Final CONUS Results on Coherent Elastic Neutrino-Nucleus Scattering at the Brokdorf Reactor.

The CONUS experiment studies coherent elastic neutrino-nucleus scattering in four 1 kg germanium spectrometers. Low ionization energy thresholds of 210 eV were achieved. The detectors were operated inside an optimized shield at the Brokdorf nuclear power plant which provided a reactor antineutrino flux of up to 2.

Pharmacological restriction of genomic binding sites redirects PU.1 pioneer transcription factor activity.

Transcription factor (TF) DNA-binding dynamics govern cell fate and identity. However, our ability to pharmacologically control TF localization is limited. Here we leverage chemically driven binding site restriction leading to robust and DNA-sequence-specific redistribution of PU.

Spns1 is an iron transporter essential for megalin-dependent endocytosis.

Proximal tubule endocytosis is essential to produce protein-free urine as well as to regulate system-wide metabolic pathways, such as the activation of Vitamin D. We have determined that the proximal tubule expresses an endolysosomal membrane protein, protein spinster homolog1 (Spns1), which engenders a novel iron conductance that is indispensable during embryonic development. Conditional knockout of Spns1 with a novel Cre-LoxP construct specific to megalin-expressing cells led to the arrest of megalin receptor-mediated endocytosis as well as dextran pinocytosis in proximal tubules.

Tailoring Metallosupramolecular Glycoassemblies for Enhancing Lectin Recognition.

Multivalency is a fundamental principle in nature that leads to high-affinity intermolecular recognition through multiple cooperative interactions that overcome the weak binding of individual constituents. For example, multivalency plays a critical role in lectin-carbohydrate interactions that participate in many essential biological processes. Designing high-affinity multivalent glycoconjugates that engage lectins results in systems with the potential to disrupt these biological processes, offering promising applications in therapeutic design and bioengineering.

Implementation of the CREED approach for environmental assessments.

Environmental exposure data are a key component of chemical and ecological assessments, supporting and guiding environmental management decisions and regulations. Measures taken to protect the environment based on exposure data can have social and economic implications. Flawed information may lead to measures being taken in the wrong place or to important action not being taken.

Incorporating climate change model projections into ecological risk assessments to help inform risk management and adaptation strategies: Synthesis of a SETAC Pellston Workshop®.

The impacts of global climate change are not yet well integrated with the estimates of the impacts of chemicals on the environment. This is evidenced by the lack of consideration in national or international reports that evaluate the impacts of climate change and chemicals on ecosystems and the relatively few peer-reviewed publications that have focused on this interaction. In response, a 2011 Pellston Workshop® was held on this issue and resulted in seven publications in Environmental Toxicology and Chemistry.

Integrating climate model projections into environmental risk assessment: A probabilistic modeling approach.

The Society of Environmental Toxicology and Chemistry (SETAC) convened a Pellston workshop in 2022 to examine how information on climate change could be better incorporated into the ecological risk assessment (ERA) process for chemicals as well as other environmental stressors. A major impetus for this workshop is that climate change can affect components of ecological risks in multiple direct and indirect ways, including the use patterns and environmental exposure pathways of chemical stressors such as pesticides, the toxicity of chemicals in receiving environments, and the vulnerability of species of concern related to habitat quality and use. This article explores a modeling approach for integrating climate model projections into the assessment of near- and long-term ecological risks, developed in collaboration with climate scientists.

Evaluating the effects of climate change and chemical, physical, and biological stressors on nearshore coral reefs: A case study in the Great Barrier Reef, Australia.

An understanding of the combined effects of climate change (CC) and other anthropogenic stressors, such as chemical exposures, is essential for improving ecological risk assessments of vulnerable ecosystems. In the Great Barrier Reef, coral reefs are under increasingly severe duress from increasing ocean temperatures, acidification, and cyclone intensities associated with CC. In addition to these stressors, inshore reef systems, such as the Mackay-Whitsunday coastal zone, are being impacted by other anthropogenic stressors, including chemical, nutrient, and sediment exposures related to more intense rainfall events that increase the catchment runoff of contaminated waters.

Development and Validation of Multiple Linear Regression Models for Predicting Chronic Zinc Toxicity to Freshwater Microalgae.

Multiple linear regression (MLR) models were developed for predicting chronic zinc toxicity to a freshwater microalga, Chlorella sp., using three toxicity-modifying factors (TMFs): pH, hardness, and dissolved organic carbon (DOC). The interactive effects between pH and hardness and between pH and DOC were also included.

Applicability of Chronic Multiple Linear Regression Models for Predicting Zinc Toxicity in Australian and New Zealand Freshwaters.

Bioavailability models, for example, multiple linear regressions (MLRs) of water quality parameters, are increasingly being used to develop bioavailability-based water quality criteria for metals. However, models developed for the Northern Hemisphere cannot be adopted for Australia and New Zealand without first validating them against local species and local water chemistry characteristics. We investigated the applicability of zinc chronic bioavailability models to predict toxicity in a range of uncontaminated natural waters in Australia and New Zealand.

Acute and chronic toxicity of manganese to tropical adult coral (Acropora millepora) to support the derivation of marine manganese water quality guideline values.

Adult corals are among the most sensitive marine organisms to dissolved manganese and experience tissue sloughing without bleaching (i.e., no loss of Symbiodinium spp.

