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Thomas, Ajesh P.,Palanikumar, L.,Jeena, M. T.,Kim, Kibeom,Ryu, Ja-Hyoung Royal Society of Chemistry 2017 Chemical Science Vol.8 No.12
<▼1><P>Herein, we introduce an indocyanine derivative (<B>IR-Pyr</B>) that is highly water soluble, exhibiting higher mitochondrial targetability and better photostability than IR-780.</P></▼1><▼2><P>Mitochondria-targeted cancer therapies have proven to be more effective than other similar non-targeting techniques, especially in photodynamic therapy (PDT). Indocyanine dye derivatives, particularly IR-780, are widely known for their PDT utility. However, poor water solubility, dark toxicity, and photobleaching are limiting factors for these dyes, which otherwise show promise based on their good absorption in the near-infrared (NIR) region and mitochondria targeting ability. Herein, we introduce an indocyanine derivative (<B>IR-Pyr</B>) that is highly water soluble, exhibiting higher mitochondrial targetability and better photostability than IR-780. Furthermore, electrostatic interactions between the positively charged <B>IR-Pyr</B> and negatively charged hyaluronic acid (HA) were utilized to construct a micellar aggregate that is selective towards cancer cells. The cancer mitochondria-targeted strategy confirms high PDT efficacy as proved by <I>in vitro</I> and <I>in vivo</I> experiments.</P></▼2>
Knockout of the Ribonuclease Inhibitor Gene Leaves Human Cells Vulnerable to Secretory Ribonucleases
Thomas, Sydney P.,Kim, Eunji,Kim, Jin-Soo,Raines, Ronald T. American Chemical Society 2016 Biochemistry Vol.55 No.46
<P>Ribonuclease inhibitor (RNH1) is a cytosolic protein that binds with femtomolar affinity to human ribonuclease 1 (RNase 1) and homologous secretory ribonucleases. RNH1 contains 32 cysteine residues and has been implicated as an antioxidant. Here, we use CRISPR-Cas9 to knock out RNH1 in HeLa cells. We find that cellular RNH1 affords marked protection from the lethal ribonucleolytic activity of RNase 1 but not from oxidants. We conclude that RNH1 protects cytosolic RNA from invading ribonucleases.</P>
Role of Intertube Interactions in Double- and Triple-Walled Carbon Nanotubes
Hirschmann, Thomas Ch.,Araujo, Paulo T.,Muramatsu, Hiroyuki,Rodriguez-Nieva, Joaquin F.,Seifert, Max,Nielsch, Kornelius,Kim, Yoong Ahm,Dresselhaus, Mildred S. American Chemical Society 2014 ACS NANO Vol.8 No.2
<P>Resonant Raman spectroscopy studies are performed to access information about the intertube interactions and wall-to-wall distances in double- and triple-walled carbon nanotubes. Here, we explain how the surroundings of the nanotubes in a multiwalled system influence their radial breathing modes. Of particular interest, the innermost tubes in double- and triple-walled carbon nanotube systems are shown to be significantly shielded from environmental interactions, except for those coming from the intertube interaction with their own respective host tubes. From a comparison of the Raman results for bundled as well as individual fullerene-peapod-derived double- and triple-walled carbon nanotubes, we observe that metallic innermost tubes, when compared to their semiconducting counterparts, clearly show weaker intertube interactions. Additionally, we discuss a correlation between the wall-to-wall distances and the frequency upshifts of the radial breathing modes observed for the innermost tubes in individual double- and triple-walled carbon nanotubes. All results allow us to contemplate fundamental properties related to DWNTs and TWNTs, as for example diameter- and chirality-dependent intertube interactions. We also discuss differences in fullerene-peapod-derived and chemical vapor deposition grown double- and triple-walled systems with the focus on mechanical coupling and interference effects.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/ancac3/2014/ancac3.2014.8.issue-2/nn500420s/production/images/medium/nn-2014-00420s_0008.eps'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/nn500420s'>ACS Electronic Supporting Info</A></P>
Jeon, B.T.,Kim, M.H.,Lee, S.M.,Thomas, David G.,Moon, S.H. Asian Australasian Association of Animal Productio 2006 Animal Bioscience Vol.19 No.9
The aim of this study was to provide basic haematological information to allow improved nutritional management for velvet production in spotted deer (Cervus nippon) by investigating biochemical changes in blood values during the antler growth period. Blood samples, obtained from the jugular vein of twenty-five deer, were taken every 10 days from casting (day 0) to harvesting (day 50) of velvet antler. Negligible changes were found in the concentrations of total protein, albumin, and creatinine during the antler growth period, but there were significant changes in the concentrations of urea (p<0.05) and uric acid (p<0.01). The concentration of triglyceride was significantly higher (p<0.05) during the antler growth period compared to casting time, while serum high-density lipoprotein concentrations were low and remained unchanged during the antler growth period. Serum glucose concentration increased (p<0.05) significantly and was slightly changeable during antler growth. The serum concentrations of Ca and P did not fluctuate during antler growth, while those of Na, K and Cl showed slight differences between the time of casting and the rest of the antler growth period. No significant changes in concentrations of AST, ALT, amylase, CK, GGT and LDH were detected during the antler growth period. However, the concentration of ALK-P increased during antler growth reaching its peak on day 50 after casting. We found a significant difference in the concentration of ALK-P between the time of casting and the rest of the antler growth period (p<0.01). Consequently, antler growth was associated with mild changes in measured serum biochemical values with the exception of ALK-P activity in spotted deer.
