A Unified Method for Oxidative and Reductive Decarboxylative Arylation with Orange Light-Driven Ir/Ni Metallaphotoredox Catalysis.

Carboxylic acids and their derivatives are powerful building blocks in dual Ir/Ni metallaphotoredox methods of decarboxylative arylation due to their abundance as feedstock compounds. However, the library of accessible carboxylic acids is limited by trends in radical stability, often necessitating the development of specific systems for challenging substrates. Herein, we disclose the application of a new Ir(III) photocatalyst and low-energy orange light Ir/Ni metallaphotoredox system with broad applicability in activating both native carboxylic acids and redox-active esters (RAEs).

Biochemical, molecular, and physiological assessments of crude oil dietary exposure in sub-adult red drum (Sciaenops ocellatus).

A 14-day exposure study in which sub-adult red drum (Sciaenops ocellatus) were fed a petroleum crude oil-treated pellet feed was conducted to assess the potential effects of ingesting an oil-contaminated food source. Though food consumption decreased, significant polycyclic aromatic hydrocarbons accumulated in the body and liver, which did not affect the body and liver's fatty acid composition. In the red drum given the crude oil-treated feed, a significant decrease in the RNA:DNA growth rate index was noted, while only subtle changes in body and liver lipid composition were seen.

Addressable superconductor integrated circuit memory from delay lines.

Recent advances in logic schemes and fabrication processes have renewed interest in using superconductor electronics for energy-efficient computing and quantum control processors. However, scalable superconducting memory still poses a challenge. To address this issue, we present an alternative to approaches that solely emphasize storage cell miniaturization by exploiting the minimal attenuation and dispersion properties of superconducting passive transmission lines to develop a delay-line memory system.

Orange Light-Driven C(sp)-C(sp) Cross-Coupling via Spin-Forbidden Ir(III) Metallaphotoredox Catalysis.

We report the development and characterization of a library of Ir(III) photocatalysts capable of undergoing spin-forbidden excitation (SFE) under orange light irradiation (595 nm). These catalysts were successfully applied to the construction of synthetically valuable C(sp)-C(sp) bonds inaccessible with existing methods of low-energy light-driven dual nickel/photoredox catalysis, demonstrating the synthetic utility of this photocatalyst family. The photocatalysts are capable of accessing both oxidatively and reductively activated coupling partners, illustrated through deaminative arylation and potassium alkyl trifluoroborate cross-coupling reactions with aryl halides.

Structure-activity relationship study of central pyridine-derived TYK2 JH2 inhibitors: Optimization of the PK profile through C4' and C6 variations.

Efforts directed at improving potency and preparing structurally different TYK2 JH2 inhibitors from the first generation of compounds such as 1a led to the SAR study of new central pyridyl based analogs 2-4. The current SAR study resulted in the identification of 4h as a potent and selective TYK2 JH2 inhibitor with distinct structural differences from 1a. In this manuscript, the in vitro and in vivo profiles of 4h are described.

Metallaphotoredox-Mediated Decarboxylative Cross-Coupling of α-Oxy Morpholine Carboxylic Acids and (Hetero)Aryl Halides.

A decarboxylative C(sp)-C(sp) cross-coupling reaction of α-oxy carboxylic acids using dual nickel/photoredox catalysis has been developed for the synthesis of complex morpholines and other saturated heterocycles, affording direct entry to scaffolds of interest in drug discovery. This chemistry can be applied to the coupling of an array of (hetero)aryl halides and α-heteroatom acids, providing C(sp)-C(sp)-coupled products in modest to excellent yields and enabling access to intermediates that can be further derivatized to multivector architectures.

Overcoming Photochemical Limitations in Metallaphotoredox Catalysis: Red-Light-Driven C-N Cross-Coupling.

Aryl amination is an essential transformation for medicinal, process, and materials chemistry. In addition to classic Buchwald-Hartwig amination conditions, blue-light-driven metallaphotoredox catalysis has emerged as a valuable tool for C-N cross-coupling. However, blue light suffers from low penetration through reaction media, limiting its scalability for industrial purposes.

Ni/Photoredox-Catalyzed C(sp)-C(sp) Cross-Coupling of Alkyl Pinacolboronates and (Hetero)Aryl Bromides.

Utilizing quinoline as a mild, catalytic additive, broadly applicable conditions for the Ni/photoredox-catalyzed C(sp)-C(sp) cross-coupling of (hetero)aryl bromides and alkyl pinacolboronate esters were developed, which can be applied to both batch and flow reactions. In addition to primary benzylic nucleophiles, both stabilized and nonstabilized secondary alkyl boronic esters are effective coupling partners. Density functional theory calculations suggest that alkyl radical generation occurs from an alkyl-B(pin)-quinoline complex, which may proceed via an energy transfer process.

