Isolation and Characterization of Marine Pigmented Bacteria from Norwegian Coastal Waters and Screening for Carotenoids with UVA-Blue Light Absorbing Properties

Marit H. Stafsnes,Kjell D Josefsen,Trond E. Ellingsen,Geir Kildahl-Andersen,Svein Valla,Per Bruheim 한국미생물학회 2010 The journal of microbiology Vol.48 No.1

Microbial culture collections are important resources for isolation of natural compounds with novel properties. In this study, a culture collection of around 1,500 pigmented heterotrophic bacteria was established. The bacteria were isolated from the sea surface microlayer at different sampling sites along the mid-part of the Norwegian coast. The bacterial isolates produced pigments of various coloration (e.g. golden,yellow, red, pink and orange). Methanol extracts of sixteen isolates were characterized with LC-Diodearray-TOF mass spectrometry analysis. The number of pigments per isolate varied considerably, and a tentative identification of the pigments was performed based on UV-absorbance profile and molecular formula assignation based on the accurate mass determination. The LC-MS analyses revealed that most of the pigments probably were carotenoids. Furthermore, we developed a high throughput LC-MS method for characterization and screening of a larger sub-fraction (300 isolates) of the culture collection. The aim was to screen and identify bacterial isolates producing carotenoids that absorb light in the UVA-Blue light. Six of the bacterial strains were selected for detailed investigation, including 16s rRNA sequencing, preparative HPLC for purification of major carotenoids and subsequent structural elucidation with NMR. Among the identified carotenoids were zeaxanthin, nostoxanthin and sarcinaxanthin, some with novel glycosylation patterns.

Raman Spectroscopy of Fluoropolymer Conformal Coatings on Electronic Boards

Mirjana Rodošek,Lidija Slemenik Perše,Mohor Mihelčič,Matjaž Koželj,Boris Orel,Başak Bengű,Onder Sunetci,Pauli Pori,Angela Šurca Vuk 대한금속·재료학회 2014 ELECTRONIC MATERIALS LETTERS Vol.10 No.5

Fluoropolymer conformal coatings were applied to electronic boards (EBs) and cured at room temperature or 80°C. The coatings were first deposited on model substrate, i.e. aluminium alloy AA 2024 and tested for their anticorrosion properties with a potentiodynamic polarisation technique. The cathodic current densities ranged from 10−9 - 10−10 A/cm2, approaching the lower current limit after the addition of TiO2 nanoparticles into the formulation. Application of fluoropolymer-based formulation was performed via spray-coating deposition. Examination of the coverage of EBs under UV light, which is commonly used in industry, revealed that some components might not be entirely covered. In the search for other possible analytical tools of coverage with protective coatings, optical microscopy and confocal Raman spectroscopy were investigated.

Buparlisib plus fulvestrant in postmenopausal women with hormone-receptor-positive, HER2-negative, advanced breast cancer progressing on or after mTOR inhibition (BELLE-3): a randomised, double-blind, placebo-controlled, phase 3 trial

Di Leo, Angelo,Johnston, Stephen,Lee, Keun Seok,Ciruelos, Eva,Lønning, Per E,Janni, Wolfgang,O'Regan, Ruth,Mouret-Reynier, Marie-Ange,Kalev, Dimitar,Egle, Daniel,Cső,szi, Tibor,Bordonaro, Roberto Elsevier 2018 The Lancet. Oncology Vol.19 No.1