Palanikumar, L.,Kim, Ho Young,Oh, Joon Yong,Thomas, Ajesh P.,Choi, Eun Seong,Jeena, M. T.,Joo, Sang Hoon,Ryu, Ja-Hyoung American Chemical Society 2015 Biomacromolecules Vol.16 No.9
<P>Advances in water-insoluble drug delivery systems are limited by selective delivery, loading capacity, and colloidal and encapsulation stability. We have developed a simple and robust hydrophobic-drug delivery platform with different types of hydrophobic chemotherapeutic agents using a noncovalent gatekeeper’s technique with mesoporous silica nanoparticles (MSNs). The unmodified pores offer a large volume of drug loading capacity, and the loaded drug is stably encapsulated until it enters the cancer cells owing to the noncovalently bound polymer gatekeeper. In the presence of polymer gatekeepers, the drug-loaded mesoporous silica nanoparticles showed enhanced colloidal stability. The simplicity of drug encapsulation allows any combination of small chemotherapeutics to be coencapsulated and thus produce synergetic therapeutic effects. The disulfide moiety facilitates decoration of the nanoparticles with cysteine containing ligands through thiol–disulfide chemistry under mild conditions. To show the versatility of drug targeting to cancer cells, we decorated the surface of the shell-cross-linked nanoparticles with two types of peptide ligands, SP94 and RGD. The nanocarriers reported here can release encapsulated drugs inside the reducing microenvironment of cancer cells via degradation of the polymer shell, leading to cell death.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/bomaf6/2015/bomaf6.2015.16.issue-9/acs.biomac.5b00589/production/images/medium/bm-2015-00589d_0010.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/bm5b00589'>ACS Electronic Supporting Info</A></P>
Martirez, John Mark P.,Kim, Seungchul,Morales, Erie H.,Diroll, Benjamin T.,Cargnello, Matteo,Gordon, Thomas R.,Murray, Christopher B.,Bonnell, Dawn A.,Rappe, Andrew M. American Chemical Society 2015 JOURNAL OF THE AMERICAN CHEMICAL SOCIETY - Vol.137 No.8
<P>In addition to composition, the structure of a catalyst is another fundamental determinant of its catalytic reactivity. Recently, anomalous Ti oxide-rich surface phases of ternary oxides have been stabilized as nonstoichiometric epitaxial overlayers. These structures give rise to different modes of oxygen binding, which may lead to different oxidative chemistry. Through density functional theory investigations and electrochemical measurements, we predict and subsequently show that such a TiO<SUB>2</SUB> double-layer surface reconstruction enhances the oxygen evolving activity of the perovskite-type oxide SrTiO<SUB>3</SUB>. Our theoretical work suggests that the improved activity of the restructured TiO<SUB>2</SUB>(001) surface toward oxygen formation stems from (i) having two Ti sites with distinct oxidation activity and (ii) being able to form a strong O–O moiety (which reduces overbonding at Ti sites), which is a direct consequence of (iii) having a labile lattice O that is able to directly participate in the reaction. Here, we demonstrate the improvement of the catalytic performance of a well-known and well-studied oxide catalyst through more modern methods of materials processing, predicted through first-principles theoretical modeling.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jacsat/2015/jacsat.2015.137.issue-8/ja511332y/production/images/medium/ja-2014-11332y_0008.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/ja511332y'>ACS Electronic Supporting Info</A></P>
Gwon, Gwang Hyeon,Kim, Youngran,Liu, Yaqi,Watson, Adam T.,Jo, Aera,Etheridge, Thomas J.,Yuan, Fenghua,Zhang, Yanbin,Kim, YoungChang,Carr, Anthony M.,Cho, Yunje Cold Spring Harbor Laboratory Press 2014 Genes & development Vol.28 No.20
