Numerous descriptions of organic molecules present in the Murchison meteorite have improved our understanding of the early interstellar chemistry that operated at or just before the birth of our solar system. However, all molecular analyses were so far targeted toward selected classes of compounds with a particular emphasis on biologically active components in the context of prebiotic chemistry. Here we demonstrate that a nontargeted ultrahigh-resolution molecular analysis of the solvent-accessible organic fraction of Murchison extracted under mild conditions allows one to extend its indigenous chemical diversity to tens of thousands of different molecular compositions and likely millions of diverse structures. This molecular complexity, which provides hints on heteroatoms chronological assembly, suggests that the extraterrestrial chemodiversity is high compared to terrestrial relevant biologicaland biogeochemical-driven chemical space.Fourier transform ion cyclotron resonance mass spectrometry | interstellar chemistry | nuclear magnetic resonance spectroscopy | organic chondrite | soluble organic matter M urchison chondrite is one of the most studied meteorites and became a reference for extraterrestrial organic chemistry (1). The diversity of organic compounds recorded in Murchison and in other carbon-rich carbonaceous chondrites (1-5) has clearly improved our understanding of the early interstellar chemistry that operated at or just before the birth of our solar system. More than 70% of the Murchison carbon content has been classified as (macromolecular) insoluble organic matter (IOM) of high aromaticity, whereas the soluble fraction contains extensive suites of organic molecules with more than 500 structures identified so far (6). These structures basically resemble known biomolecules, but are considered to result from abiotic synthesis because of peculiar occurrence patterns, racemic mixtures, and stable isotope contents and distributions. Most of the 100+ kg fragments of Murchison were collected shortly after it fell in Australia on September 28, 1969, so that neither of these fresh samples suffered from intensive terrestrial weathering (7).As a whole, Murchison is one of the least-altered chondrites (8), recently reclassified by Rubin et al. (9) as CM2.5, where the aqueous alteration index (2.5 petrologic subtype), based on petrographic and mineralogical properties of the meteorite, indicates that the primary lithology of Murchison had experienced a relatively low and uniform degree of aqueous alteration.Nevertheless, all previous molecular analyses were targeted toward selected classes of compounds with a particular emphasis on amino acids in the context of prebiotic chemistry as potential source of life on earth (10), or on compounds obtained in chemical degradation studies (11) releasing both genuine extractable molecules and reaction products (11-15) often difficult to discern unambiguously.Alternative nontargeted investigations of complex organic systems are now feasible using advanced analytical met...

SummaryA number of bacterial cell processes are confined functional membrane microdomains (FMMs), structurally and functionally similar to lipid rafts of eukaryotic cells. How bacteria organize these intricate platforms and what their biological significance is remain important questions. Using the pathogen methicillin-resistant Staphylococcus aureus (MRSA), we show here that membrane-carotenoid interaction with the scaffold protein flotillin leads to FMM formation, which can be visualized using super-resolution array tomography. These membrane platforms accumulate multimeric protein complexes, for which flotillin facilitates efficient oligomerization. One of these proteins is PBP2a, responsible for penicillin resistance in MRSA. Flotillin mutants are defective in PBP2a oligomerization. Perturbation of FMM assembly using available drugs interferes with PBP2a oligomerization and disables MRSA penicillin resistance in vitro and in vivo, resulting in MRSA infections that are susceptible to penicillin treatment. Our study demonstrates that bacteria possess sophisticated cell organization programs and defines alternative therapies to fight multidrug-resistant pathogens using conventional antibiotics.

The bacterial quorum sensing signals N-acyl-L: -homoserine lactones enable bacterial cells to regulate gene expression depending on population density, in order to undertake collective actions such as the infection of host cells. Only little is known about the molecular ways of plants reacting to these bacterial signals. In this study we show that the contact of Arabidopsis thaliana roots with N-hexanoyl-DL: -homoserine-lactone (C6-HSL) resulted in distinct transcriptional changes in roots and shoots, respectively. Interestingly, unlike most other bacterial signals, C6-HSL influenced only a few defense-related transcripts. Instead, several genes associated with cell growth as well as genes regulated by growth hormones showed changes in their expression after C6-HSL treatment. C6-HSL did not induce plant systemic resistance against Pseudomonas syringae. The inoculation of roots with different types of AHLs led predominantly for short chain N-butyryl-DL: -homoserine lactone and C6-HSL to root elongation. Determination of plant hormone concentrations in root and shoot tissues supported alterations of auxin to cytokinin ratio. Finally, we provide evidence that Arabidopsis takes up bacterial C6-HSL and allows systemic distribution throughout the plant. In sum, the bacterial quorum sensing signal C6-HSL does induce transcriptional changes in Arabidopsis and may contribute to tuning plant growth to the microbial composition of the rhizosphere.

