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Song, Min-Hee,Lee, Jang-Won,Kim, Min Su,Yoon, Ja-Kyung,White, Theodore C.,Floyd, Anna,Heitman, Joseph,Strain, Anna K.,Nielsen, Judith N.,Nielsen, Kirsten,Bahn, Yong-Sun American Society for Microbiology 2012 EUKARYOTIC CELL Vol.11 No.1
<B>ABSTRACT</B><P> Cryptococcosis, caused by the basidiomycetous fungus Cryptococcus neoformans , is responsible for more than 600,000 deaths annually in AIDS patients. Flucytosine is one of the most commonly used antifungal drugs for its treatment, but its resistance and regulatory mechanisms have never been investigated at the genome scale in C. neoformans . In the present study, we performed comparative transcriptome analysis by employing two-component system mutants ( <I>tco1</I> Δ and <I>tco2</I> Δ) exhibiting opposing flucytosine susceptibility. As a result, a total of 177 flucytosine-responsive genes were identified, and many of them were found to be regulated by Tco1 or Tco2. Among these, we discovered an APSES-like transcription factor, Mbs1 ( Mb p1- and S wi4-like protein 1). Expression analysis revealed that <I>MBS1</I> was regulated in response to flucytosine in a Tco2/Hog1-dependent manner. Supporting this, C. neoformans with the deletion of <I>MBS1</I> exhibited increased susceptibility to flucytosine. Intriguingly, Mbs1 played pleiotropic roles in diverse cellular processes of C. neoformans . Mbs1 positively regulated ergosterol biosynthesis and thereby affected polyene and azole drug susceptibility. Mbs1 was also involved in genotoxic and oxidative stress responses. Furthermore, Mbs1 promoted production of melanin and capsule and thereby was required for full virulence of C. neoformans . In conclusion, Mbs1 is considered to be a novel antifungal therapeutic target for treatment of cryptococcosis. </P>
Hardstone, Melissa C,Strycharz, Joseph P,Kim, Junheon,Park, Il‐,Kwon,Yoon, Kyong Sup,Ahn, Young Joon,Harrington, Laura C,Lee, Si Hyeock,Clark, J Marshall John Wiley Sons, Ltd 2015 Pest Management Science Vol.71 No.6
<P><B>Abstract</B></P><P><B>BACKGROUND</B></P><P>Pyrethroids are the insecticides of choice when exposure to humans is likely, such as occurs in vector and public‐health‐related control programs. Unfortunately, the pyrethroids share a common resistance mechanism with dichlorodiphenyltrichloroethane (DDT), knockdown resistance (<I>kdr</I>), and prior extensive use of DDT has predisposed the pyrethroids to cross‐resistance via <I>kdr</I>. Given the widespread occurrence of <I>kdr</I>, the use of synergists with pyrethroids is considered to be prudent to guard against the selection of multiply resistant insects.</P><P><B>RESULTS</B></P><P>3‐Phenoxybenzyl hexanoate (PBH) was synthesized as a multifunctional pyrethroid synergist that, besides being a surrogate substrate for sequestration/hydrolytic carboxylesterases, now also functions as a substrate for oxidative xenobiotic metabolism. The addition of PBH to permethrin‐treated females of the ISOP450 strain of <I>Culex pipiens quinquefasciatus</I> resulted in a threefold increase in synergism, as judged by the synergistic ratio. Similarly, PBH synergized the action of deltamethrin sixfold on females of the common bed bug, <I>Cimex lectularius</I>, and was 2.8‐fold more synergistic than piperonyl butoxide (PBO).</P><P><B>CONCLUSIONS</B></P><P>PBH synergized the action of both type I and type II pyrethroids in a mosquito vector (<I>Cx. p. quinquefasciatus</I>) and in a public‐health pest, <I>C. lectularius</I>, respectively, indicating a broad spectrum of action on blood‐feeding insects. PBH appears to have residual properties similar to permethrin and is itself non‐toxic, unlike PBO, and therefore should be compatible with existing pyrethroid formulations used for insecticide‐treated nets and home/residential sprays. © 2014 Society of Chemical Industry</P>
Reish, Matthew E.,Huff, Gregory S.,Lee, Wonho,Uddin, Mohammad Afsar,Barker, Alex J.,Gallaher, Joseph K.,Hodgkiss, Justin M.,Woo, Han Young,Gordon, Keith C. American Chemical Society 2015 Chemistry of materials Vol.27 No.8
