The thyroid hormone system disrupting potential of resorcinol in fish.

Environmental pollutants capable of interfering with the thyroid hormone (TH) system increasingly raise concern for both human and environmental health. Recently, resorcinol has received attention as a compound of concern due to its endocrine disrupting properties. It is a known inhibitor of thyroperoxidase (TPO), an enzyme required in TH synthesis, and therapeutic use of resorcinol exposure has led to hypothyroidism in humans.

Examining effects of a novel estrogenic perfluoro-alcohol, 1H,1H,8H,8H-Perfluorooctane-1,8-diol (FC8-diol), using the fathead minnow EcoToxChip.

In a previous in vivo study, adult male fathead minnows (Pimephales promelas) were exposed via water for 4 days to 1H,1H,8H,8H-perfluorooctane-1,8-diol (FC8-diol). The present study expands on the evaluation of molecular responses to this perfluoro-alcohol by analyzing 26 male fathead minnow liver RNA samples from that study (five from each test concentration: 0, 0.018, 0.

Functional diversity of dopamine axons in prefrontal cortex during classical conditioning.

Midbrain dopamine neurons impact neural processing in the prefrontal cortex (PFC) through mesocortical projections. However, the signals conveyed by dopamine projections to the PFC remain unclear, particularly at the single-axon level. Here, we investigated dopaminergic axonal activity in the medial PFC (mPFC) during reward and aversive processing.

Comparing Transcriptomic Points of Departure to Apical Effect Concentrations For Larval Fathead Minnow Exposed to Chemicals with Four Different Modes Of Action.

It is postulated that below a transcriptomic-based point of departure, adverse effects are unlikely to occur, thereby providing a chemical concentration to use in screening level hazard assessment. The present study extends previous work describing a high-throughput fathead minnow assay that can provide full transcriptomic data after exposure to a test chemical. One-day post-hatch fathead minnows were exposed to ten concentrations of three representatives of four chemical modes of action: organophosphates, ecdysone receptor agonists, plant photosystem II inhibitors, and estrogen receptor agonists for 24 h.

Encoding of self-initiated actions in axon terminals of the mesocortical pathway.

Significance: The initiation of goal-directed actions is a complex process involving the medial prefrontal cortex and dopaminergic inputs through the mesocortical pathway. However, it is unclear what information the mesocortical pathway conveys and how it impacts action initiation. In this study, we unveiled the indispensable role of mesocortical axon terminals in encoding the execution of movements in self-initiated actions.

Evaluating potential developmental toxicity of perfluoroalkyl and polyfluoroalkyl substances in Xenopus laevis embryos and larvae.

As part of the US Environmental Protection Agency's perfluoroalkyl and polyfluoroalkyl substances (PFAS) Action Plan, the agency is committed to increasing our understanding of the potential ecological effects of PFAS. The objective of these studies was to examine the developmental toxicity of PFAS using the laboratory model amphibian species Xenopus laevis. We had two primary aims: (1) to understand the developmental toxicity of a structurally diverse set of PFAS compounds in developing embryos and (2) to characterize the potential impacts of perfluorooctanesulfonic acid (PFOS), perfluorohexanesulfonic acid (PFHxS), perfluorooctanoic acid (PFOA), and hexafluoropropylene oxide-dimer acid (HFPO-DA a.

Transcriptomics-Based Points of Departure for Daphnia magna Exposed to 18 Per- and Polyfluoroalkyl Substances.

Per- and polyfluoroalkyl substances (PFAS) represent a large group of contaminants of concern based on their widespread use, environmental persistence, and potential toxicity. Many traditional models for estimating toxicity, bioaccumulation, and other toxicological properties are not well suited for PFAS. Consequently, there is a need to generate hazard information for PFAS in an efficient and cost-effective manner.

Derivation of Transcriptomics-Based Points of Departure for 20 Per- or Polyfluoroalkyl Substances Using a Larval Fathead Minnow (Pimephales promelas) Reduced Transcriptome Assay.

