Nucleosome positioning stability is a modulator of germline mutation rate variation across the human genome

Nucleosome organization has been suggested to affect local mutation rates in the genome. However, the lack of de novo mutation and high-resolution nucleosome data has limited the investigation of this hypothesis. Additionally, analyses using indirect mutation rate measurements have yielded contradictory and potentially confounding results. Here, we combine data on >300,000 human de novo mutations with high-resolution nucleosome maps and find substantially elevated mutation rates around translationally stable (\u27strong\u27) nucleosomes. We show that the mutational mechanisms affected by strong nucleosomes are low-fidelity replication, insufficient mismatch repair and increased double-strand breaks. Strong nucleosomes preferentially locate within young SINE/LINE transposons, suggesting that when subject to increased mutation rates, transposons are then more rapidly inactivated. Depletion of strong nucleosomes in older transposons suggests frequent positioning changes during evolution. The findings have important implications for human genetics and genome evolution

Classical Heisenberg model of magnetic molecular ring clusters: Accurate approximants for correlation functions and susceptibility

The article of record as published may be found at https://doi.org/10.1063/1.476144We show that the measured magnetic susceptibility of molecular ring clusters can be accurately reproduced, for all but low temperatures T, by a classical Heisenberg model of N identical spins S on a ring that interact with isotropic nearest-neighbor interactions. While exact expressions for the two-spin correlation function, C{sub N}(n,T), and the zero-field magnetic susceptibility, {chi}{sub N}(T), are known for the classical Heisenberg ring, their evaluation involves summing infinite series of modified spherical Bessel functions. By contrast, the formula C{sub N}(n,T)=(u{sup n}+u{sup N{minus}n})/(1+u{sup N}), where u(K)=cothK{minus}K{sup {minus}1} is the Langevin function and K=JS(S+1)/(k{sub B}T) is the nearest-neighbor dimensionless coupling constant, provides an excellent approximation if N{ge}6 for the regime {vert_bar}K{vert_bar}{lt}3. This choice of approximant combines the expected exponential decay of correlations for increasing yet small values of n, with the cyclic boundary condition for a finite ring, C{sub N}(n,T)=C{sub N}(N{minus}n,T). By way of illustration, we show that, for T{gt}50K, the associated approximant for the susceptibility derived from the approximate correlation function is virtually indistinguishable from both the exact theoretical susceptibility and the experimental data for the {open_quotes}ferric wheel{close_quotes} molecular cluster ([Fe(OCH{sub 3}){sub 2}(O{sub 2}CCH{sub 2}Cl)]{sub 10}), which contains N=10 interacting Fe{sup 3+} ions, each of spin S=5/2, that are symmetrically positioned in a nearly planar ring. {copyright} {ital 1998 American Institute of Physics.

clipplotr - a comparative visualisation and analysis tool for CLIP data

CLIP technologies are now widely used to study RNA-protein interactions and many datasets are now publicly available. An important first step in CLIP data exploration is the visual inspection and assessment of processed genomic data on selected genes or regions and performing comparisons: either across conditions within a particular project, or incorporating publicly available data. However, the output files produced by data processing pipelines or preprocessed files available to download from data repositories are often not suitable for direct comparison and usually need further processing. Furthermore, to derive biological insight it is usually necessary to visualise CLIP signal alongside other data such as annotations, or orthogonal functional genomic data (e.g. RNA-seq). We have developed a simple, but powerful, command-line tool: clipplotr, which facilitates these visual comparative and integrative analyses with normalisation and smoothing options for CLIP data and the ability to show these alongside reference annotation tracks and functional genomic data. These data can be supplied as input to clipplotr in a range of file formats, which will output a publication quality figure. It is written in R and can both run on a laptop computer independently, or be integrated into computational workflows on a high-performance cluster. Releases, source code and documentation are freely available at: https://github.com/ulelab/clipplotr

Long-term weight maintenance and cardiovascular risk factors are not different following weight loss on carbohydrate-restricted diets high in either monounsaturated fat or protein in obese hyperinsulinaemic men and women

The aim of this study was to determine after 52 weeks whether advice to follow a lower carbohydrate diet, either high in monounsaturated fat or low fat, high in protein had differential effects in a free-living community setting. Following weight loss on either a high monounsaturated fat, standard protein (HMF; 50 % fat, 20 % protein (67 g/d), 30 % carbohydrate) or a high protein, moderate fat (HP) (40 % protein (136 g/d), 30 % fat, 30 % carbohydrate) energy-restricted diet (6000 kJ/d) subjects were asked to maintain the same dietary pattern without intensive dietary counselling for the following 36 weeks. Overall weight loss was 6·2 (sd 7·3) kg (P < 0·01 for time with no diet effect, 7·6 (sd 8·1) kg, HMF v. 4·8 (sd 6·6) kg, HP). In a multivariate regression model predictors of weight loss at the end of the study were sex, age and reported percentage energy from protein (R2 0·22, P < 0·05 for the whole model). Fasting plasma insulin decreased (P < 0·01, with no difference between diets), 13·9 (sd 4·6) to 10·2 (sd 5·2) mIU/l, but fasting plasma glucose was not reduced. Neither total cholesterol nor LDL-cholesterol were different but HDL was higher, 1·19 (sd 0·26) v. 1·04 (sd 0·29) (P < 0·001 for time, no diet effect), while TAG was lower, 1·87 (sd 1·23) v. 2·22 (sd 1·15) mmol/l (P < 0·05 for time, no diet effect). C-reactive protein decreased (3·97 (sd 2·84) to 2·43 (sd 2·29) mg/l, P < 0·01). Food records showed that compliance to the prescribed dietary patterns was poor. After 1 year there remained a clinically significant weight loss and improvement in cardiovascular risk factors with no adverse effects of a high monounsaturated fat diet.Jennifer B. Keogh, Natalie D. Luscombe-Marsh, Manny Noakes, Gary A. Wittert and Peter M. Clifto

Quantum point contact due to Fermi-level pinning and doping profiles in semiconductor nanocolumns

We show that nanoscale doping profiles inside a nanocolumn in combination with Fermi-level pinning at the surface give rise to the formation of a saddle-point in the potential profile. Consequently, the lateral confinement inside the channel varies along the transport direction, yielding an embedded quantum point contact. An analytical estimation of the quantization energies will be given

Ligand Decomposition during Nanoparticle Synthesis: Influence of Ligand Structure and Precursor Selection

Aliphatic amine and carboxylic acid ligands are widely used as organic solvents during the bottom-up synthesis of inorganic nanoparticles (NPs). Although the ligands’ ability to alter final NP properties has been widely studied, side reactivity of these ligands is emerging as an important mechanism to consider. In this work, we study the thermal decomposition of common ligands with varying functional groups (amines and carboxylic acids) and bond saturations (from saturated to polyunsaturated). Here, we investigate how these ligand properties influence decomposition in the absence and presence of precursors used in NP synthesis. We show that during the synthesis of inorganic chalcogenide NPs (Cu2ZnSnS4, CuxS, and SnSx) with metal acetylacetonate precursors and elemental sulfur, the ligand pyrolyzes, producing alkylated graphitic species. Additionally, there was less to no ligand decomposition observed during the sulfur-free synthesis of ZnO and CuO with metal acetylacetonate precursors. These results will help guide ligand selection for NP syntheses and improve reaction purity, an important factor in many applications.journal articl