directed mutagenesis was used to replace His39 on the backside of yeast C102T iso-1-cytochrome c with a cysteine residue, and the single sulfhydryl group was labeled with (4-bromomethyl-4' methylbipyridine) (bis-bipyridine)ruthenium(II) to form Ru-39-cytochrome c (cyt c). There is an efficient pathway for electron transfer from the ruthenium group to the heme group of Ru-39-cyt c comprising 13 covalent bonds and one hydrogen bond. Electron transfer from the excited state Ru(II*) to ferric heme c occurred with a rate constant of (6.0 +/- 2.0) x 10(5) s-1, followed by electron transfer from ferrous heme c to Ru(III) with a rate constant of (1.0 +/- 0.2) x 10(6) s-1. Laser excitation of a complex between Ru-39-cyt c and beef cytochrome c oxidase in low ionic strength buffer (5 mM phosphate, pH7) resulted in electron transfer from photoreduced heme c to CuA with a rate constant of (6 +/- 2) x 10(4) s-1, followed by electron transfer from CuA to heme a with a rate constant of (1.8 +/- 0.3) x 10(4) s-1. Increasing the ionic strength to 100 mM leads to bimolecular kinetics as the complex is dissociated. The second-order rate constant is (2.5 +/- 0.4) x 10(7) M-1s-1 at 230 mM ionic strength, nearly the same as that of wild-type iso-1-cytochrome c

Structural basis for receptor activity-modifying protein-dependent selective peptide recognition by a G protein-coupled receptor

Association of receptor activity-modifying proteins (RAMP1-3) with the G protein-coupled receptor (GPCR) calcitonin receptor-like receptor (CLR) enables selective recognition of the peptides calcitonin gene-related peptide (CGRP) and adrenomedullin (AM) that have diverse functions in the cardiovascular and lymphatic systems. How peptides selectively bind GPCR:RAMP complexes is unknown. We report crystal structures of CGRP analog-bound CLR:RAMP1 and AM-bound CLR:RAMP2 extracellular domain heterodimers at 2.5 and 1.8 Å resolutions, respectively. The peptides similarly occupy a shared binding site on CLR with conformations characterized by a β-turn structure near their C termini rather than the α-helical structure common to peptides that bind related GPCRs. The RAMPs augment the binding site with distinct contacts to the variable C-terminal peptide residues and elicit subtly different CLR conformations. The structures and accompanying pharmacology data reveal how a class of accessory membrane proteins modulate ligand binding of a GPCR and may inform drug development targeting CLR:RAMP complexes

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

Reactivity of metal (Znˡˡ, Ruˡˡ)-2,2'-bipyridyl with some bifunctional ligands

1780-1786Complexation of cis-bis(2,2'-bipyridyl)dichlororuthenium(II) dihydrate with carboxaldehyde and carboxylate bearing ligand (4-carboxybenzaldehyde; L¹H) and with bis-acetyl and pyridine containing ligand (2,6-diacetylpyridine; L²) yields [Ru(bpy)₃](PF₆)₂ (bpy = 2,2'-bipyridyl), as the major product in both reactions along with [Ru(bpy)₂(L¹)]PF₆ (1) and [Ru(bpy)₂(L²)](PF₆)₂ (2) as minor products. However, reaction of cis-bis(2,2'-bipyridyl)dichlororuthenium(II) dihydrate with ligand containing bis-triazolo and diimino donor sites [1,4-bis(1,2,4–triazolo-3-imino)benzene; L³H₂] provides [Ru(bpy)₂Cl₂]PF₆ (3) crystals characterized by its single crystal X-ray data along with some unidentified product. Similar to ruthenium bipyridyl, reaction of (2,2'-bipyridyl)dichlorozinc(II) monohydrate with L² has also been carried out which yields [Zn(bpy)₃](PF₆)₂ as a crystalline product along with a polymeric product with the composition [{Zn(bpy)(L²)Cl₂}•DMSO] ո