<P>The electronic properties of the donor–acceptor (DA) polymer poly{5,6-bis(octyloxy)-4-(thiophen-2-yl)benzo[<I>c</I>]-1,2,5-thiadiazole} (PTBT) have been investigated using spectroscopic and computational techniques. Electronic absorption and emission spectra reveal the presence of an ordered and a disordered phase in solution. Franck–Condon modeling of the ordered phase yields Huang–Rhys factors of 0.55 (20 °C) and 0.51 (−180 °C), indicating little structural distortion between ground and excited state. DFT calculations with resonance Raman spectroscopy are consistent with a lowest energy excited state that is electronically delocalized and has little charge-transfer character, unexpected for a copolymer with a low bandgap (∼1.8 eV). Transient absorption spectroscopy of PTBT:fullerene blends reveals near-unity internal charge-transfer yields in both ordered and disordered film morphologies. In the disordered blend, charge transfer is complete within the laser pulse (100 fs), whereas the ordered blend also features a slower phase due to exciton diffusion in the phase separated morphology. In the ordered blend, the spectra and dynamics of charge transfer reveal that excitons and charges promptly occupy delocalized states on extended polymer chains. The pervasive use of donor–acceptor structures in polymer devices makes understanding the interplay of morphology and electronic structure of these polymers essential and here a spectroscopic and computational investigation gives an extensive picture of the electronic properties and their effect on charge dynamics in a DA polymer.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/cmatex/2015/cmatex.2015.27.issue-8/cm504655f/production/images/medium/cm-2014-04655f_0009.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/cm504655f'>ACS Electronic Supporting Info</A></P>
CO in Protostars (COPS): <i>Herschel</i>-SPIRE Spectroscopy of Embedded Protostars
Yang, Yao-Lun,Green, Joel D.,Evans II, Neal J.,Lee, Jeong-Eun,Jørgensen, Jes K.,Kristensen, Lars E.,Mottram, Joseph C.,Herczeg, Gregory,Karska, Agata,Dionatos, Odysseas,Bergin, Edwin A.,Bouwman, Jeroe American Astronomical Society 2018 The Astrophysical journal Vol.860 No.2
<P>We present full spectral scans from 200 to 670. mu m of 26 Class 0+I protostellar sources obtained with Herschel-SPIRE as part of the 'COPS-SPIRE' Open Time program, complementary to the DIGIT and WISH Key Programs. Based on our nearly continuous, line-free spectra from 200 to 670. mu m, the calculated bolometric luminosities (L-bol) increase by 50%. on average, and the bolometric temperatures (T-bol) decrease by 10%. on average, in comparison with the measurements without Herschel. Fifteen protostars have the same class using Tbol and L-bol/L-smm. We identify rotational transitions of CO lines from J = 4 -> 3to J = 13 -> 12, along with emission lines of (CO)-C-13, HCO+, H2O, and [C I]. The ratios of (CO)-C-12 to (CO)-C-13 indicate that (CO)-C-12 emission remains optically thick for J(up) < 13. We fit up to four components of temperature from the rotational diagram with flexible break points to separate the components. The distribution of rotational temperatures shows a primary population around 100 K with a secondary population at similar to 350 K. We quantify the correlations of each line pair found in our data set and find that the strength of the correlation of CO lines decreases as the difference between J levels between two CO lines increases. The multiple origins of CO emission previously revealed by velocity-resolved profiles are consistent with this smooth distribution if each physical component contributes to a wide range of CO lines with significant overlap in the CO ladder. We investigate the spatial extent of CO emission and find that the morphology is more centrally peaked and less bipolar at high-J lines. We find the CO emission observed with SPIRE related to outflows, which consists of two components, the entrained gas and shocked gas, as revealed by our rotational diagram analysis, as well as the studies with velocity-resolved CO emission.</P>