<P><B>Summary</B></P> <P><B>Background</B></P> <P>Activation of the PI3K/AKT/mTOR pathway occurs frequently in breast cancer that is resistant to endocrine therapy. Approved mTOR inhibitors effectively inhibit cell growth and proliferation but elicit AKT phosphorylation via a feedback activation pathway, potentially leading to resistance to mTOR inhibitors. We evaluated the efficacy and safety of buparlisib plus fulvestrant in patients with advanced breast cancer who were pretreated with endocrine therapy and mTOR inhibitors.</P> <P><B>Methods</B></P> <P>BELLE-3 was a randomised, double-blind, placebo-controlled, multicentre, phase 3 study. Postmenopausal women aged 18 years or older with histologically or cytologically confirmed hormone-receptor-positive, HER2-negative, locally advanced or metastatic breast cancer, who had relapsed on or after endocrine therapy and mTOR inhibitors, were recruited from 200 trial centres in 22 countries. Eligible patients were randomly assigned (2:1) via interactive response technology (block size of six) to receive oral buparlisib (100 mg per day) or matching placebo starting on day 1 of cycle 1, plus intramuscular fulvestrant (500 mg) on days 1 and 15 of cycle 1 and on day 1 of subsequent 28-day cycles. Randomisation was stratified by visceral disease status. The primary endpoint was progression-free survival by local investigator assessment as per the Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 in the full analysis population (all randomised patients, by intention-to-treat). Safety was analysed in all patients who received at least one dose of treatment and at least one post-baseline safety assessment. This study is registered with ClinicalTrials.gov, number NCT01633060, and is ongoing but no longer enrolling patients.</P> <P><B>Findings</B></P> <P>Between Jan 15, 2013, and March 31, 2016, 432 patients were randomly assigned to the buparlisib (n=289) or placebo (n=143) groups. Median progression-free survival was significantly longer in the buparlisib versus placebo group (3·9 months [95% CI 2·8–4·2] <I>vs</I> 1·8 months [1·5–2·8]; hazard ratio [HR] 0·67, 95% CI 0·53–0·84, one-sided p=0·00030). The most frequent grade 3–4 adverse events in the buparlisib versus placebo group were elevated alanine aminotransferase (63 [22%] of 288 patients <I>vs</I> four [3%] of 140), elevated aspartate aminotransferase (51 [18%] <I>vs</I> four [3%]), hyperglycaemia (35 [12%] <I>vs</I> none), hypertension (16 [6%] <I>vs</I> six [4%]), and fatigue (ten [3%] <I>vs</I> two [1%]). Serious adverse events were reported in 64 (22%) of 288 patients in the buparlisib group versus 23 (16%) of 140 in the placebo group; the most frequent serious adverse events (affecting ≥2% of patients) were elevated aspartate aminotransferase (six [2%] <I>vs</I> none), dyspnoea (six [2%] <I>vs</I> one [1%]), and pleural effusion (six [2%] <I>vs</I> none). On-treatment deaths occurred in ten (3%) of 288 patients in the buparlisib group and in six (4%) of 140 in the placebo group; most deaths were due to metastatic breast cancer, and two were considered treatment-related (cardiac failure [n=1] in the buparlisib group and unknown reason [n=1] in the placebo group).</P> <P><B>Interpretation</B></P> <P>The safety profile of buparlisib plus fulvestrant does not support its further development in this setting. Nonetheless, the efficacy of buparlisib supports the rationale for the use of PI3K inhibitors plus endocrine therapy in patients with <I>PIK3CA</I> mutations.</P> <P><B>Funding</B></P> <P>Novartis Pharmaceuticals Corporation.</P>

Sex-Chromosome Homomorphy in Palearctic Tree Frogs Results from Both Turnovers and X-Y Recombination.

Dufresnes, Christophe,Borz?e, Ama?l,Horn, Agn?s,St?ck, Matthias,Ostini, Massimo,Sermier, Roberto,Wassef, J?r?me,Litvinchuck, Spartak N,Kosch, Tiffany A,Waldman, Bruce,Jang, Yikweon,Brelsford, Alan,Per University of Chicago Press 2015 Molecular biology and evolution Vol.32 No.9

<P>Contrasting with birds and mammals, poikilothermic vertebrates often have homomorphic sex chromosomes, possibly resulting from high rates of sex-chromosome turnovers and/ or occasional X-Y recombination. Strong support for the latter mechanism was provided by four species of European tree frogs, which inherited from a common ancestor (similar to 5Ma) the same pair of homomorphic sex chromosomes (linkage group 1, LG1), harboring the candidate sex-determining gene Dmrt1. Here, we test sex linkage of LG1 across six additional species of the Eurasian Hyla radiation with divergence times ranging from 6 to 40 Ma. LG1 turns out to be sex linked in six of nine resolved cases. Mapping the patterns of sex linkage to the Hyla phylogeny reveals several transitions in sex-determination systems within the last 10My, including one switch in heterogamety. Phylogenetic trees of DNA sequences along LG1 are consistent with occasional X-Y recombination in all species where LG1 is sex linked. These patterns argue against one of the main potential causes for turnovers, namely the accumulation of deleteriousmutations on nonrecombining chromosomes. Sibship analyses show that LG1 recombination is strongly reduced in males from most species investigated, including some in which it is autosomal. Intrinsically low male recombination might facilitate the evolution of male heterogamety, and the presence of important genes from the sex-determination cascade might predispose LG1 to become a sex chromosome.</P>

Young capillary vessels rejuvenate aged pancreatic islets

Almaca, Joana,Molina, Judith,Arrojo e Drigo, Rafael,Abdulreda, Midhat H.,Jeon, Won Bae,Berggren, Per-Olof,Caicedo, Alejandro,Nam, Hong Gil National Academy of Sciences 2014 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.111 No.49

