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In the past year, several groups have observed evidence for long-range spin-triplet supercurrent in Josephson junctions containing ferromagnetic (F) materials. In our work, the spin-triplet pair correlations are created by non-collinear magnetizations between a central Co/Ru/Co "synthetic antiferromagnet" (SAF) and two outer thin F layers. Here we present data showing that the spin-triplet supercurrent is enhanced up to 20 times after our samples are subject to a large in-plane magnetizing field. This surprising result can be explained if the Co/Ru/Co SAF undergoes a "spin-flop" transition, whereby the two Co layer magnetizations end up perpendicular to the magnetizations of the two thin F layers. Direct experimental evidence for the spin-flop transition comes from scanning electron microscopy with polarization analysis and from spin-polarized neutron reflectometry.

Bile acids (BAs) are a group of important physiological agents for cholesterol metabolism, intestinal nutrient absorption, and biliary secretion of lipids, toxic metabolites, and xenobiotics. Extensive research in the last two decades has unveiled new functions of BAs as signaling molecules and metabolic regulators that modulate hepatic lipid, glucose, and energy homeostasis through the activation of nuclear receptors and G-protein-coupled receptor signaling in gut-liver metabolic axis involving host-gut microbial co-metabolism. Therefore, investigation of serum BA profiles, in healthy human male and female subjects with a wide range of age and body mass index (BMI), will provide important baseline information on the BA physiology as well as metabolic homeostasis among human subjects that are regulated by two sets of genome, host genome, and symbiotic microbiome. Previous reports on age- or gender-related changes on BA profiles in animals and human showed inconsistent results, and the information acquired from various studies was highly fragmentary. Here we profiled the serum BAs in a large population of healthy participants (n = 502) and examined the impact of age, gender, and BMI on serum BA concentrations and compositions using a targeted metabonomics approach with ultraperformance liquid chromatography triple-quadrupole mass spectrometry. We found that the BA profiles were dependent on gender, age, and BMI among study subjects. The total BAs were significantly higher in males than in females (p < 0.05) and higher in obese females than in lean females (p < 0.05). The difference in BA profiles between male and female subjects was decreased at age of 50-70 years, while the difference in BA profiles between lean and obese increased for subjects aged 50-70 years. The study provides a comprehensive understanding of the BA profiles in healthy subjects and highlights the need to take into account age, gender, and BMI differences when investigating pathophysiological changes of BAs resulting from gastrointestinal diseases.

(J.-L.M., S.M.)Meiosis is often described as a special case of cell division since it differs from mitosis in having two nuclear divisions without an intervening S-phase. It will be of great interest to uncover what molecular mechanisms underlie these special features of meiosis. We previously reported that the tardy asynchronous meiosis (tam) mutant of Arabidopsis (Arabidopsis thaliana) is slower in cell cycle progression in male meiosis. Here we report that TAM encodes the A-type cyclin, CYCA1;2. The point mutation in tam replaced a conserved threonine with an isoleucine in the linker region between the a4 and a5 helices of the first cyclin fold. By studying the dynamics of a CYCA1;2-green fluorescent protein fusion protein under the control of the CYCA1;2 promoter, we found that the fusion protein was most abundant at pachytene, but was undetectable from late prophase I until telophase II. Nonetheless, cell cycle progression in tam was delayed in both pachytene and meiosis II. We conclude either that the CYCA1;2 produced in prophase I indirectly regulates meiosis II progression, or that a very low level of CYCA1;2 directly regulates meiosis II progression. Either of these scenarios is a deviation from the typical mode of action of mitotic cyclins in mitosis and meiosis I, in which each nuclear division is coupled with a peak of expression of mitotic cyclins.A hallmark of cell cycle progression in mitosis is that mitotic cyclins oscillate once with each cell cycle; a high level at the G2/M transition or some time into the M-phase is followed by an abrupt decline before exit from M-phase (Nurse, 2002). Meiosis, in contrast to mitosis, consists of two consecutive nuclear divisions without an intervening S-phase for chromosome duplication, defining an M-M phase transition between meiosis I and meiosis II (Kishimoto, 2003). However, at the molecular level, if or how the meiosis I-meiosis II transition differs from the transition between two consecutive mitotic cell cycles remains largely unknown.There are two types of mitotic cyclins: A and B. There is some information about meiotic modulation of the oscillation of B-type cyclins. It has been found that degradation of cyclin B is not required for the meiosis I-meiosis II transition (Taieb et al., 2001). This phenomenon suggests that the meiosis I-meiosis II transition does not likely involve an exit from an earlier M-phase and reentry into a subsequent M-phase, because degradation of mitotic cyclins is required for exit from M-phase in mitosis (Nurse, 2002). In fact, incomplete degradation of cyclin B at the end of meiosis I is essential for preventing the entry into S-phase in meiosis II in animals (Picard et al., 1996;Sakamoto et al., 1998;Iwabuchi et al., 2000;Taieb et al., 2001;Perez et al., 2002). In female meiosis of some animal species that normally undergo an arrest in metaphase II, depletion of cyclin B leads to the absence of the meiosis II spindle, underscoring the importance of new cyclin B synthesis for stabilizing the metaphase II spindle in these sp...

