Title	J Biomol Screen. 2012 Jan 27. [Epub ahead of print].
Authors	High-Throughput Screening for AntiInfluenza A Virus Drugs and Study of the Mechanism of Procyanidin on Influenza A VirusInduced Autophagy.
Institution	Dai J, Wang G, Li W, Zhang L, Yang J, Zhao X, Chen X, Xu Y, Li K.
Abstract	In this research, we have established a high-throughput screening (HTS) platform based on the influenza A virus (IAV) vRNA promoter.
Text	Using this HTS platform, we selected 35 medicinal plants out of 83 examples of traditional Chinese medicine and found that 7 examples had not been reported. After examining many previous reports, we found that Vaccinium angustifolium Ait., Vitis vinifera L, and Cinnamomum cassia Presl had a common active compound, procyanidin, and then determined the anti-IAV effect of procyanidin and explored its mechanism of action. With a plaque inhibition assay and a time-of-addition experiment, we found that procyanidin could inhibit the IAV replication at several stages of the life cycle. In the Western blot and EGFP-LC3 localization assays, we found that procyanidin could inhibit the accumulation of LC3II and the dot-like aggregation of EGFP-LC3. In the RT-PCR and Western blot assays, we found procyanidin could inhibit the expression of Atg7, Atg5, and Atg12. Finally, by the bimolecular fluorescence complementation-fluorescence resonance energy transfer and co-immunoprecipitation assays, we found that procyanidin could inhibit the formation of the Atg5-Atg12/Atg16 heterotrimer and the dissociation of the beclin1/bcl2 heterodimer. In conclusion, we have established an HTS platform and identified procyanidin as a novel and promising anti-IAV agent.
Pubmed ID	22286278

Anal Chem. 2011 Feb 15,83(4):1307-14. Epub 2011 Jan 24.
Title	Fluorescence near gold nanoparticles for DNA sensing..
Authors	Cheng Y, Stakenborg T, Van Dorpe P, Lagae L, Wang M, Chen H, Borghs G.
Institution	Imec, Kapeldreef 75, Leuven, Belgium.
Journal	Anal Chem. 2011 Feb 15,83(4):1307-14. Epub 2011 Jan 24.
Abstract	We investigated fluorescence quenching and enhancement near gold nanoparticles (GNP) of various sizes using fluorescently labeled hairpin DNA probes of different lengths.
Text	A closed hairpin caused intimate contact between the fluorophore and the gold, resulting in an efficient energy transfer (quenching). Upon hybridization with complementary DNA, the DNA probes were stretched yielding a strong increase in fluorescence signal. By carefully quantifying the amount of bound fluorescent probes and the GNP concentrations, we were able to determine the quenching and enhancement efficiencies. We also studied the size and distance dependence theoretically, using both FDTD simulations and the Gersten-Nitzan model and obtained a good agreement between experiments and theory. On the basis of experimental and theoretical studies, we report over 96.8% quenching efficiency for all particle sizes tested and a maximal signal increase of 1.23 after DNA hybridization. The described results also demonstrate the potential of gold nanoparticles for label free DNA sensing
Pubmed ID	21261273

Antiviral Res. 2011 Jul,91(1):72-80. doi: 10.1016/j.antiviral.2011.04.014. Epub 2011 May 5
Title	Development of Vaccinia reporter viruses for rapid, high content analysis of viral function at all stages of gene expression .
Authors	Dower K, Rubins KH, Hensley LE, Connor JH.
Institution	Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA
Journal	Antiviral Res. 2011 Jul,91(1):72-80. doi: 10.1016/j.antiviral.2011.04.014. Epub 2011 May 5
Abstract	Vaccinia virus is the prototypical orthopoxvirus of Poxviridae, a family of viruses that includes the human pathogens Variola (smallpox) and Monkeypox.
Text	Core viral functions are conserved among orthopoxviruses, and consequently Vaccinia is routinely used to study poxvirus biology and screen for novel antiviral compounds. Here we describe the development of a series of fluorescent protein-based reporter Vaccinia viruses that provide unprecedented resolution for tracking viral function. The reporter viruses are divided into two sets: (1) single reporter viruses that utilize temporally regulated early, intermediate, or late viral promoters, and (2) multi-reporter viruses that utilize multiple temporally regulated promoters. Promoter and reporter combinations were chosen that yielded high signal-to-background for stage-specific viral outputs. We provide examples for how these viruses can be used in the rapid and accurate monitoring of Vaccinia function and drug action.
Pubmed ID	21569797

Bioorg Med Chem Lett. 2011 Jun 30
Title	Identification of a non-phosphorylated, cell permeable, small molecule ligand for the Stat3 SH2 domain .
Authors	Page BD, Fletcher S, Yue P, Li Z, Zhang X, Sharmeen S, Datti A, Wrana JL, Trudel S, Schimmer AD, Turkson J, Gunning PT.
Institution	Department of Chemistry, University of Toronto Mississauga, 3359 Mississauga Road, Mississauga, ON, Canada L5L 1C6.
Journal	Bioorg Med Chem Lett. 2011 Jun 30
Abstract	Signal transducer and activator of transcription 3 (Stat3) protein is a cytosolic transcription factor that is aberrantly activated in numerous human cancers. Inhibitors of activated Stat3-Stat3 protein complexes have been shown to hold therapeutic promise for the treatment of human cancers harboring activated Stat3.
Text	Herein, we report the design and synthesis of a focused library of salicylic acid containing Stat3 SH2 domain binders. The most potent inhibitor, 17o, effectively disrupted Stat3-phosphopeptide complexes (K(i)=13µM), inhibited Stat3-Stat3 protein interactions (IC(50)=19µM) and silenced intracellular Stat3 phosphorylation and Stat3-target gene expression profiles. Inhibition of Stat3 function in both breast and multiple myeloma (MM) tumor cells correlated with induced cell death (EC(50)=10 and 16µM, respectively).
Pubmed ID	21788134

Biosci Rep. 2011 Mar 2,31(4):283-94.
Title	Molecular determinants involved in activation of caspase 7.
Authors	Boucher D, Blais V, Drag M, Denault JB.
Institution	Department of Pharmacology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, Canada J1H 5N4
Journal	Biosci Rep. 2011 Mar 2,31(4):283-94.
Abstract	During apoptosis, initiator caspases (8, 9 and 10) activate downstream executioner caspases (3, 6 and 7) by cleaving the IDC (interdomain connector) at two sites. Here, we demonstrate that both activation sites, site 1 and site 2, of caspase 7 are suboptimal for activation by initiator caspases 8 and 9 in cellulo, and in vitro using recombinant proteins and activation kinetics.
Text	Indeed, when both sites are replaced with the preferred motifs recognized by either caspase 8 or 9, we found an up to 36-fold improvement in activation. Moreover, cleavage at site 1 is preferred to site 2 because of its location within the IDC, since swapping sites does not lead to a more efficient activation. We also demonstrate the important role of Ile195 of site 1 involved in maintaining a network of contacts that preserves the proper conformation of the active enzyme. Finally, we show that the length of the IDC plays a crucial role in maintaining the necessity of proteolysis for activation. In fact, although we were unable to generate a caspase 7 that does not require proteolysis for activity, shortening the IDC of the initiator caspase 8 by four residues was sufficient to confer a requirement for proteolysis, a key feature of executioner caspases. Altogether, the results demonstrate the critical role of the primary structure of caspase 7's IDC for its activation and proteolytic activity.
Pubmed ID	20942802

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