Regioselective catalytic acetoxylation of limonene

Two efficient strategies for a direct catalytic and regioselective acetoxylation of terpenes are described. Acetoxylated limonene derivatives were synthesized via palladium-catalyzed C-H activation utilizing para-benzoquinone (BQ) as reoxdidation agent and acetic acid as solvent and reactant. Addition of dimethyl sulfoxide (DMSO) to the catalytic system led to highly selective functionalization of the exocyclic double bond of limonene. This catalytic acetoxylation of limonene was further optimized with regard to a more sustainable and environmentally-friendly procedure. On the other hand{,} the use of an aerobic tandem catalytic system using iron(ii) phthalocyanine (Fe(Pc)) as co-catalyst{,} which acts as electron transfer mediator (ETM){,} enabled a highly selective acetoxylation of the endocyclic double bond of limonene with high conversions. Moreover{,} diacetoxylated products were prepared by a reaction sequence applying the aforementioned catalytic systems

Activation of the tryptophan/serotonin pathway is associated with severity and predicts outcomes in pneumonia: results of a long-term cohort study

As part of the immune defense during infection, an increase in enzyme activity of indoleamine 2,3-dioxygenase (IDO) leads to a breakdown of tryptophan to kynurenine. In previous animal studies, therapeutic antagonism of IDO resulted in reduced sepsis mortality. We investigated the prognostic ability of tryptophan, serotonin, kynurenine and IDO (represented by the ratio of kynurenine/tryptophan) to predict adverse clinical outcomes in patients with community-acquired pneumonia (CAP).; We measured tryptophan, serotonin and kynurenine on admission plasma samples from CAP patients included in a previous multicenter trial by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). We studied their association with inflammation (C-reactive protein), infection (procalcitonin) and clinical outcome.; Mortality in the 268 included patients was 45% within 6 years of follow-up. IDO and kynurenine showed a strong positive correlation with markers of infection (procalcitonin) and inflammation (C-reactive protein) as well as sepsis and CAP severity scores. Tryptophan showed similar, but negative correlations. In a multivariate regression analysis adjusted for age and comorbidities, higher IDO activity and lower tryptophan levels were strongly associated with short-term adverse outcome defined as death and/or ICU admission within 30 days with adjusted odds ratios of 9.1 [95% confidence interval (CI) 1.4-59.5, p=0.021] and 0.11 (95% CI 0.02-0.70, p=0.021). Multivariate analysis did not reveal significant associations for kynurenine and serotonin.; In hospitalized CAP patients, higher IDO activity and lower tryptophan levels independently predicted disease severity and short-term adverse outcome. Whether therapeutic modulation of IDO has positive effects on outcome needs further investigation

Deterministic polarization chaos from a laser diode

Fifty years after the invention of the laser diode and fourty years after the report of the butterfly effect - i.e. the unpredictability of deterministic chaos, it is said that a laser diode behaves like a damped nonlinear oscillator. Hence no chaos can be generated unless with additional forcing or parameter modulation. Here we report the first counter-example of a free-running laser diode generating chaos. The underlying physics is a nonlinear coupling between two elliptically polarized modes in a vertical-cavity surface-emitting laser. We identify chaos in experimental time-series and show theoretically the bifurcations leading to single- and double-scroll attractors with characteristics similar to Lorenz chaos. The reported polarization chaos resembles at first sight a noise-driven mode hopping but shows opposite statistical properties. Our findings open up new research areas that combine the high speed performances of microcavity lasers with controllable and integrated sources of optical chaos.Comment: 13 pages, 5 figure

Dangerous Skyrmions in Little Higgs Models

Skyrmions are present in many models of electroweak symmetry breaking where the Higgs is a pseudo-Goldstone boson of some strongly interacting sector. They are stable, composite objects whose mass lies in the range 10-100 TeV and can be naturally abundant in the universe due to their small annihilation cross-section. They represent therefore good dark matter candidates. We show however in this work that the lightest skyrmion states are electrically charged in most of the popular little Higgs models, and hence should have been directly or indirectly observed in nature already. The charge of the skyrmion under the electroweak gauge group is computed in a model-independent way and is related to the presence of anomalies in the underlying theory via the Wess-Zumino-Witten term.Comment: 31 pages, 4 figures; v2: minor changes, one reference added, version to appear in JHEP; v3: erratum added, conclusions unchange

Evolution of the Solar Activity over Time and Effects on Planetary Atmospheres: I. High-energy Irradiances (1-1700 A)

We report on the results of the Sun in Time multi-wavelength program (X-rays to the UV) of solar analogs with ages covering ~0.1-7 Gyr. The chief science goals are to study the solar magnetic dynamo and to determine the radiative and magnetic properties of the Sun during its evolution across the main sequence. The present paper focuses on the latter goal, which has the ultimate purpose of providing the spectral irradiance evolution of solar-type stars to be used in the study and modeling of planetary atmospheres. The results from the Sun in Time program suggest that the coronal X-ray-EUV emissions of the young main-sequence Sun were ~100-1000 times stronger than those of the present Sun. Similarly, the transition region and chromospheric FUV-UV emissions of the young Sun are expected to be 20-60 and 10-20 times stronger, respectively, than at present. When considering the integrated high-energy emission from 1 to 1200 A, the resulting relationship indicates that the solar high-energy flux was about 2.5 times the present value 2.5 Gyr ago and about 6 times the present value about 3.5 Gyr ago (when life supposedly arose on Earth). The strong radiation emissions inferred should have had major influences on the thermal structure, photochemistry, and photoionization of planetary atmospheres and also played an important role in the development of primitive life in the Solar System. Some examples of the application of the Sun in Time results on exoplanets and on early Solar System planets are discussed.Comment: 20 pages, 8 figures, accepted for publication in Ap