Lipid peroxidation (LPO) is induced by a variety of abiotic and biotic stresses. Although LPO is involved in diverse signaling processes, little is known about the oxidation mechanisms and major lipid targets. A systematic lipidomics analysis of LPO in the interaction of Arabidopsis (Arabidopsis thaliana) with Pseudomonas syringae revealed that LPO is predominantly confined to plastid lipids comprising galactolipid and triacylglyceride species and precedes programmed cell death. Singlet oxygen was identified as the major cause of lipid oxidation under basal conditions, while a 13-lipoxygenase (LOX2) and free radicalcatalyzed lipid oxidation substantially contribute to the increase upon pathogen infection. Analysis of lox2 mutants revealed that LOX2 is essential for enzymatic membrane peroxidation but not for the pathogen-induced free jasmonate production. Despite massive oxidative modification of plastid lipids, levels of nonoxidized lipids dramatically increased after infection. Pathogen infection also induced an accumulation of fragmented lipids. Analysis of mutants defective in 9-lipoxygenases and LOX2 showed that galactolipid fragmentation is independent of LOXs. We provide strong in vivo evidence for a free radicalcatalyzed galactolipid fragmentation mechanism responsible for the formation of the essential biotin precursor pimelic acid as well as of azelaic acid, which was previously postulated to prime the immune response of Arabidopsis. Our results suggest that azelaic acid is a general marker for LPO rather than a general immune signal. The proposed fragmentation mechanism rationalizes the pathogen-induced radical amplification and formation of electrophile signals such as phytoprostanes, malondialdehyde, and hexenal in plastids.Lipid peroxidation (LPO), triggered by lipoxygenases (LOX) and reactive oxygen species (ROS), is a hallmark of plant pathogen responses, both in signal transduction processes and during the execution of programmed cell death. Typically, LOX oxidize free fatty acids in the cytosol or chloroplasts, thereby initiating several oxylipin pathways including the jasmonate and hydroperoxide lyase pathway (Mosblech et al., 2009). Among the ROS typically produced in plant stress responses, only singlet oxygen ( 1 O 2 ) and free radicals are sufficiently reactive to oxidize polyunsaturated fatty acids directly (Mueller et al., 2006). These short-lived ROS produced in different cellular compartments, including plasma membrane, plastids, mitochondria, peroxisomes, endoplasmic reticulum, and cytosol, are thought to oxidize predominantly glycerolipids close to the site of ROS production. In a recent study, 1 O 2 was shown to be a major ROS species involved in photooxidative lipid oxidation and damage in Arabidopsis (Arabidopsis thaliana) leaves (Triantaphylidès et al., 2008). However, the major sites and molecular targets of lipid oxidation as well as the relative contributions of different ROS species and LOXs to LPO and fragmentation have not been clarified.LOXs and ROS have also been implicat...

Small RNAs use a diversity of well-characterized mechanisms to repress mRNAs, but how they activate gene expression at the mRNA level remains not well understood. The predominant activation mechanism of Hfq-associated small RNAs has been translational control whereby base pairing with the target prevents the formation of an intrinsic inhibitory structure in the mRNA and promotes translation initiation. Here, we report a translation-independent mechanism whereby the small RNA RydC selectively activates the longer of two isoforms of cfa mRNA (encoding cyclopropane fatty acid synthase) in Salmonella enterica. Target activation is achieved through seed pairing of the pseudoknot-exposed, conserved 5 0 end of RydC to an upstream region of the cfa mRNA. The seed pairing stabilizes the messenger, likely by interfering directly with RNase E-mediated decay in the 5 0 untranslated region. Intriguingly, this mechanism is generic such that the activation is equally achieved by seed pairing of unrelated small RNAs, suggesting that this mechanism may be utilized in the design of RNA-controlled synthetic circuits. Physiologically, RydC is the first small RNA known to regulate membrane stability.

