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Varani, Luca,Ramos, Andres,Cole, Pual T.,Neuhaus, David,Varani, Gabriele Korean Magnetic Resonance Society 1998 Journal of the Korean Magnetic Resonance Society Vol.2 No.2
The diversity of RNA functions ranges from storage and propagation of genetic information to enzymatic activity during RNA processing and protein synthesis. This diversity of functions requires an equally diverse arrays of structures, and, very often, the formation of functional RNA-protein complexes. Recognition of specific RNA signals by RNA-binding proteins is central to all aspects of post-transcriptional regulation of gene expression. We will describe how NMR is being used to understand at the atomic level how these important biological processes occur.
A novel small-molecule binds to the influenza A virus RNA promoter and inhibits viral replication
Lee, Mi-Kyung,Bottini, Angel,Kim, Meehyein,Bardaro, Michael F.,Zhang, Ziming,Pellecchia, Maurizio,Choi, Byong-Seok,Varani, Gabriele The Royal Society of Chemistry 2014 Chemical communications Vol.50 No.3
<P>Through screening by NMR spectroscopy, we discovered a novel scaffold (DPQ: 6,7-dimethoxy-2-(1-piperazinyl)-4-quinazolinamine) that binds specifically to the influenza A virus RNA promoter. The solution structure of the RNA–DPQ complex reported here demonstrates that the internal loop is the binding site of DPQ. The scaffold exhibits antiviral activity against influenza viruses.</P> <P>Graphic Abstract</P><P>A novel scaffold (DPQ: 6,7-dimethoxy-2-(1-piperazinyl)-4-quinazolinamine) exhibiting anti-influenza cellular activity identified by NMR screening binds to the internal loop of the influenza A virus RNA promoter. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=c3cc46973e'> </P>
Amelioration of Cerebral Ischemic Injury by a Synthetic Seco-nucleoside LMT497
Ryu, Sangwoo,Kwon, Joonha,Park, Hyeon,Choi, In-Young,Hwang, Sunyoung,Gajulapati, Veeraswamy,Lee, Joo Young,Choi, Yongseok,Varani, Katia,Borea, Pier Andrea,Ju, Chung,Kim, Won-Ki The Korean Society for Brain and Neural Science 2015 Experimental Neurobiology Vol.24 No.1
<P>Recently, we reported that the A3 adenosine receptor (A<SUB>3</SUB>AR) agonist LJ529 (2-chloro-N<SUP>6</SUP>-(3-iodobnzyl)-5'-N-methylcarbamoyl-4'-thioadenosine) reduces cerebral ischemic injury via inhibition of recruitment of peripheral inflammatory cells into ischemic brain lesion. A3AR agonists, however, are known to possess anti-platelet activity, which may deter the combination therapy with tissue plasminogen activator for the therapy of cerebral ischemic stroke. Thus, the present study investigates the neuroprotective/anti-ischemic effect of a synthetic seco-nucleoside, LMT497 ((<I>S</I>)-2-((<I>R</I>)-1-(2-chloro-6-(3-iodobenzylamino)-9<I>H</I>-purin-9-yl)-2-hydroxyethoxy)-3-hydroxy-<I>N</I>-methylpropanamide) with little anti-platelet activity. LMT497 neither showed A<SUB>3</SUB>AR binding activity nor anti-platelet activity. In our present study LMT497 significantly attenuated the injury/death of cortical neurons exposed to oxygen-glucose deprivation (OGD) followed by re-oxygenation (R). LMT497 significantly reduced the ascending cellular level of reactive oxygen species under ischemic conditions by increasing the superoxide dismutase (SOD) levels. LMT497 also inhibited the migration of microglia which mediates inflammatory responses in ischemia. In rats subjected to middle cerebral artery occlusion (MCAO, 1.5 h) followed by reperfusion, LMT497 largely reduced brain infarction volume, and edema, and improved neurological score. Therapeutic efficacy of LMT497 was obtained by twice treatments even at 10 h and 18 h after the onset of ischemia. Collectively, LMT497 could be a therapeutic drug candidate with a wide therapeutic time window for the treatment of cerebral ischemic stroke.</P>
Aminoglycoside antibiotics bind to the influenza A virus RNA promoter
Kim, Henna,Lee, Mi-Kyung,Ko, Junsang,Park, Chin-Ju,Kim, Meehyein,Jeong, Yujeong,Hong, Sungwoo,Varani, Gabriele,Choi, Byong-Seok The Royal Society of Chemistry 2012 Molecular bioSystems Vol.8 No.11
