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This study shows that metallic glasses can be rejuvenated (taken to higher energy states with more plasticity) by thermally cycling them at relatively low temperatures (well below the glass transition temperature); this is attributed to the effect of intrinsic structural inhomogeneities in the glassy state, which translate into localized internal strains as the temperature is cycled and the different regions expand and contract by different amounts. A metallic glass rejuvenated As a glassy system slowly relaxes towards equilibrium, it is said to 'age', with corresponding changes in many of its material properties. Push the system back away from equilibrium via the injection of energy — for example by heating or mechanically stressing it — and its youthful character can be recovered. Now Sergey Ketov et al . find that such rejuvenation can be achieved under much more benign conditions. By simply thermally cycling the glass (or, in this instance, the metallic glass) at a temperature well below the glass-transition temperature, a surprisingly large degree of rejuvenation can be achieved. The authors attribute this to the effect of intrinsic structural heterogeneities in the glassy state, which translate into localized internal strains as the temperature cycles and the different regions expand and contract by different amounts. When a spatially uniform temperature change is imposed on a solid with more than one phase, or on a polycrystal of a single, non-cubic phase (showing anisotropic expansion–contraction), the resulting thermal strain is inhomogeneous (non-affine). Thermal cycling induces internal stresses, leading to structural and property changes that are usually deleterious. Glasses are the solids that form on cooling a liquid if crystallization is avoided—they might be considered the ultimate, uniform solids, without the microstructural features and defects associated with polycrystals. Here we explore the effects of cryogenic thermal cycling on glasses, specifically metallic glasses. We show that, contrary to the null effect expected from uniformity, thermal cycling induces rejuvenation, reaching less relaxed states of higher energy. We interpret these findings in the context that the dynamics in liquids become heterogeneous on cooling towards the glass transition 1 , and that there may be consequent heterogeneities in the resulting glasses. For example, the vibrational dynamics of glassy silica at long wavelengths are those of an elastic continuum, but at wavelengths less than approximately three nanometres the vibrational dynamics are similar to those of a polycrystal with anisotropic grains 2 . Thermal cycling of metallic glasses is easily applied, and gives improvements in compressive plasticity. The fact that such effects can be achieved is attributed to intrinsic non-uniformity of the glass structure, giving a non-uniform coefficient of thermal expansion. While metallic glasses may be particularly suitable for thermal cycling, the non-affine nature of strains in glasses in general deserves further study, whether they are induced by applied stresses or by temperature change.

\"Living Marine Resources of Kuwait, Eastern Saudi Arabia, Bahrain, Qatar, and the United Arab Emirates\" is a definitive taxonomic and ecological guide to the marine life of the Persian (Arabian) Gulf. Published primarily as a technical resource for the Food and Agriculture Organization (FAO), the work provides an exhaustive inventory of the fish, crustaceans, mollusks, and sea turtles inhabiting the shallow, hypersaline waters of the southern and western Gulf. Authored by Kent E. Carpenter and his colleagues, the manual serves as a critical tool for species identification, fisheries management, and biodiversity conservation in one of the most thermally extreme marine environments on Earth.

The single-stranded DNA cytosine-to-uracil deaminase APOBEC3B is an antiviral protein implicated in cancer. However, its substrates in cells are not fully delineated. Here APOBEC3B proteomics reveal interactions with a surprising number of R-loop factors. Biochemical experiments show APOBEC3B binding to R-loops in cells and in vitro. Genetic experiments demonstrate R-loop increases in cells lacking APOBEC3B and decreases in cells overexpressing APOBEC3B. Genome-wide analyses show major changes in the overall landscape of physiological and stimulus-induced R-loops with thousands of differentially altered regions, as well as binding of APOBEC3B to many of these sites. APOBEC3 mutagenesis impacts genes overexpressed in tumors and splice factor mutant tumors preferentially, and APOBEC3-attributed kataegis are enriched in RTCW motifs consistent with APOBEC3B deamination. Taken together with the fact that APOBEC3B binds single-stranded DNA and RNA and preferentially deaminates DNA, these results support a mechanism in which APOBEC3B regulates R-loops and contributes to R-loop mutagenesis in cancer. APOBEC3B interacts with R-loops and helps mediate their resolution in a deamination-dependent way. This association also renders R-loops susceptible to enhanced APOBEC3B-dependent mutagenesis.

\"This collection of 171 letters, most never before published, finally makes the fascinating Shaw/Murray correspondence available. With explanatory headnotes and footnotes by Charles A. Carpenter, Bernard Shaw and Gilbert Murray offers insight into an unusual literary and political friendship.\"-- Publisher description.

Crystal structures of human APOBEC3A and a chimera of APOBEC3B and APOBEC3A bound to ssDNA reveal an unanticipated ‘U-shaped’ binding mode and provide insight into target selectivity. APOBEC-catalyzed cytosine-to-uracil deamination of single-stranded DNA (ssDNA) has beneficial functions in immunity and detrimental effects in cancer. APOBEC enzymes have intrinsic dinucleotide specificities that impart hallmark mutation signatures. Although numerous structures have been solved, mechanisms for global ssDNA recognition and local target-sequence selection remain unclear. Here we report crystal structures of human APOBEC3A and a chimera of human APOBEC3B and APOBEC3A bound to ssDNA at 3.1-Å and 1.7-Å resolution, respectively. These structures reveal a U-shaped DNA conformation, with the specificity-conferring −1 thymine flipped out and the target cytosine inserted deep into the zinc-coordinating active site pocket. The −1 thymine base fits into a groove between flexible loops and makes direct hydrogen bonds with the protein, accounting for the strong 5′-TC preference. These findings explain both conserved and unique properties among APOBEC family members, and they provide a basis for the rational design of inhibitors to impede the evolvability of viruses and tumors.

