Polyphenolic C-glucosidic ellagitannins present in oak-aged wine inhibit HIV-1 nucleocapsid protein

HIV-1 nucleocapsid protein (NC) is a nucleic acid chaperone implicated in several steps of the virus replication cycle and an attractive new target for drug development. In reverse transcription, NC destabilizes nucleic acid secondary structures and catalyzes the annealing of HIV-1 TAR RNA to its DNA copy (cTAR) to form the heteroduplex TAR/cTAR. A screening program led to the identification of the plant polyphenols acutissimins A and B as potent inhibitors of NC in different assays. These two flavano-ellagitannins, which are found in wine aged in oak barrels, exhibited different mechanisms of protein inhibition and higher potency relatively to their epimers, epiacutissimins A and B, and to simpler structures notably representing hydrolytic fragments and metabolites therefrom

Toward Whole-Brain Minimally-Invasive Vascular Imaging

Imaging the brain vasculature can be critical for cerebral perfusion monitoring in the context of neurocritical care. Although ultrasensitive Doppler (UD) can provide good sensitivity to cerebral blood volume (CBV) in a large field of view, it remains difficult to perform through the skull. In this work, we investigate how a minimally invasive burr hole, performed for intracranial pressure (ICP) monitoring, could be used to map the entire brain vascular tree. We explored the use of a small motorized phased array probe with a non-implantable preclinical prototype in pigs. The scan duration (18 min) and coverage (62 $\pm$ 12 % of the brain) obtained allowed global CBV variations detection (relative in brain Dopplerdecrease =-3[-4-+16]% \& Dopplerincrease. = +1[-3-+15]%, n = 6 \& 5) and stroke detection (relative in core Dopplerstroke. =-25%, n = 1). This technology could one day be miniaturized to be implanted for brain perfusion monitoring in neurocritical care

Développement de sondes moléculaires appliquées à l'étude de la biosynthèse des flavonoïdes

Les flavonoïdes sont des substances naturelles connues pour leurs propriétés anti-inflammatoires, anti-cancéreuses ou anti-virales chez l'homme. Chez les végétaux, ils participent notamment à leur protection vis-à-vis d'organismes pathogènes. La voie de biosynthèse des flavonoïdes est l'une des plus étudiées chez les plantes et notamment chez la vigne : Vitis vinifera. Cependant, la ou les enzymes impliquées dans les dernières étapes de biosynthèse conduisant aux anthocyanes et aux proanthocyanidines restent, à ce jour, peu ou pas connues. L étude que nous proposons a pour but de concevoir des sondes moléculaires d affinité susceptibles d interagir avec une ou plusieurs enzymes impliquées dans ces dernières étapes de biosynthèse. Ces sondes, basées sur la technologie émergeante de protéomique chimique : Activity- and affininity Based Protein Profiling (ABPP), ont été validées à l aide d une enzyme modèle : la leucoanthocyanidine dioxygénase (LDOX). Elles ont ensuite été appliquées à des extraits complexes de protéines issus de Vitis vinifera.Flavonoids are natural substances known for their anti-inflammatory, anti-cancerous and anti-virals properties in humans. In plants, they are one of the molecules responsible for fighting pathogens. The flavonoid biosynthesis pathway as been greatly studied in plants, especially in that of the grapevine: Vitis vinifera. However, detailed studies of the exact function of the enzymes involved in the last steps of the biosynthesis of anthocyanins and proanthocyanidins remains largely lacking.The study that we propose is to synthesize molecular probes designed to specifically interact with enzymes involved in the last stages of flavonoids biosynthesis. Our probes, based on the emerging chemical proteomic technology, activity- and affinity based protein profiling (ABPP), were validated with a model enzyme: leucoanthocyanidin dioxygenase (LDOX). After which, they were used with complex protein mixtures from Vitis vinifera.BORDEAUX1-Bib.electronique (335229901) / SudocSudocFranceF

Rapid Screening of Ellagitannins in Natural Sources via Targeted Reporter Ion Triggered Tandem Mass Spectrometry

Complex biomolecules present in their natural sources have been difficult to analyze using traditional analytical approaches. Ultrahigh-performance liquid chromatography (UHPLC-MS/MS) methods have the potential to enhance the discovery of a less well characterized and challenging class of biomolecules in plants, the ellagitannins. We present an approach that allows for the screening of ellagitannins by employing higher energy collision dissociation (HCD) to generate reporter ions for classification and collision-induced dissociation (CID) to generate unique fragmentation spectra for isomeric variants of previously unreported species. Ellagitannin anions efficiently form three characteristic reporter ions after HCD fragmentation that allows for the classification of unknown precursors that we call targeted reporter ion triggering (TRT). We demonstrate how a tandem HCD-CID experiment might be used to screen natural sources using UHPLC-MS/MS by application of 22 method conditions from which an optimized data-dependent acquisition (DDA) emerged. The method was verified not to yield false-positive results in complex plant matrices. We were able to identify 154 non-isomeric ellagitannins from strawberry leaves, which is 17 times higher than previously reported in the same matrix. The systematic inclusion of CID spectra for isomers of each species classified as an ellagitannin has never been possible before the development of this approach

Les ascopyrones P et T: deux nouveaux composés issus du métabolisme d’ascomycétes “activés”

When subjected to 'activating' plasrnolytic treatrnents, several Ascornycetes exhibit an enzyrnic activity which degrades 1,4-α-D-glucans to 1,5-D-anhydrofructose, then converts this sugar to ascopyrone P (in Pezizales) or ascopyrone T (in TuberaJes). Biogenetical, rnycological and practical implications of these bioconversions are discussed

Les ascopyrones P et T: deux nouveaux composés issus du métabolisme d’ascomycétes “activés”

When subjected to 'activating' plasrnolytic treatrnents, several Ascornycetes exhibit an enzyrnic activity which degrades 1,4-α-D-glucans to 1,5-D-anhydrofructose, then converts this sugar to ascopyrone P (in Pezizales) or ascopyrone T (in TuberaJes). Biogenetical, rnycological and practical implications of these bioconversions are discussed

Activation of the striated urethral sphincter to maintain continence during dynamic tasks in healthy men

Aims Function of the striated urethral sphincter (SUS) in men is debated. Current evidence is limited to electromyographic (EMG) recordings made with concentric needle electrodes in supine. Understanding of SUS function requires investigation of SUS EMG activity using new recording techniques in dynamic tasks. The aim of this study was to evaluate timing and amplitude of SUS EMG at rest and during dynamic tasks that challenge continence by increasing intra‐abdominal pressure (IAP). Methods Investigative study of five healthy men aged 25–39 years. Measurements included SUS, anal sphincter (AS), and transversus abdominus (TrA) EMG, and IAP (recorded with a nasogastric pressure catheter). Participants performed four tasks that challenged postural control in standing (single and repetitive arm movement, stepping and load catching). Results IAP amplitude and SUS activity were linearly correlated during repetitive arm movement (R 2 : 0.67–0.88). During stepping SUS EMG onset preceded the IAP increase, but followed it with rapid arm movements. When the trunk was loaded unpredictably onset of SUS generally followed the increase in IAP. The modest sample size meant only younger men were tested. Future studies might investigate healthy older men or those with certain pathologies. Conclusions Data show that SUS activity increases proportionally with IAP. This provided evidence that SUS contributes to continence when IAP is increased, and that postural control of the trunk involves activation of this muscle. Neurourol. Urodynam. 31:36–43, 2012. © 2011 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90400/1/21178_ftp.pd