Dispersed Crude Oil Induces Dysbiosis in the Red Snapper External Microbiota.

The fish external microbiota competitively excludes primary pathogens and prevents the proliferation of opportunists. A shift from healthy microbiota composition, known as dysbiosis, may be triggered by environmental stressors and increases host susceptibility to disease. The (DWH) oil spill was a significant stressor event in the Gulf of Mexico.

Characterization of the differential expressed genes and transcriptomic pathway analysis in the liver of sub-adult red drum (Sciaenops ocellatus) exposed to Deepwater Horizon chemically dispersed oil.

The Deepwater Horizon blowout resulted in the second-largest quantity of chemical dispersants used as a countermeasure for an open water oil spill in the Gulf of Mexico. Of which, the efficacy of dispersant as a mitigation strategy and its toxic effects on aquatic fauna remains controversial. To enhance our understanding of potential sub-lethal effects of exposure to chemically dispersed-oil, sub-adult red drum (Sciaenops ocellatus) were continuously exposed to a Corexit 9500: DWH crude oil chemically enhanced water accommodated fraction (CEWAF) for 3-days and transcriptomic responses were assessed in the liver.

The Development of Reaction Cascades to Synthesize Dimeric Coccinellid Alkaloids.

Over the course of the past decade, our group has been intensely interested in achieving the laboratory synthesis of varied members of the coccinellid alkaloid family of natural products. These compounds, produced by varied species of ladybugs throughout the world as defensive agents, include several polycyclic members that can formally be considered as either monomeric or dimeric with architectures that contain between 3 and 7 ring systems along with an array of stereocenters. As a result of their fascinating structures, many groups have achieved syntheses of varied monomeric members using a variety of synthetic strategies and tactics.

Characterizing transcriptomic responses of southern flounder (Paralichthys lethostigma) chronically exposed to Deepwater Horizon oiled sediments.

To obtain a deeper understanding of the transcriptomic responses to oil in southern flounder (Paralichthys lethostigma), we performed quantitative PCR and RNA sequencing on liver and gill tissue after a chronic exposure (35 days) to Deepwater Horizon crude oiled sediment and after a 30-day recovery period. We wanted to understand which specific genes are differentially expressed in liver and gill tissues directly after oiled sediment exposure and with the addition of a recovery period. Furthermore, we wanted to examine specific enriched pathways in these two tissues to determine the impact of exposure with and without a recovery period on biological processes (e.

Nonlethal Biomarkers of Oxidative Stress in Oiled Sediment Exposed Southern Flounder (): Utility for Field-Base Monitoring Exposure and Potential Recovery.

The Deepwater Horizon (DWH) blowout resulted in the deposition of toxic polycyclic aromatic hydrocarbons (PAHs), in the coastal sediments of the Gulf of Mexico. The immediate effects on an ecosystem from an oil spill are clearly recognizable, however the long-term chronic effects and recovery after a spill are still not well understood. Current methodologies for biomonitoring wild populations are invasive and mostly lethal.

Anti-Markovnikov Hydroamination of Unactivated Alkenes with Primary Alkyl Amines.

We report here a photocatalytic method for the intermolecular anti-Markovnikov hydroamination of unactivated olefins with primary alkyl amines to selectively furnish secondary amine products. These reactions proceed through aminium radical cation (ARC) intermediates and occur at room temperature under visible light irradiation in the presence of an iridium photocatalyst and an aryl thiol hydrogen atom donor. Despite the presence of excess olefin, high selectivities are observed for secondary over tertiary amine products, even though the secondary amines are established substrates for ARC-based olefin amination under similar conditions.

Catalytic Ring Expansions of Cyclic Alcohols Enabled by Proton-Coupled Electron Transfer.

We report here a catalytic method for the modular ring expansion of cyclic aliphatic alcohols. In this work, proton-coupled electron transfer activation of an allylic alcohol substrate affords an alkoxy radical intermediate that undergoes subsequent C-C bond cleavage to furnish an enone and a tethered alkyl radical. Recombination of this alkyl radical with the revealed olefin acceptor in turn produces a ring-expanded ketone product.

Decarboxylative Intramolecular Arene Alkylation Using N-(Acyloxy)phthalimides, an Organic Photocatalyst, and Visible Light.

An intramolecular arene alkylation reaction has been developed using the organic photocatalyst 4CzIPN, visible light, and N-(acyloxy)phthalimides as radical precursors. Reaction conditions were optimized via high-throughput experimentation, and electron-rich and electron-deficient arenes and heteroarenes are viable reaction substrates. This reaction enables access to a diverse set of fused, partially saturated cores which are of high interest in synthetic and medicinal chemistry.

De novo assembly and transcriptome dataset of liver, testis and head kidney from red drum ().

