Discovery of Latent Cannabichromene Cyclase Activity in Marine Bacterial Flavoenzymes.

Production of phytocannabinoids remains an area of active scientific interest due to the growing use of cannabis by the public and the underexplored therapeutic potential of the over 100 minor cannabinoids. While phytocannabinoids are biosynthesized by and other select plants and fungi, structural analogs and stereoisomers can only be accessed synthetically or through heterologous expression. To date, the bioproduction of cannabinoids has required eukaryotic hosts like yeast since key, native oxidative cyclization enzymes do not express well in bacterial hosts.

Antibacterial Marinopyrroles and Pseudilins Act as Protonophores.

Elucidating the mechanism of action (MoA) of antibacterial natural products is crucial to evaluating their potential as novel antibiotics. Marinopyrroles, pentachloropseudilin, and pentabromopseudilin are densely halogenated, hybrid pyrrole-phenol natural products with potent activity against Gram-positive bacterial pathogens like . However, the exact way they exert this antibacterial activity has not been established.

Linking bacterial tetrabromopyrrole biosynthesis to coral metamorphosis.

An important factor dictating coral fitness is the quality of bacteria associated with corals and coral reefs. One way that bacteria benefit corals is by stimulating the larval to juvenile life cycle transition of settlement and metamorphosis. Tetrabromopyrrole (TBP) is a small molecule produced by bacteria that stimulates metamorphosis with and without attachment in a range of coral species.

Linking bacterial tetrabromopyrrole biosynthesis to coral metamorphosis.

An important factor dictating coral fitness is the quality of bacteria associated with corals and coral reefs. One way that bacteria benefit corals is by stimulating the larval to juvenile life cycle transition of settlement and metamorphosis. Tetrabromopyrrole (TBP) is a small molecule produced by bacteria that stimulates metamorphosis in a range of coral species.

The Cyanobacterial "Nutraceutical" Phycocyanobilin Inhibits Cysteine Protease Legumain.

The blue biliprotein phycocyanin, produced by photo-autotrophic cyanobacteria including spirulina (Arthrospira) and marketed as a natural food supplement or "nutraceutical," is reported to have anti-inflammatory, antioxidant, immunomodulatory, and anticancer activity. These diverse biological activities have been specifically attributed to the phycocyanin chromophore, phycocyanobilin (PCB). However, the mechanism of action of PCB and the molecular targets responsible for the beneficial properties of PCB are not well understood.

Harnessing -Quinone Methides in Natural Product Biosynthesis and Biocatalysis.

The implementation of -quinone methide (-QM) intermediates in complex molecule assembly represents a remarkably efficient strategy designed by Nature and utilized by synthetic chemists. -QMs have been taken advantage of in biomimetic syntheses for decades, yet relatively few examples of QM-generating enzymes in natural product biosynthetic pathways have been reported. The biosynthetic enzymes that have been discovered thus far exhibit tremendous potential for biocatalytic applications, enabling the selective production of desirable compounds that are otherwise intractable or inherently difficult to achieve by traditional synthetic methods.

Marine and Anthropogenic Bromopyrroles Alter Cellular Ca Dynamics of Murine Cortical Neuronal Networks by Targeting the Ryanodine Receptor and Sarco/Endoplasmic Reticulum Ca-ATPase.

Bromopyrroles (BrPyr) are synthesized naturally by marine sponge symbionts and produced anthropogenically as byproducts of wastewater treatment. BrPyr interact with ryanodine receptors (RYRs) and sarco/endoplasmic reticulum (SR/ER) Ca-ATPase (SERCA). Influences of BrPyr on the neuronal network activity remain uncharted.

Discovery and Biosynthesis of Tetrachlorizine Reveals Enzymatic Benzylic Dehydrogenation via an -Quinone Methide.

-quinone methides (-QMs) are reactive intermediates in biosynthesis that give rise to a variety of intra- and intermolecular cyclization/addition products in bacteria, fungi, and plants. Herein, we report a new metabolic deviation of an -QM intermediate in a benzylic dehydrogenation reaction that links the newly described marine bacterial natural products dihydrotetrachlorizine and tetrachlorizine. We discovered these novel dichloropyrrole-containing compounds from actinomycete strain AJS-327 that unexpectedly harbors in its genome a biosynthetic gene cluster (BGC) of striking similarity to that of chlorizidine, another marine alkaloid bearing a different carbon skeleton.