<P>Fanconi anemia (FA) is an autosomal recessive genetic disorder caused by defects in FA genes responsible for processing DNA interstrand cross-links (ICLs). FA-associated nuclease (FAN1) is recruited to lesions by a monoubiquitinated FANCI–FANCD2 (ID) complex and participates in ICL repair. Here, Gwon et al. determined the crystal structure of <I>Pseudomonas aeruginosa</I> FAN1 (<I>Pa</I>FAN1) lacking the UBZ (ubiquitin-binding zinc) domain in complex with 5′ flap DNA. The <I>Pa</I>FAN1 structure provides insights into how FAN1 integrates with the FA complex to participate in ICL repair.</P><P>Fanconi anemia (FA) is an autosomal recessive genetic disorder caused by defects in any of 15 FA genes responsible for processing DNA interstrand cross-links (ICLs). The ultimate outcome of the FA pathway is resolution of cross-links, which requires structure-selective nucleases. FA-associated nuclease 1 (FAN1) is believed to be recruited to lesions by a monoubiquitinated FANCI–FANCD2 (ID) complex and participates in ICL repair. Here, we determined the crystal structure of <I>Pseudomonas aeruginosa</I> FAN1 (<I>Pa</I>FAN1) lacking the UBZ (ubiquitin-binding zinc) domain in complex with 5′ flap DNA. All four domains of the right-hand-shaped <I>Pa</I>FAN1 are involved in DNA recognition, with each domain playing a specific role in bending DNA at the nick. The six-helix bundle that binds the junction connects to the catalytic viral replication and repair (VRR) nuclease (VRR nuc) domain, enabling FAN1 to incise the scissile phosphate a few bases distant from the junction. The six-helix bundle also inhibits the cleavage of intact Holliday junctions. <I>Pa</I>FAN1 shares several conserved features with other flap structure-selective nucleases despite structural differences. A clamping motion of the domains around the wedge helix, which acts as a pivot, facilitates nucleolytic cleavage. The <I>Pa</I>FAN1 structure provides insights into how archaeal Holliday junction resolvases evolved to incise 5′ flap substrates and how FAN1 integrates with the FA complex to participate in ICL repair.</P>
Go, Y.Y.,Kim, Y.S.,Cheon, S.,Nam, S.,Ku, K.B.,Kim, M.,Cho, N.H.,Park, H.,Alison Lee, P.Y.,Lin, Y.C.,Tsai, Y.L.,Thomas Wang, H.T.,Balasuriya, U.B.R. American Society for Investigative Pathology and t 2017 The Journal of Molecular Diagnostics Vol.19 No.6
<P>Middle East respiratory syndrome (MERS) is an emerging zoonotic viral respiratory disease that was first identified in Saudi Arabia in 2012. In 2015, the largest MERS outbreak outside of the Middle East region occurred in the Republic of Korea. The rapid nosocomial transmission of MERS-coronavirus (MERS-CoV) in Korean health care settings highlighted the importance and urgent need for a rapid and reliable on-site diagnostic assay to implement effective control and preventive measures. Here, the evaluation and validation of two newly developed reverse transcription insulated isothermal PCR (RT-iiPCR) methods targeting the ORF1a and upE genes of MERS-CoV are described. Compared with World Health Organization recommended singleplex real-time quantitative RT-PCR (RT-qPCR) assays, both RT-iiPCR assays had comparable analytical sensitivity for the detection of MERS-CoV RNA in tissue culture fluid and in sputum samples spiked with infectious virus. Furthermore, clinical evaluation was performed with sputum samples collected from subjects with acute and chronic respiratory illnesses, including patients infected with MERS-CoV. The overall agreement values between the two RT-iiPCR assays and the reference RT-qPCR assays were 98.06% (95% CI, 94.43%-100%; K = 0.96) and 99.03% (95% CI, 95.88%-100%; K = 0.99) for ORF1a and upE assays, respectively. The ORF1a and upE MERS-CoV RT-iiPCR assays coupled with a field deployable system provide a platform for a highly sensitive and specific on-site tool for diagnosis of MERS-CoV infections.</P>