HATRIC-based identification of receptors for orphan ligands

Technologies for identifying receptor-ligand pairs on living cells at physiological conditions remain scarce. Here, the authors develop a mass spectrometry-based ligand receptor capture technology that can identify receptors for a diverse range of ligands at physiological pH with as few as a million cells

Re-Infection Outcomes following One- and Two-Stage Surgical Revision of Infected Hip Prosthesis:A Systematic Review and Meta-Analysis

The two-stage revision strategy has been claimed as being the "gold standard" for treating prosthetic joint infection. The one-stage revision strategy remains an attractive alternative option; however, its effectiveness in comparison to the two-stage strategy remains uncertain.To compare the effectiveness of one- and two-stage revision strategies in treating prosthetic hip infection, using re-infection as an outcome.Systematic review and meta-analysis.MEDLINE, EMBASE, Web of Science, Cochrane Library, manual search of bibliographies to March 2015, and email contact with investigators.Cohort studies (prospective or retrospective) conducted in generally unselected patients with prosthetic hip infection treated exclusively by one- or two-stage revision and with re-infection outcomes reported within two years of revision. No clinical trials were identified.Data were extracted by two independent investigators and a consensus was reached with involvement of a third. Rates of re-infection from 38 one-stage studies (2,536 participants) and 60 two-stage studies (3,288 participants) were aggregated using random-effect models after arcsine transformation, and were grouped by study and population level characteristics.In one-stage studies, the rate (95% confidence intervals) of re-infection was 8.2% (6.0-10.8). The corresponding re-infection rate after two-stage revision was 7.9% (6.2-9.7). Re-infection rates remained generally similar when grouped by several study and population level characteristics. There was no strong evidence of publication bias among contributing studies.Evidence from aggregate published data suggest similar re-infection rates after one- or two-stage revision among unselected patients. More detailed analyses under a broader range of circumstances and exploration of other sources of heterogeneity will require collaborative pooling of individual participant data.PROSPERO 2015: CRD42015016559

Enantioselective Iridium-Catalyzed Allylic Cyclizations

ISSN:1523-7060ISSN:1523-705

Amine-Selective Bioconjugation Using Arene Diazonium Salts

A novel bioconjugation strategy is presented that relies on the coupling of diazonium terephthalates with amines in proteins. The diazonium captures the amine while the vicinal ester locks it through cyclization, ensuring no reversibility. The reaction is highly efficient and proceeds under mild conditions and short reaction times. Densely functionalized, complex natural products were directly coupled to proteins using low concentrations of coupling partners

Iridium-Catalyzed Enantioselective Polyene Cyclization

A highly enantioselective polycyclization method has been developed using the combination of Lewis acid activation with iridium-catalyzed allylic substitution. This strategy relies on direct use of branched, racemic allylic alcohols and furnishes a diverse and unique set of carbo- and heteropolycyclic ring systems in good yields and ≥99% ee

Enantioselective Iridium-Catalyzed Allylic Cyclizations

A method for the enantioselective synthesis of carbo- and heterocyclic ring systems enabled through the combination of Lewis acid activation and iridium-catalyzed allylic substitution is described. The reaction proceeds with branched, allylic alcohols and carbon nucleophiles as well as heteronucleophiles to give a diverse set of ring systems in good yields and with high enantioselectivities. The utility of the method is highlighted by the asymmetric syntheses of erythrococcamides A and B

Δ9-cis-Tetrahydrocannabinol: Natural Occurrence, Chirality, and Pharmacology.

The cis-stereoisomers of Δ9-THC [(-)-3 and (+)-3] were identified and quantified in a series of low-THC-containing varieties of Cannabis sativa registered in Europe as fiber hemp and in research accessions of cannabis. While Δ9-cis-THC (3) occurs in cannabis fiber hemp in the concentration range of (-)-Δ9-trans-THC [(-)-1], it was undetectable in a sample of high-THC-containing medicinal cannabis. Natural Δ9-cis-THC (3) is scalemic (ca. 80-90% enantiomeric purity), and the absolute configuration of the major enantiomer was established as 6aS,10aR [(-)-3] by chiral chromatographic comparison with a sample available by asymmetric synthesis. The major enantiomer, (-)-Δ9-cis-THC [(-)-3], was characterized as a partial cannabinoid agonist in vitro and elicited a full tetrad response in mice at 50 mg/kg doses. The current legal discrimination between narcotic and non-narcotic cannabis varieties centers on the contents of "Δ9-THC and isomers" and needs therefore revision, or at least a more specific wording, to account for the presence of Δ9-cis-THCs [(+)-3 and (-)-3] in cannabis fiber hemp varieties

The effect of a crosslinking chemical reaction on pattern formation in viscous fingering of miscible fluids in a Hele–Shaw cell

Viscous fingering can occur in fluid motion whenever a high mobility fluid displaces a low mobility fluid in a Darcy type flow. When the mobility difference is primarily attributable to viscosity (e.g., flow between the two horizontal plates of a Hele-Shaw cell), viscous fingering (VF) occurs, which is sometimes termed the Saffman-Taylor instability. Alternatively, in the presence of differences in density in a gravity field, buoyancy-driven convection can occur. These instabilities have been studied for decades, in part because of their many applications in pollutant dispersal, ocean currents, enhanced petroleum recovery, and so on. More recent interest has emerged regarding the effects of chemical reactions on fingering instabilities. As chemical reactions change the key flow parameters (densities, viscosities, and concentrations), they may have either a destabilizing or stabilizing effect on the flow. Hence, new flow patterns can emerge; moreover, one can then hope to gain some control over flow instabilities through reaction rates, flow rates, and reaction products. We report effects of chemical reactions on VF in a Hele-Shaw cell for a reactive step-growth cross-linking polymerization system. The cross-linked reaction product results in a non-monotonic viscosity profile at the interface, which affects flow stability. Furthermore, three-dimensional internal flows influence the long-term pattern that results

Design, Synthesis, and Evaluation of 18F‑Labeled Monoacylglycerol Lipase Inhibitors as Novel Positron Emission Tomography Probes

Dysfunction of monoacylglycerol lipase (MAGL) is associated with severalpsychopathological disorders, including drug addiction and neurodegenerative diseases. Herein we design, synthesize, and evaluate several irreversible fluorine-containing MAGL inhibitors for positron emission tomography (PET) ligand development. Compound 6 (identified from a therapeutic agent) was advanced for 18F-labeling via a novel spirocyclic iodonium ylide (SCIDY) strategy, which demonstrated high brain permeability and excellent specific binding. This work supports further development of novel 18F-labeled MAGL PET probes

Synthesis of Photoswitchable Δ⁹‑Tetrahydrocannabinol Derivatives Enables Optical Control of Cannabinoid Receptor 1 Signaling

The cannabinoid receptor 1 (CB1) is an inhibitory G protein-coupled receptor abundantly expressed in the central nervous system. It has rich pharmacology and largely accounts for the recreational use of cannabis. We describe efficient asymmetric syntheses of four photoswitchable Δ⁹-tetrahydrocannabinol derivatives (<i>azo</i>-THCs) from a central building block <b>3-Br-THC</b>. Using electrophysiology and a FRET-based cAMP assay, two compounds are identified as potent CB1 agonists that change their effect upon illumination. As such, <i>azo</i>-THCs enable CB1-mediated optical control of inwardly rectifying potassium channels, as well as adenylyl cyclase