Detecting Acoustic Blackbody Radiation with an Optomechanical Antenna.

Nanomechanical systems are generally embedded in a macroscopic environment where the sources of thermal noise are difficult to pinpoint. We engineer a silicon nitride membrane optomechanical resonator such that its thermal noise is acoustically driven by a spatially well-defined remote macroscopic bath. This bath acts as an acoustic blackbody emitting and absorbing acoustic radiation through the silicon substrate.

Genetic examination of the marine bacterium Pseudoalteromonas luteoviolacea and effects of its metamorphosis-inducing factors.

Pseudoalteromonas luteoviolacea is a globally distributed marine bacterium that stimulates the metamorphosis of marine animal larvae, an important bacteria-animal interaction that can promote the recruitment of animals to benthic ecosystems. Recently, different P. luteoviolacea isolates have been shown to produce two stimulatory factors that can induce tubeworm and coral metamorphosis; Metamorphosis-Associated Contractile structures (MACs) and tetrabromopyrrole (TBP) respectively.

Bacterial Tetrabromopyrrole Debrominase Shares a Reductive Dehalogenation Strategy with Human Thyroid Deiodinase.

Enzymatic dehalogenation is an important and well-studied biological process in both the detoxification and catabolism of small molecules, many of which are anthropogenic in origin. However, dedicated dehalogenation reactions that replace a halogen atom with a hydrogen are rare in the biosynthesis of natural products. In fact, the debrominase Bmp8 is the only known example.

Quantum-based vacuum metrology at NIST.

The measurement science in realizing and disseminating the unit for pressure in the International System of Units (SI), the pascal (Pa), has been the subject of much interest at NIST. Modern optical-based techniques for pascal metrology have been investigated, including multi-photon ionization and cavity ringdown spectroscopy. Work is ongoing to recast the pascal in terms of quantum properties and fundamental constants and in so doing, make vacuum metrology consistent with the global trend toward quantum-based metrology.

Towards Replacing Resistance Thermometry with Photonic Thermometry.

Resistance thermometry provides a time-tested method for taking temperature measurements that has been painstakingly developed over the last century. However, fundamental limits to resistance-based approaches along with a desire to reduce the cost of sensor ownership and increase sensor stability has produced considerable interest in developing photonic temperature sensors. Here we demonstrate that silicon photonic crystal cavity-based thermometers can measure temperature with uncertainities of 175 mK ( = 1), where uncertainties are dominated by ageing effects originating from the hysteresis in the device packaging materials.

Quantum correlations from a room-temperature optomechanical cavity.

The act of position measurement alters the motion of an object being measured. This quantum measurement backaction is typically much smaller than the thermal motion of a room-temperature object and thus difficult to observe. By shining laser light through a nanomechanical beam, we measure the beam's thermally driven vibrations and perturb its motion with optical force fluctuations at a level dictated by the Heisenberg measurement-disturbance uncertainty relation.

Cooling a Harmonic Oscillator by Optomechanical Modification of Its Bath.

Optomechanical systems show tremendous promise for the high-sensitivity sensing of forces and modification of mechanical properties via light. For example, similar to neutral atoms and trapped ions, laser cooling of mechanical motion by radiation pressure can take single mechanical modes to their ground state. Conventional optomechanical cooling is able to introduce an additional damping channel to mechanical motion while keeping its thermal noise at the same level, and, as a consequence, the effective temperature of the mechanical mode is lowered.

Mass Spectrometry-Based Visualization of Molecules Associated with Human Habitats.

The cars we drive, the homes we live in, the restaurants we visit, and the laboratories and offices we work in are all a part of the modern human habitat. Remarkably, little is known about the diversity of chemicals present in these environments and to what degree molecules from our bodies influence the built environment that surrounds us and vice versa. We therefore set out to visualize the chemical diversity of five built human habitats together with their occupants, to provide a snapshot of the various molecules to which humans are exposed on a daily basis.

Laser Cooling of a Micromechanical Membrane to the Quantum Backaction Limit.