<P><B>Significance</B></P><P>The regulation of blood glucose is a homeostatic process that declines with age, but it is unknown whether this disturbance is a consequence of intrinsic dysfunction of the regulatory organ, the pancreatic islet. In marked contrast to the widely held notion that the insulin-producing pancreatic beta cell loses function with wear and tear, and thus causes age-related disturbances in glucose homeostasis, we show that mouse and human beta cells are fully functional at advanced age. The pancreatic islet as an organ, however, is threatened by vascular senescence. Replacing the islet vasculature in aged islet grafts rejuvenates the islet and fully restores glucose homeostasis, indicating that islet blood vessels should be targeted to mitigate frail glucose homeostasis associated with aging.</P><P>Pancreatic islets secrete hormones that play a key role in regulating blood glucose levels (glycemia). Age-dependent impairment of islet function and concomitant dysregulation of glycemia are major health threats in aged populations. However, the major causes of the age-dependent decline of islet function are still disputed. Here we demonstrate that aging of pancreatic islets in mice and humans is notably associated with inflammation and fibrosis of islet blood vessels but does not affect glucose sensing and the insulin secretory capacity of islet beta cells. Accordingly, when transplanted into the anterior chamber of the eye of young mice with diabetes, islets from old mice are revascularized with healthy blood vessels, show strong islet cell proliferation, and fully restore control of glycemia. Our results indicate that beta cell function does not decline with age and suggest that islet function is threatened by an age-dependent impairment of islet vascular function. Strategies to mitigate age-dependent dysregulation in glycemia should therefore target systemic and/or local inflammation and fibrosis of the aged islet vasculature.</P>

Validation of OMI tropospheric NO₂ observations during INTEX-B and application to constrain NO_x emissions over the eastern United States and Mexico

Boersma, K.F.,Jacob, D.J.,Bucsela, E.J.,Perring, A.E.,Dirksen, R.,van der A, R.J.,Yantosca, R.M.,Park, R.J.,Wenig, M.O.,Bertram, T.H.,Cohen, R.C. Pergamon Press ; Elsevier [distribution] 2008 Atmospheric environment Vol.42 No.19

We compare tropospheric NO<SUB>2</SUB> column measurements from the Ozone Monitoring Instrument (OMI) aboard the EOS Aura satellite with coincident in situ aircraft measurements on vertical spirals over the southern United States, Mexico, and the Gulf of Mexico during the INTEX-B campaign in March 2006. Good correlation with no significant bias (r<SUP>2</SUP>=0.67, slope=0.99+/-0.17, n=12) is found for the ensemble of comparisons when the aircraft could spiral sufficiently low to sample most of the NO<SUB>2</SUB> column. Urban spirals where large extrapolations were needed below the aircraft floor (1000ft) showed poorer agreement. We use the OMI observations together with a global chemical transport model (GEOS-Chem) to estimate emissions of nitrogen oxides over the eastern United States and Mexico in March 2006. Comparison to EPA's National Emissions Inventory 1999 (NEI99) calls for a decrease in power plant emissions and an increase in on-road vehicle emissions relative to that inventory. The rise in vehicular emissions is offsetting the reduction in power plant and industry emissions. These findings are consistent with independent assessments. Our OMI-derived emission estimates for Mexico are higher by a factor of 2.0+/-0.5 than bottom-up emissions, similar to a comparison between the recently released Mexican NEI99 inventory and the bottom-up showing that the Mexican NEI99 inventory is 1.6-1.8x higher.

Identification and Saturable Nature of Signaling Pathways Induced by Metreleptin in Humans: Comparative Evaluation of In Vivo, Ex Vivo, and In Vitro Administration

( Hyun-seuk Moon ),( Joo Young Huh ),( Fadime Dincer ),( Benjamin E. Schneider ),( Per-olof Hasselgren ),( Christos S. Mantzoros ) 전남대학교 약품개발연구소 2015 약품개발연구지 Vol.24 No.-

Signaling pathways activated by leptin in metabolically important organs have largely been studied only in animal and/or cell culture studies. In this study, we examined whether leptin has similar effects in human peripheral tissues in vivo, ex vivo, and in vitro and whether the response would be different in lean and obese humans. For in vivo leptin signaling, metreleptin was administered and muscle, adipose tissue, and peripheral blood mononuclear cells were taken for analysis of signal activation. Experiments were also done ex vivo and with primary cultured cells in vitro. The signal activation was compared between male versus female and obese versus lean humans. Acute in vivo, ex vivo, and/or in vitro metreleptin administration similarly activated STAT3, AMPK, ERK1/2, Akt, mTOR, NF-κB, and/or IKKα/β without any differences between male versus female and obese versus lean subjects. All signaling pathways were saturable at ~30-50 ng/mL, consistent with the clinical evidence showing no additional effect(s) in obese subjects who already have high levels of leptin. Our data provide novel information on downstream effectors of metreleptin action in humans that may have therapeutic implications.