Red drum () is an estuarine Sciaenid with high commercial value and recreational demand. During the past 50 years, overfishing has caused declines in the population that resulted in the development of red drum commercial and stock enhancement aquaculture fisheries. Despite the potential high economic value in both wild and aquaculture commercial fisheries the availability of transcriptomic data for red drum in public databases is limited.

Organocatalyzed, Visible-Light Photoredox-Mediated, One-Pot Minisci Reaction Using Carboxylic Acids via N-(Acyloxy)phthalimides.

An improved, one-pot Minisci reaction has been developed using visible light, an organic photocatalyst, and carboxylic acids as radical precursors via the intermediacy of in situ-generated N-(acyloxy)phthalimides. The conditions employed are mild, demonstrate a high degree of functional group tolerance, and do not require a large excess of the carboxylic acid reactant. As a result, this reaction can be applied to drug-like scaffolds and molecules with sensitive functional groups, enabling late-stage functionalization, which is of high interest to medicinal chemistry.

Catalytic intermolecular hydroaminations of unactivated olefins with secondary alkyl amines.

The intermolecular hydroamination of unactivated alkenes with simple dialkyl amines remains an unsolved problem in organic synthesis. We report a catalytic protocol for efficient additions of cyclic and acyclic secondary alkyl amines to a wide range of alkyl olefins with complete anti-Markovnikov regioselectivity. In this process, carbon-nitrogen bond formation proceeds through a key aminium radical cation intermediate that is generated via electron transfer between an excited-state iridium photocatalyst and an amine substrate.

Linkage Mapping and Comparative Genomics of Red Drum () Using Next-Generation Sequencing.

Developments in next-generation sequencing allow genotyping of thousands of genetic markers across hundreds of individuals in a cost-effective manner. Because of this, it is now possible to rapidly produce dense genetic linkage maps for nonmodel species. Here, we report a dense genetic linkage map for red drum, a marine fish species of considerable economic importance in the southeastern United States and elsewhere.

Oligodendrocytes contribute to motor neuron death in ALS via SOD1-dependent mechanism.

Oligodendrocytes have recently been implicated in the pathophysiology of amyotrophic lateral sclerosis (ALS). Here we show that, in vitro, mutant superoxide dismutase 1 (SOD1) mouse oligodendrocytes induce WT motor neuron (MN) hyperexcitability and death. Moreover, we efficiently derived human oligodendrocytes from a large number of controls and patients with sporadic and familial ALS, using two different reprogramming methods.

Deterministic transfection drives efficient nonviral reprogramming and uncovers reprogramming barriers.

Unlabelled: Safety concerns and/or the stochastic nature of current transduction approaches have hampered nuclear reprogramming's clinical translation. We report a novel non-viral nanotechnology-based platform permitting deterministic large-scale transfection with single-cell resolution. The superior capabilities of our technology are demonstrated by modification of the well-established direct neuronal reprogramming paradigm using overexpression of the transcription factors Brn2, Ascl1, and Myt1l (BAM).

Primary cilia enhance kisspeptin receptor signaling on gonadotropin-releasing hormone neurons.

Most central neurons in the mammalian brain possess an appendage called a primary cilium that projects from the soma into the extracellular space. The importance of these organelles is highlighted by the fact that primary cilia dysfunction is associated with numerous neuropathologies, including hyperphagia-induced obesity, hypogonadism, and learning and memory deficits. Neuronal cilia are enriched for signaling molecules, including certain G protein-coupled receptors (GPCRs), suggesting that neuronal cilia sense and respond to neuromodulators in the extracellular space.

A strategy for complex dimer formation when biomimicry fails: total synthesis of ten coccinellid alkaloids.

Although dimeric natural products can often be synthesized in the laboratory by directly merging advanced monomers, these approaches sometimes fail, leading instead to non-natural architectures via incorrect unions. Such a situation arose during our studies of the coccinellid alkaloids, when attempts to directly dimerize Nature's presumed monomeric precursors in a putative biomimetic sequence afforded only a non-natural analogue through improper regiocontrol. Herein, we outline a unique strategy for dimer formation that obviates these difficulties, one which rapidly constructs the coccinellid dimers psylloborine A and isopsylloborine A through a terminating sequence of two reaction cascades that generate five bonds, five rings, and four stereocenters.

Free-standing carbon nanotube/graphene hybrid papers as next generation adsorbents.

The adsorption of a series of aromatic compounds from aqueous solution onto purified, free-standing single-walled carbon nanotube/graphene nanoplatelet hybrid papers is studied both experimentally and theoretically. Experimental data is obtained via changes in optical absorption spectra of the aqueous solutions and is used to extract all parameters required to implement a semi-empirical mass-transfer model. Agreement between experiment and theory is excellent and data from all compounds can be cast on a universal adsorption curve.