Ferroelectric ferromagnets are exceedingly rare, fundamentally interesting multiferroic materials that could give rise to new technologies in which the low power and high speed of field-effect electronics are combined with the permanence and routability of voltage-controlled ferromagnetism. Furthermore, the properties of the few compounds that simultaneously exhibit these phenomena are insignificant in comparison with those of useful ferroelectrics or ferromagnets: their spontaneous polarizations or magnetizations are smaller by a factor of 1,000 or more. The same holds for magnetic- or electric-field-induced multiferroics. Owing to the weak properties of single-phase multiferroics, composite and multilayer approaches involving strain-coupled piezoelectric and magnetostrictive components are the closest to application today. Recently, however, a new route to ferroelectric ferromagnets was proposed by which magnetically ordered insulators that are neither ferroelectric nor ferromagnetic are transformed into ferroelectric ferromagnets using a single control parameter, strain. The system targeted, EuTiO(3), was predicted to exhibit strong ferromagnetism (spontaneous magnetization, approximately 7 Bohr magnetons per Eu) and strong ferroelectricity (spontaneous polarization, approximately 10 microC cm(-2)) simultaneously under large biaxial compressive strain. These values are orders of magnitude higher than those of any known ferroelectric ferromagnet and rival the best materials that are solely ferroelectric or ferromagnetic. Hindered by the absence of an appropriate substrate to provide the desired compression we turned to tensile strain. Here we show both experimentally and theoretically the emergence of a multiferroic state under biaxial tension with the unexpected benefit that even lower strains are required, thereby allowing thicker high-quality crystalline films. This realization of a strong ferromagnetic ferroelectric points the way to high-temperature manifestations of this spin-lattice coupling mechanism. Our work demonstrates that a single experimental parameter, strain, simultaneously controls multiple order parameters and is a viable alternative tuning parameter to composition for creating multiferroics.

Epitaxial strain is a proven route to enhancing the properties of complex oxides, however, the details of how the atomic structure accommodates strain are poorly understood due to the difficulty of measuring the oxygen positions in thin films. We present a general methodology for determining the atomic structure of strained oxide films via x-ray diffraction, which we demonstrate using LaNiO3 films. The oxygen octahedral rotations and distortions have been quantified by comparing the intensities of half-order Bragg peaks, arising from the two unit cell periodicity of the octahedral rotations, with the calculated structure factor. Combining ab initio density functional calculations with these experimental results, we determine systematically how strain modifies the atomic structure of this functional oxide.Comment: 23 pages, 11 figure

Mycobacterium tuberculosis is the cause of one of the most deadly diseases of mankind, and despite the availability of effective treatments, tuberculosis (TB) remains a major public health threat. The difficult challenges in treating multiple-drugresistant (MDR) and extensively drug-resistant (XDR) TB and the importance of shortening the duration of treatment to improve patients' compliance make the discovery of new anti-TB drugs imperative (1-5). Attempts to discover new TB drugs and targets via large-scale screening against intact mycobacteria have largely been confined to synthetic compound libraries and to date have yielded only one new clinical TB drug, the diarylquinoline bedaquiline (6, 7). Although very potent, to be of maximum benefit, bedaquiline, a diarylquinoline, and nitroimidazoles (8) require new companion drugs to be used in a multidrug regimen.While the intensive search for antibiotics from soil microorganisms in the mid-20th century yielded several clinically useful TB drugs, the pathogenic nature of M. tuberculosis and its extremely slow growth rate did not allow classical agar diffusion tests and excluded M. tuberculosis from the initial target panel. The discovery of TB drugs of natural origin at that time therefore relied upon the detection of activity against nonmycobacteria in agar diffusion assays followed by bioassay-guided isolation of the active principle, again using nonmycobacteria. Activity against M. tuberculosis was only assessed once the active principle was purified.Because M. tuberculosis is uniquely susceptible to a number of antimicrobial agents, a high-throughput screening (HTS) of actinomycete extracts directly against the virulent H37Rv strain was conducted, and this campaign revealed selective anti-TB peptides produced by a genetically distinct Nonomuraea species, strain MJM5123. Here, we describe the activity profile of ecumicin, its efficacy in infected mice, the identification of its molecular target, and the elucidation of its unusual mechanism of action. MATERIALS AND METHODSHigh-throughput screening. Approximately 7,000 actinomycete cultures isolated from Korea, China, Nepal, the Philippines, Vietnam, Antarctica, and the Arctic Circle and maintained at Myongji University, South Korea, were fermented in 20-ml cultures in glucose-soybean starch (GSS) medium (rich medium), Bennett's medium (normal medium), and dextrinyeast-corn steep liquor (DYC) medium (minimal medium) (see Table S1 in the supplemental material). The mycelia and culture medium supernatants were separated and extracted with methanol and ethyl acetate, respectively. Nine extracts were thus generated from each microbial isolate.

Ferroptosis is an iron-dependent regulated necrosis mediated by lipid peroxidation. Cancer cells survive under metabolic stress conditions by altering lipid metabolism, which may alter their sensitivity to ferroptosis. However, the association between lipid metabolism and ferroptosis is not completely understood. In this study, we found that the expression of elongation of very long-chain fatty acid protein 5 (ELOVL5) and fatty acid desaturase 1 (FADS1) is up-regulated in mesenchymal-type gastric cancer cells (GCs), leading to ferroptosis sensitization. In contrast, these enzymes are silenced by DNA methylation in intestinal-type GCs, rendering cells resistant to ferroptosis. Lipid profiling and isotope tracing analyses revealed that intestinal-type GCs are unable to generate arachidonic acid (AA) and adrenic acid (AdA) from linoleic acid. AA supplementation of intestinal-type GCs restores their sensitivity to ferroptosis. Based on these data, the polyunsaturated fatty acid (PUFA) biosynthesis pathway plays an essential role in ferroptosis; thus, this pathway potentially represents a marker for predicting the efficacy of ferroptosis-mediated cancer therapy.