Traditional toxicity testing has been unable to keep pace with the introduction of new chemicals into commerce. Consequently, there are limited or no toxicity data for many chemicals to which fish and wildlife may be exposed. Per- and polyfluoroalkyl substances (PFAS) are emblematic of this issue in that ecological hazards of most PFAS remain uncharacterized.

MOFganic Chemistry: Challenges and Opportunities for Metal-Organic Frameworks in Synthetic Organic Chemistry.

Metal-organic frameworks (MOFs) are porous, crystalline solids constructed from organic linkers and inorganic nodes that have been widely studied for applications in gas storage, chemical separations, and drug delivery. Owing to their highly modular structures and tunable pore environments, we propose that MOFs have significant untapped potential as catalysts and reagents relevant to the synthesis of next-generation therapeutics. Herein, we outline the properties of MOFs that make them promising for applications in synthetic organic chemistry, including new reactivity and selectivity, enhanced robustness, and user-friendly preparation.

Handling fluorinated gases as solid reagents using metal-organic frameworks.

Fluorine is an increasingly common substituent in pharmaceuticals and agrochemicals because it improves the bioavailability and metabolic stability of organic molecules. Fluorinated gases represent intuitive building blocks for the late-stage installation of fluorinated groups, but they are generally overlooked because they require the use of specialized equipment. We report a general strategy for handling fluorinated gases as benchtop-stable solid reagents using metal-organic frameworks (MOFs).

Measuring time use in rural India: Design and validation of a low-cost survey module.

Time use data facilitate understanding of labor supply, especially for women who often undertake unpaid care and home production. Although assisted diary-based time use surveys are suitable for low-literacy populations, they are costly and rarely used. We create a low-cost, scalable alternative that captures contextually-determined broad time categories; here, allocations across market work, household labor, and leisure.

Functional Diversity of Dopamine Axons in Prefrontal Cortex During Classical Conditioning.

Midbrain dopamine neurons impact neural processing in the prefrontal cortex (PFC) through mesocortical projections. However, the signals conveyed by dopamine projections to the PFC remain unclear, particularly at the single-axon level. Here, we investigated dopaminergic axonal activity in the medial PFC (mPFC) during reward and aversive processing.

Deiodinase inhibition impairs the formation of the three posterior swim bladder tissue layers during early embryonic development in zebrafish.

Thyroid hormone system disruption (THSD) negatively affects multiple developmental processes and organs. In fish, inhibition of deiodinases, which are enzymes crucial for (in)activating thyroid hormones (THs), leads to impaired swim bladder inflation. Until now, the underlying mechanism has remained largely unknown.

An optimized RNA extraction method for diverse leaves of Hawaiian , a hypervariable tree species complex.

Premise: The isolation of RNA from trees is challenging due to the interference of polyphenols and polysaccharides with downstream processes. Furthermore, many RNA extraction protocols are time consuming and involve hazardous chemicals. To address these issues, we aimed to develop a safe protocol for high-quality RNA extraction from diverse taxa representing a broad range of leaf toughness, pubescence, and secondary metabolites.

Foliar functional and genetic variation in a keystone Hawaiian tree species estimated through spectroscopy.

Imaging spectroscopy has the potential to map closely related plant taxa at landscape scales. Although spectral investigations at the leaf and canopy levels have revealed relationships between phylogeny and reflectance, understanding how spectra differ across, and are inherited from, genotypes of a single species has received less attention. We used a common-garden population of four varieties of the keystone canopy tree, Metrosideros polymorpha, from Hawaii Island and four F1-hybrid genotypes derived from controlled crosses to determine if reflectance spectra discriminate sympatric, conspecific varieties of this species and their hybrids.

Verification of In Vivo Estrogenic Activity for Four Per- and Polyfluoroalkyl Substances (PFAS) Identified as Estrogen Receptor Agonists via New Approach Methodologies.