The radiation pressure of light can act to damp and cool the vibrational motion of a mechanical resonator, but even if the light field has no thermal component, shot noise still sets a limit on the minimum phonon occupation. In optomechanical sideband cooling in a cavity, the finite off-resonant Stokes scattering defined by the cavity linewidth combined with shot noise fluctuations dictates a quantum backaction limit, analogous to the Doppler limit of atomic laser cooling. In our work, we sideband cool a micromechanical membrane resonator to the quantum backaction limit.

Being two is better than one-catalytic reductions with dendrimer encapsulated copper- and copper-cobalt-subnanoparticles.

Copper and copper-cobalt subnanoparticles have been synthesized using 4-carbomethoxypyrrolidone terminated PAMAM-dendrimers as templates. The metal particles were applied in catalytic reduction reactions. While Cu subnanoparticles were only capable of reducing conjugated double bonds, enhancing the Cu particles with Co led to a surprising increase in catalytic activity, reducing also isolated carbon double and triple bonds.

Observation of radiation pressure shot noise on a macroscopic object.

The quantum mechanics of position measurement of a macroscopic object is typically inaccessible because of strong coupling to the environment and classical noise. In this work, we monitor a mechanical resonator subject to an increasingly strong continuous position measurement and observe a quantum mechanical back-action force that rises in accordance with the Heisenberg uncertainty limit. For our optically based position measurements, the back-action takes the form of a fluctuating radiation pressure from the Poisson-distributed photons in the coherent measurement field, termed radiation pressure shot noise.

Non-classical light generated by quantum-noise-driven cavity optomechanics.

Optomechanical systems, in which light drives and is affected by the motion of a massive object, will comprise a new framework for nonlinear quantum optics, with applications ranging from the storage and transduction of quantum information to enhanced detection sensitivity in gravitational wave detectors. However, quantum optical effects in optomechanical systems have remained obscure, because their detection requires the object’s motion to be dominated by vacuum fluctuations in the optical radiation pressure; so far, direct observations have been stymied by technical and thermal noise. Here we report an implementation of cavity optomechanics using ultracold atoms in which the collective atomic motion is dominantly driven by quantum fluctuations in radiation pressure.

Identification of naturally occurring fatty acids of the myelin sheath that resolve neuroinflammation.

Lipids constitute 70% of the myelin sheath, and autoantibodies against lipids may contribute to the demyelination that characterizes multiple sclerosis (MS). We used lipid antigen microarrays and lipid mass spectrometry to identify bona fide lipid targets of the autoimmune response in MS brain, and an animal model of MS to explore the role of the identified lipids in autoimmune demyelination. We found that autoantibodies in MS target a phosphate group in phosphatidylserine and oxidized phosphatidylcholine derivatives.

Control of material damping in high-Q membrane microresonators.

We study the mechanical quality factors of bilayer aluminum-silicon-nitride membranes. By coating ultrahigh-Q Si(3)N(4) membranes with a more lossy metal, we can precisely measure the effect of material loss on Q's of tensioned resonator modes over a large range of frequencies. We develop a theoretical model that interprets our results and predicts the damping can be reduced significantly by patterning the metal film.

Tunable cavity optomechanics with ultracold atoms.

We present an atom-chip-based realization of quantum cavity optomechanics with cold atoms localized within a Fabry-Perot cavity. Effective subwavelength positioning of the atomic ensemble allows for tuning the linear and quadratic optomechanical coupling parameters, varying the sensitivity to the displacement and strain of a compressible gaseous medium. We observe effects of such tuning on cavity optical nonlinearity and optomechanical frequency shifts, providing their first characterization in the quadratic-coupling regime.

The impact of mass school immunization on school attendance.

The purpose of this study was to assess the impact a free, on-site influenza immunization program could have on attendance in Title 1 schools. Four Title 1 elementary schools participated in the study. Students at 2 schools were offered free FluMist immunizations on site, and students at 2 control schools were not.

Bose-Einstein condensation in a circular waveguide.

We have produced Bose-Einstein condensates in a ring-shaped magnetic waveguide. The few-millimeter diameter, nonzero-bias ring is formed from a time-averaged quadrupole ring. Condensates that propagate around the ring make several revolutions within the time it takes for them to expand to fill the ring.