The application of metabolomics in translational research suffers from several technological bottlenecks, such as data reproducibility issues and the lack of standardization of sample profiling procedures. Here, we report an automated high-throughput metabolite array technology that can rapidly and quantitatively determine 324 metabolites including fatty acids, amino acids, organic acids, carbohydrates, and bile acids. Metabolite identification and quantification is achieved using the Targeted Metabolome Batch Quantification (TMBQ) software, the first cross-vendor data processing pipeline. A test of this metabolite array was performed by analyzing serum samples from patients with chronic liver disease (N = 1234). With high detection efficiency and sensitivity in serum, urine, feces, cell lysates, and liver tissue samples and suitable for different mass spectrometry systems, this metabolite array technology holds great potential for biomarker discovery and high throughput clinical testing. Additionally, data generated from such standardized procedures can be used to generate a clinical metabolomics database suitable for precision medicine in next-generation healthcare.

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Mutations that eliminate chloroplast translation in Arabidopsis (Arabidopsis thaliana) result in embryo lethality. The stage of embryo arrest, however, can be influenced by genetic background. To identify genes responsible for improved growth in the absence of chloroplast translation, we examined seedling responses of different Arabidopsis accessions on spectinomycin, an inhibitor of chloroplast translation, and crossed the most tolerant accessions with embryo-defective mutants disrupted in chloroplast ribosomal proteins generated in a sensitive background. The results indicate that tolerance is mediated by ACC2, a duplicated nuclear gene that targets homomeric acetyl-coenzyme A carboxylase to plastids, where the multidomain protein can participate in fatty acid biosynthesis. In the presence of functional ACC2, tolerance is enhanced by a second locus that maps to chromosome 5 and heightened by additional genetic modifiers present in the most tolerant accessions. Notably, some of the most sensitive accessions contain nonsense mutations in ACC2, including the "Nossen" line used to generate several of the mutants studied here. Functional ACC2 protein is therefore not required for survival in natural environments, where heteromeric acetyl-coenzyme A carboxylase encoded in part by the chloroplast genome can function instead. This work highlights an interesting example of a tandem gene duplication in Arabidopsis, helps to explain the range of embryo phenotypes found in Arabidopsis mutants disrupted in essential chloroplast functions, addresses the nature of essential proteins encoded by the chloroplast genome, and underscores the value of using natural variation to study the relationship between chloroplast translation, plant metabolism, protein import, and plant development.Embryo development in Arabidopsis (Arabidopsis thaliana) requires the coordinated expression of a large number of essential genes (Muralla et al., 2011). Recessive mutations that disrupt these nuclear genes result in an embryodefective (emb) mutant phenotype (Meinke, 2013). Many EMB genes of Arabidopsis encode chloroplast-localized proteins involved in basic metabolism, protein import, and chloroplast gene expression (Hsu et al., 2010;Bryant et al., 2011;Savage et al., 2013). Functional plastids are therefore required for embryo development in Arabidopsis. Mutations that disrupt photosynthesis alone interfere with embryo and seedling pigmentation, not embryo development. Multiple examples of EMB genes that encode chloroplast-localized aminoacyl-tRNA synthetases, RNA-binding proteins, translation factors, and ribosomal proteins have been described in the literature (Berg et al., 2005;Bryant et al., 2011;Muralla et al., 2011;Romani et al., 2012;Tiller and Bock, 2014). Translation of some chloroplast-encoded mRNAs is therefore essential for seed development. This raises a basic question: which chloroplast genes are required? In this report, we used natural variation and genetic analysis to evaluate the model (Bryant et al., 2011) that a single chloro...