Identifying Insects with Incomplete DNA Barcode Libraries, African Fruit Flies (Diptera: Tephritidae) as a Test Case

We propose a general working strategy to deal with incomplete reference libraries in the DNA barcoding identification of species. Considering that (1) queries with a large genetic distance with their best DNA barcode match are more likely to be misidentified and (2) imposing a distance threshold profitably reduces identification errors, we modelled relationships between identification performances and distance thresholds in four DNA barcode libraries of Diptera (n = 4270), Lepidoptera (n = 7577), Hymenoptera (n = 2067) and Tephritidae (n = 602 DNA barcodes). In all cases, more restrictive distance thresholds produced a gradual increase in the proportion of true negatives, a gradual decrease of false positives and more abrupt variations in the proportions of true positives and false negatives. More restrictive distance thresholds improved precision, yet negatively affected accuracy due to the higher proportions of queries discarded (viz. having a distance query-best match above the threshold). Using a simple linear regression we calculated an ad hoc distance threshold for the tephritid library producing an estimated relative identification error <0.05. According to the expectations, when we used this threshold for the identification of 188 independently collected tephritids, less than 5% of queries with a distance query-best match below the threshold were misidentified. Ad hoc thresholds can be calculated for each particular reference library of DNA barcodes and should be used as cut-off mark defining whether we can proceed identifying the query with a known estimated error probability (e.g. 5%) or whether we should discard the query and consider alternative/complementary identification methods

In utero exposure to benzo[a]pyrene increases mutation burden in the soma and sperm of adult mice

Background: Mosaicism, the presence of genetically distinct cell populations within an organism, has emerged as an important contributor to disease. Mutational events occurring during embryonic development can cause mosaicism in any tissue, but the influence of environmental factors on levels of mosaicism is unclear. Objectives: We investigated whether in utero exposure to the widespread environmental mutagen benzo[a]pyrene (BaP) has an impact on the burden and distribution of mutations in adult mice. Methods: We used the Muta™Mouse transgenic rodent model to quantify and characterize mutations in the offspring of pregnant mice exposed to BaP during postconception days 7 through 16, covering the major period of organogenesis in mice. Next-generation DNA sequencing was then used to determine the spectrum of mutations induced in adult mice that were exposed to BaP during fetal development. Results: Mutation frequency was significantly increased in the bone marrow, liver, brain, and sperm of first filial generation (F1) males. Developing embryos accumulated more mutations and exhibited higher proportions of mosaicism than exposed adults, particularly in the brain. Decreased sperm count and motility revealed additional negative impacts on the reproductive function of F1 males. Conclusion: In utero exposure to environmental mutagens contributes to somatic and germline mosaicism, permanently affecting both the genetic health of the F1 and the population gene pool. Citation: Meier MJ, O’Brien JM, Beal MA, Allan B, Yauk CL, Marchetti F. 2017. In utero exposure to benzo[a]pyrene increases mutation burden in the soma and sperm of adult mice

Stress-induced dynamic regulation of mitochondrial STAT3 and its association with cyclophilin D reduces mitochondrial ROS production

Signal Transducer and Activator of Transcription 3 (STAT3) has been tied to various physiological and pathological functions, mainly as a transcription factor that translocates to the nucleus upon tyrosine phosphorylation induced by cytokine stimulation. In addition, a small pool of STAT3 resides in the mitochondria where it serves as a sensor for various metabolic stressors including reactive oxygen species (ROS). Mitochondrially-localized STAT3 largely exerts its effects through direct or indirect regulation of the activity of the electron transport chain (ETC). It has been assumed that STAT3 amounts in the mitochondria are static. We showed that various stimuli, including oxidative stress and cytokines, triggered a signaling cascade that resulted in a rapid loss of mitochondrially-localized STAT3. Recovery of the mitochondrial pool of STAT3 over time depended upon phosphorylation of Ser727 in STAT3 and new protein synthesis. Under these conditions, mitochondrially-localized STAT3 also became competent to bind to cyclophilin D (CypD). Binding of STAT3 to CypD was mediated by the N-terminus of STAT3, which was also important for reducing mitochondrial ROS production after oxidative stress. These results outline a role for mitochondrially-localized STAT3 in sensing and responding to external stimuli

In Vitro Proliferation of Adult Human Beta-Cells

A decrease in functional beta-cell mass is a key feature of type 2 diabetes. Glucagon-like peptide 1 (GLP-1) analogues induce proliferation of rodent beta-cells. However, the proliferative capacity of human beta-cells and its modulation by GLP-1 analogues remain to be fully investigated. We therefore sought to quantify adult human beta-cell proliferation in vitro and whether this is affected by the GLP-1 analogue liraglutide