<P>Aminoglycosides bind to the influenza A virus promoter (vRNA) at submicromolar concentration. The complex structure between the vRNA and neomycin illustrates that binding of neomycin causes a conformational change which would affect further transcription processes. Thus, aminoglycosides represent lead compounds for the discovery of antiviral therapeutics against influenza A virus.</P> <P>Graphic Abstract</P><P>Aminoglycosides bind to the influenza A virus promoter (vRNA) and cause a conformational change which is anticipated to prevent influenza A virus RdRp binding. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=c2mb25333j'> </P>
Wireless Communication at 310 GHz Using GaAs High-Electron-Mobility Transistors for Detection
Stéphane Blin,Lucie Tohme,Dominique Coquillat,Shogo Horiguchi,Yusuke Minamikata,Shintaro Hisatake,Philippe Nouvel,Thomas Cohen,Annick Pénarier,Fabrice Cano,Luca Varani,Wojciech Knap,Tadao Nagatsuma 한국통신학회 2013 Journal of communications and networks Vol.15 No.6
We report on the first error-free terahertz (THz) wirelesscommunication at 0.310 THz for data rates up to 8.2 Gbps using a18-GHz-bandwidth GaAs/AlGaAs field-effect transistor as a detector. This result demonstrates that low-cost commercially-availableplasma-wave transistors whose cut-off frequency is far below THzfrequencies can be employed in THz communication. Wirelesscommunication over 50 cm is presented at 1.4 Gbps using a unitravelling-carrier photodiode as a source. Transistor integration isdetailed, as it is essential to avoid any deleterious signals that wouldprevent successful communication. We observed an improvementof the bit error rate with increasing input THz power, followed bya degradation at high input power. Such a degradation appearsat lower powers if the photodiode bias is smaller. Higher-dataratecommunication is demonstrated using a frequency-multipliedsource thanks to higher output power. Bit-error-ratemeasurementsat data rates up to 10 Gbps are performed for different inputTHz powers. As expected, bit error rates degrade as data rate increases. However, degraded communication is observed at somespecific data rates. This effect is probably due to deleterious cavityeffects and/or impedance mismatches. Using such a system, realtimeuncompressed high-definition video signal is successfully androbustly transmitted.
Wireless Communication at 310 GHz using GaAs High-Electron-Mobility Transistors for Detection
Blin, Stephane,Tohme, Lucie,Coquillat, Dominique,Horiguchi, Shogo,Minamikata, Yusuke,Hisatake, Shintaro,Nouvel, Philippe,Cohen, Thomas,Penarier, Annick,Cano, Fabrice,Varani, Luca,Knap, Wojciech,Nagats The Korea Institute of Information and Commucation 2013 Journal of communications and networks Vol.15 No.6
We report on the first error-free terahertz (THz) wireless communication at 0.310 THz for data rates up to 8.2 Gbps using a 18-GHz-bandwidth GaAs/AlGaAs field-effect transistor as a detector. This result demonstrates that low-cost commercially-available plasma-wave transistors whose cut-off frequency is far below THz frequencies can be employed in THz communication. Wireless communication over 50 cm is presented at 1.4 Gbps using a uni-travelling-carrier photodiode as a source. Transistor integration is detailed, as it is essential to avoid any deleterious signals that would prevent successful communication. We observed an improvement of the bit error rate with increasing input THz power, followed by a degradation at high input power. Such a degradation appears at lower powers if the photodiode bias is smaller. Higher-data-rate communication is demonstrated using a frequency-multiplied source thanks to higher output power. Bit-error-rate measurements at data rates up to 10 Gbps are performed for different input THz powers. As expected, bit error rates degrade as data rate increases. However, degraded communication is observed at some specific data rates. This effect is probably due to deleterious cavity effects and/or impedance mismatches. Using such a system, realtime uncompressed high-definition video signal is successfully and robustly transmitted.