A suboptimal early-life environment, due to poor nutrition or stress during pregnancy, can influence lifelong phenotypes in the progeny. Epigenetic factors are thought to be key mediators of these effects. We show that protein restriction in mice from conception until weaning induces a linear correlation between growth restriction and DNA methylation at ribosomal DNA (rDNA). This epigenetic response remains into adulthood and is restricted to rDNA copies associated with a specific genetic variant within the promoter. Related effects are also found in models of maternal high-fat or obesogenic diets. Our work identifies environmentally induced epigenetic dynamics that are dependent on underlying genetic variation and establishes rDNA as a genomic target of nutritional insults.

Many material properties such as superconductivity, magnetoresistance or magnetoelectricity emerge from the non-linear interactions of spins and lattice/phonons. Hence, an in-depth understanding of spin–phonon coupling is at the heart of these properties. While most examples deal with one magnetic lattice only, the simultaneous presence of multiple magnetic orderings yield potentially unknown properties. We demonstrate a strong spin–phonon coupling in SmFeO 3 that emerges from the interaction of both, iron and samarium spins. We probe this coupling as a remarkably large shift of phonon frequencies and the appearance of new phonons. The spin–phonon coupling is absent for the magnetic ordering of iron alone but emerges with the additional ordering of the samarium spins. Intriguingly, this ordering is not spontaneous but induced by the iron magnetism. Our findings show an emergent phenomenon from the non-linear interaction by multiple orders, which do not need to occur spontaneously. This allows for a conceptually different approach in the search for yet unknown properties. Typically, magnetic phenomena result from the spontaneous order of the sublattices. Here, the cross-talk of two magnetic ions gives rise to an intrinsic, yet non-spontaneous ordering and manifests as emergent strong spin–phonon coupling in SmFeO 3 .

The DNA cytosine deaminase APOBEC3B is shown to be overexpressed and highly active in most breast cancers; deamination by APOBEC3B could serve as an endogenous, continual source of DNA damage leading to mutations, including C-to-T transitions and other aberrations seen in many breast tumours. Deamination-induced cancer mutations The profile of C-to-T transition mutations in breast cancer suggests a non-spontaneous origin. This paper shows that some of these mutations may arise from the upregulation of a cytosine deaminase, APOBEC3B (A3B), in such cancer cells. Deamination catalysed by A3B could serve as an endogenous, continual source of DNA damage that leads to mutations and DNA fragmentation, whereas inactivation of TP53 , which is frequently observed in cells overexpressing A3B, would prevent the elimination of such damaged cells by apoptosis. A3B may be a useful marker for breast cancer and also a candidate for targeted intervention, especially given its non-essential nature. Several mutations are required for cancer development, and genome sequencing has revealed that many cancers, including breast cancer, have somatic mutation spectra dominated by C-to-T transitions 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 . Most of these mutations occur at hydrolytically disfavoured 10 non-methylated cytosines throughout the genome, and are sometimes clustered 8 . Here we show that the DNA cytosine deaminase APOBEC3B is a probable source of these mutations. APOBEC3B messenger RNA is upregulated in most primary breast tumours and breast cancer cell lines. Tumours that express high levels of APOBEC3B have twice as many mutations as those that express low levels and are more likely to have mutations in TP53 . Endogenous APOBEC3B protein is predominantly nuclear and the only detectable source of DNA C-to-U editing activity in breast cancer cell-line extracts. Knockdown experiments show that endogenous APOBEC3B correlates with increased levels of genomic uracil, increased mutation frequencies, and C-to-T transitions. Furthermore, induced APOBEC3B overexpression causes cell cycle deviations, cell death, DNA fragmentation, γ-H2AX accumulation and C-to-T mutations. Our data suggest a model in which APOBEC3B-catalysed deamination provides a chronic source of DNA damage in breast cancers that could select TP53 inactivation and explain how some tumours evolve rapidly and manifest heterogeneity.

Mineral dust particles from wind-blown soils are known to act as effective ice nucleating particles in the atmosphere and are thought to play an important role in the glaciation of mixed phase clouds. Recent work suggests that feldspars are the most efficient nucleators of the minerals commonly present in atmospheric mineral dust. However, the feldspar group of minerals is complex, encompassing a range of chemical compositions and crystal structures. To further investigate the ice-nucleating properties of the feldspar group we measured the ice nucleation activities of 15 characterized feldspar samples. We show that alkali feldspars, in particular the potassium feldspars, generally nucleate ice more efficiently than feldspars in the plagioclase series which contain significant amounts of calcium. We also find that there is variability in ice nucleating ability within these groups. While five out of six potassium-rich feldspars have a similar ice nucleating ability, one potassium rich feldspar sample and one sodium-rich feldspar sample were significantly more active. The hyper-active Na-feldspar was found to lose activity with time suspended in water with a decrease in mean freezing temperature of about 16 °C over 16 months; the mean freezing temperature of the hyper-active K-feldspar decreased by 2 °C over 16 months, whereas the \"standard\" K-feldspar did not change activity within the uncertainty of the experiment. These results, in combination with a review of the available literature data, are consistent with the previous findings that potassium feldspars are important components of arid or fertile soil dusts for ice nucleation. However, we also show that there is the possibility that some alkali feldspars may have enhanced ice nucleating abilities, which could have implications for prediction of ice nucleating particle concentrations in the atmosphere.