Capture of hydroxymethylene and its fast disappearance through tunnelling

Singlet carbenes exhibit a divalent carbon atom whose valence shell contains only six electrons, four involved in bonding to two other atoms and the remaining two forming a non-bonding electron pair. These features render singlet carbenes so reactive that they were long considered too short-lived for isolation and direct characterization. This view changed when it was found that attaching the divalent carbon atom to substituents that are bulky and/or able to donate electrons produces carbenes that can be isolated and stored. N-heterocyclic carbenes are such compounds now in wide use, for example as ligands in metathesis catalysis. In contrast, oxygen-donor-substituted carbenes are inherently less stable and have been less studied. The pre-eminent case is hydroxymethylene, H-C-OH; although it is the key intermediate in the high-energy chemistry of its tautomer formaldehyde, has been implicated since 1921 in the photocatalytic formation of carbohydrates, and is the parent of alkoxycarbenes that lie at the heart of transition-metal carbene chemistry, all attempts to observe this species or other alkoxycarbenes have failed. However, theoretical considerations indicate that hydroxymethylene should be isolatable. Here we report the synthesis of hydroxymethylene and its capture by matrix isolation. We unexpectedly find that H-C-OH rearranges to formaldehyde with a half-life of only 2 h at 11 K by pure hydrogen tunnelling through a large energy barrier in excess of 30 kcal mol(-1).     

Unfolding Incomplete Data: Guidelines for Unfolding Row-Conditional Rank Order Data with Random Missings

Unfolding creates configurations from preference information. In this paper, it is argued that not all preference information needs to be collected and that good solutions are still obtained, even when more than half of the data is missing. Simulation studies are conducted to compare missing data treatments, sources of missing data, and designs for the specification of missing data. Guidelines are provided and used in actual practice.     

Redox-dependent thiol modifications: implications for the release of extracellular vesicles

Extracellular vesicles (EVs), including microvesicles and exosomes, are emerging as important regulators of homeostasis and pathophysiology. During pro-inflammatory and pro-oxidant conditions, EV release is induced. As EVs released under such conditions often exert pro-inflammatory and procoagulant effects, they may actively promote the pathogenesis of chronic diseases. There is evidence that thiol group-containing antioxidants can prevent EV induction by pro-inflammatory and oxidative stimuli, likely by protecting protein thiols of the EV-secreting cells from oxidation. As the redox state of protein thiols greatly impacts three-dimensional protein structure and, consequently, function, redox modifications of protein thiols may directly modulate EV release in response to changes in the cell’s redox environment. In this review article, we discuss targets of redox-dependent thiol modifications that are known or expected to be involved in the regulation of EV release, namely redox-sensitive calcium channels, N-ethylmaleimide sensitive factor, protein disulfide isomerase, phospholipid flippases, actin filaments, calpains and cell surface-exposed thiols. Thiol protection is proposed as a strategy for preventing detrimental changes in EV signaling in response to inflammation and oxidative stress. Identification of the thiol-containing proteins that modulate EV release in pro-oxidant environments could provide a rationale for broad application of thiol group-containing antioxidants in chronic inflammatory diseases.     

Genomic and metabolic prediction of complex heterotic traits in hybrid maize

Maize is both an exciting model organism in plant genetics and also the most important crop worldwide for food, animal feed and bioenergy production. Recent genome-wide association and metabolic profiling studies aimed to resolve quantitative traits to their causal genetic loci and key metabolic regulators. Here we present a complementary approach that exploits large-scale genomic and metabolic information to predict complex, highly polygenic traits in hybrid testcrosses. We crossed 285 diverse Dent inbred lines from worldwide sources with two testers and predicted their combining abilities for seven biomass- and bioenergy-related traits using 56,110 SNPs and 130 metabolites. Whole-genome and metabolic prediction models were built by fitting effects for all SNPs or metabolites. Prediction accuracies ranged from 0.72 to 0.81 for SNPs and from 0.60 to 0.80 for metabolites, allowing a reliable screening of large collections of diverse inbred lines for their potential to create superior hybrids.     

Seven prostate cancer susceptibility loci identified by a multi-stage genome-wide association study

Prostate cancer (PrCa) is the most frequently diagnosed male cancer in developed countries. We conducted a multi-stage genome-wide association study for PrCa and previously reported the results of the first two stages, which identified 16 PrCa susceptibility loci. We report here the results of stage 3, in which we evaluated 1,536 SNPs in 4,574 individuals with prostate cancer (cases) and 4,164 controls. We followed up ten new association signals through genotyping in 51,311 samples in 30 studies from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium. In addition to replicating previously reported loci, we identified seven new prostate cancer susceptibility loci on chromosomes 2p11, 3q23, 3q26, 5p12, 6p21, 12q13 and Xq12 (P = 4.0 × 10(-8) to P = 2.7 × 10(-24)). We also identified a SNP in TERT more strongly associated with PrCa than that previously reported. More than 40 PrCa susceptibility loci, explaining ～25% of the familial risk in this disease, have now been identified.