Given concerns about potential toxicological hazards of the thousands of data-poor per- and polyfluorinated alkyl substances (PFAS) currently in commerce and detected in the environment, tiered testing strategies that employ high-throughput in vitro screening as an initial testing tier have been implemented. The present study evaluated the effectiveness of previous in vitro screening for identifying PFAS capable, or incapable, of inducing estrogenic responses in fish exposed in vivo. Fathead minnows () were exposed for 96 h to five PFAS (perfluorooctanoic acid [PFOA]; 1H,1H,8H,8H-perfluorooctane-1,8-diol [FC8-diol]; 1H,1H,10H,10H-perfluorodecane-1,10-diol [FC10-diol]; 1H,1H,8H,8H-perfluoro-3,6-dioxaoctane-1,8-diol [FC8-DOD]; and perfluoro-2-methyl-3-oxahexanoic acid [HFPO-DA]) that showed varying levels of in vitro estrogenic potency.

Machine learning makes magnificent macromolecules for medicine.

At the University of Minnesota, scientists explore the application of machine learning to screen a multiparametric library of polymers to investigate the relationship between polymer attributes, payload type, and biological outcomes to optimize polymeric vector development for delivery of nucleic acid payloads.

A Perspective on the History and Current Opportunities of Aqueous RAFT Polymerization.

Reversible addition-fragmentation chain transfer (RAFT) polymerization has proven itself as a powerful polymerization technique affording facile control of molecular weight, molecular weight distribution, architecture, and chain end groups - while maintaining a high level of tolerance for solvent and monomer functional groups. RAFT is highly suited to water as a polymerization solvent, with aqueous RAFT now utilized for applications such as controlled synthesis of ultra-high molecular weight polymers, polymerization induced self-assembly, and biocompatible polymerizations, among others. Water as a solvent represents a non-toxic, cheap, and environmentally friendly alternative to organic solvents traditionally utilized for polymerizations.

Chromosomal-level reference genome assembly of the North American wolverine (Gulo gulo luscus): a resource for conservation genomics.

We report a chromosomal-level genome assembly of a male North American wolverine (Gulo gulo luscus) from the Kugluktuk region of Nunavut, Canada. The genome was assembled directly from long-reads, comprising: 758 contigs with a contig N50 of 36.6 Mb; contig L50 of 20; base count of 2.

Malaria Box-Inspired Discovery of -Aminoalkyl-β-carboline-3-carboxamides, a Novel Orally Active Class of Antimalarials.

Virtual ligand screening of a publicly available database of antimalarial hits using a pharmacophore derived from antimalarial MMV008138 identified TCMDC-140230, a tetrahydro-β-carboline amide, as worthy of exploration. All four stereoisomers of this structure were synthesized, but none potently inhibited growth of the malaria parasite . Interestingly, , a minor byproduct of these syntheses, proved to be potent against and was orally efficacious (40 mg/kg) in an mouse model of malaria.

Barriers and Facilitators to Accessing Digital Health Tools Faced by South Asian Canadians in Surrey, British Columbia: Community-Based Participatory Action Exploration Using Photovoice.

Background: South Asian community members in Canada experience a higher burden of chronic disease than the general population. Digital health innovations provide a significant opportunity to address various health care challenges such as supporting patients in their disease self-management. However, South Asian community members are less likely to use digital tools for their health and face significant barriers in accessing them because of language or cultural factors.

Ancestral polymorphisms shape the adaptive radiation of across the Hawaiian Islands.

Some of the most spectacular adaptive radiations begin with founder populations on remote islands. How genetically limited founder populations give rise to the striking phenotypic and ecological diversity characteristic of adaptive radiations is a paradox of evolutionary biology. We conducted an evolutionary genomics analysis of genus , a landscape-dominant, incipient adaptive radiation of woody plants that spans a striking range of phenotypes and environments across the Hawaiian Islands.