Different peroxidases, including 2-cysteine (2-Cys) peroxiredoxins (PRXs) and thylakoid ascorbate peroxidase (tAPX), have been proposed to be involved in the water-water cycle (WWC) and hydrogen peroxide (H 2 O 2 )-mediated signaling in plastids. We generated an Arabidopsis (Arabidopsis thaliana) double-mutant line deficient in the two plastid 2-Cys PRXs (2-Cys PRX A and B, 2cpa 2cpb) and a triple mutant deficient in 2-Cys PRXs and tAPX (2cpa 2cpb tapx). In contrast to wild-type and tapx singleknockout plants, 2cpa 2cpb double-knockout plants showed an impairment of photosynthetic efficiency and became photobleached under high light (HL) growth conditions. In addition, double-mutant plants also generated elevated levels of superoxide anion radicals, H 2 O 2 , and carbonylated proteins but lacked anthocyanin accumulation under HL stress conditions. Under HL conditions, 2-Cys PRXs seem to be essential in maintaining the WWC, whereas tAPX is dispensable. By comparison, this HL-sensitive phenotype was more severe in 2cpa 2cpb tapx triple-mutant plants, indicating that tAPX partially compensates for the loss of functional 2-Cys PRXs by mutation or inactivation by overoxidation. In response to HL, H 2 O 2 -and photooxidative stress-responsive marker genes were found to be dramatically up-regulated in 2cpa 2cpb tapx but not 2cpa 2cpb mutant plants, suggesting that HL-induced plastid to nucleus retrograde photooxidative stress signaling takes place after loss or inactivation of the WWC enzymes 2-Cys PRX A, 2-Cys PRX B, and tAPX.

Background: Cardiovascular diseases (CVDs) are the greatest cause of death globally, and their reduction is a key public-health target. High blood pressure (BP) affects 1 in 3 people in the United Kingdom, and previous studies have shown that milk consumption is associated with lower BP.Objective: We investigated whether intact milk proteins lower 24-h ambulatory blood pressure (AMBP) and other risk markers of CVD.Design: The trial was a double-blinded, randomized, 3-way–crossover, controlled intervention study. Forty-two participants were randomly assigned to consume 2 × 28 g whey protein/d, 2 × 28 g Ca caseinate/d, or 2 × 27 g maltodextrin (control)/d for 8 wk separated by a 4-wk washout. The effects of these interventions were examined with the use of a linear mixed-model ANOVA.Results: Thirty-eight participants completed the study. Significant reductions in 24-h BP [for systolic blood pressure (SBP): −3.9 mm Hg; for diastolic blood pressure (DBP): −2.5 mm Hg; P = 0.050 for both)] were observed after whey-protein consumption compared with control intake. After whey-protein supplementation compared with control intake, peripheral and central systolic pressures [−5.7 mm Hg (P = 0.007) and −5.4 mm Hg (P = 0.012), respectively] and mean pressures [−3.7 mm Hg (P = 0.025) and −4.0 mm Hg (P = 0.019), respectively] were also lowered. Flow-mediated dilation (FMD) increased significantly after both whey-protein and calcium-caseinate intakes compared with control intake [1.31% (P < 0.001) and 0.83% (P = 0.003), respectively]. Although both whey protein and calcium caseinate significantly lowered total cholesterol [−0.26 mmol/L (P = 0.013) and −0.20 mmol/L (P = 0.042), respectively], only whey protein decreased triacylglycerol (−0.23 mmol/L; P = 0.025) compared with the effect of the control. Soluble intercellular adhesion molecule 1 and soluble vascular cell adhesion molecule 1 were reduced after whey protein consumption (P = 0.011) and after calcium-caseinate consumption (P = 0.039), respectively, compared with after control intake.Conclusions: The consumption of unhydrolyzed milk proteins (56 g/d) for 8 wk improved vascular reactivity, biomarkers of endothelial function, and lipid risk factors. Whey-protein supplementation also lowered 24-h ambulatory SBP and DBP. These results may have important implications for public health. This trial was registered at clinicaltrials.gov as NCT02090842.

ORCID IDs: 0000-0003-3058-7570 (A.F.); 0000-0002-7910-9118 (J.S.); 0000-0001-8122-5460 (M.J.M.); 0000-0002-6332-1712 (J.V.-C.); 0000-0002-5605-7984 (J.H.)Soil salinity increasingly causes crop losses worldwide. Although roots are the primary targets of salt stress, the signaling networks that facilitate metabolic reprogramming to induce stress tolerance are less understood than those in leaves. Here, a combination of transcriptomic and metabolic approaches was performed in salt-treated Arabidopsis thaliana roots, which revealed that the group S1 basic leucine zipper transcription factors bZIP1 and bZIP53 reprogram primary C-and N-metabolism. In particular, gluconeogenesis and amino acid catabolism are affected by these transcription factors. Importantly, bZIP1 expression reflects cellular stress and energy status in roots. In addition to the well-described abiotic stress response pathway initiated by the hormone abscisic acid (ABA) and executed by SnRK2 (Snf1-RELATED-PROTEIN-KINASE2) and AREB-like bZIP factors, we identify a structurally related ABA-independent signaling module consisting of SnRK1s and S1 bZIPs. Crosstalk between these signaling pathways recruits particular bZIP factor combinations to establish at least four distinct gene expression patterns. Understanding this signaling network provides a framework for securing future crop productivity.