Adult Corals Are Uniquely More Sensitive to Manganese Than Coral Early-Life Stages.

Manganese (Mn) is an essential element and is generally considered to be one of the least toxic metals to aquatic organisms, with chronic effects rarely seen at concentrations below 1000 µg/L. Anthropogenic activities lead to elevated concentrations of Mn in tropical marine waters. Limited data suggest that Mn is more acutely toxic to adults than to early life stages of scleractinian corals in static renewal tests.

The Effects of Nickel and Copper on Tropical Marine and Freshwater Microalgae Using Single and Multispecies Tests.

Microalgae are key components of aquatic food chains and are known to be sensitive to a range of contaminants. Much of the available data on metal toxicity to microalgae have been derived from temperate single-species tests with temperate data used to supplement tropical toxicity data sets to derive guideline values. In the present study, we used single-species and multispecies tests to investigate the toxicity of nickel and copper to tropical freshwater and marine microalgae, including the free-swimming stage of Symbiodinium sp.

Programmable synthesis of well-defined, glycosylated iron(ii) supramolecular assemblies with multivalent protein-binding capabilities.

Multivalency plays a key role in achieving strong, yet reversible interactions in nature, and provides critical chemical organization in biological recognition processes. Chemists have taken an interest in designing multivalent synthetic assemblies to both better understand the underlying principles governing these interactions, and to build chemical tools that either enhance or prevent such recognition events from occurring in biology. Rationally tailoring synthetic strategies to achieve the high level of chemical control and tunability required to mimic these interactions, however, is challenging.

Natural organic matter source, concentration, and pH influences the toxicity of zinc to a freshwater microalga.

Zinc is a contaminant of concern in aquatic environments and is a known toxicant to many aquatic organisms. Dissolved organic matter (DOM) is a toxicity modifying factor for zinc and is an important water chemistry parameter. This study investigated the influence of DOM concentration, source, and water pH on the chronic toxicity of zinc to a freshwater microalga, Chlorella sp.

Tumor Distribution by Quantitative Mass Spectrometry Imaging of the Inhibitor of Apoptosis Protein Antagonist Xevinapant in Patients with Resectable Squamous Cell Carcinoma of the Head and Neck (EudraCT Number: 2014-004655-31).

As tumors are very heterogeneous, investigating the penetration and concentration of an anticancer drug in different histological regions of a tumor is key to evaluate the efficacy, to improve the pharmacokinetics/pharmacodynamics (PK/PD) relationship evaluation, and to confirm the adequacy of the dose regimen. Quantitative mass spectrometry imaging (QMSI) allows for the determination of the tissue distribution of drugs, metabolites, and biomarkers to support quick and precise evaluation of drug efficacy and safety in a single experiment. QMSI was applied in a preoperative window-of-opportunity (WoO) study of the inhibitor of apoptosis protein antagonist xevinapant (Debio 1143) in patients with resectable squamous cell carcinoma of the head and neck (SCCHN).

A generic environmental risk assessment framework for deep-sea tailings placement.

Deep-sea tailings placement (DSTP) involves the oceanic discharge of tailings at depth (usually >100 m), with the intent of ultimate deposition of tailings solids on the deep-sea bed (>1000 m), well below the euphotic zone. DSTP discharges consist of a slurry of mine tailings solids (finely crushed rock) and residual process liquor containing low concentrations of metals, metalloids, flotation agents and flocculants. This slurry can potentially affect both pelagic and benthic biota inhabiting coastal waters, the continental slope and the deep-sea bed.

An Organometallic Gold(III) Reagent for F Labeling of Unprotected Peptides and Sugars in Aqueous Media.

The F labeling of unprotected peptides and sugars with a Au(III)-[F]fluoroaryl complex is reported. The chemoselective method generates F-labeled -aryl bioconjugates in an aqueous environment in 15 min with high radiochemical yields and displays excellent functional group tolerance. This approach utilizes an air and moisture stable, robust organometallic Au(III) complex and highlights the versatility of designer organometallic reagents as efficient agents for rapid radiolabeling.

Hyaluronic acid detection and relative quantification by mass spectrometry imaging in human skin tissues.

Hyaluronic acid (HA) is a major component of the skin, contributing to tissue hydration and biomechanical properties. As HA content in the skin decreases with age, formulas containing HA are widely used in cosmetics and HA injections in aesthetic procedures to reduce the signs of aging. To prove the beneficial effects of these treatments, efficient quantification of HA levels in the skin is necessary, but remains difficult.

Caffeine intake exerts dual genome-wide effects on hippocampal metabolism and learning-dependent transcription.

Caffeine is the most widely consumed psychoactive substance in the world. Strikingly, the molecular pathways engaged by its regular consumption remain unclear. We herein addressed the mechanisms associated with habitual (chronic) caffeine consumption in the mouse hippocampus using untargeted orthogonal omics techniques.

The influence of hardness at varying pH on zinc toxicity and lability to a freshwater microalga, sp.

Zinc is an essential element for aquatic organisms, however, activities such as mining and refining, as well as zinc's ubiquitous role in modern society can contribute to elevated environmental concentrations of zinc. Water hardness is widely accepted as an important toxicity modifying factor for metals in aquatic systems, though other factors such as pH are also important. This study investigated the influence of increasing water hardness, at three different pH values (6.

Snapshots of nascent RNA reveal cell- and stimulus-specific responses to acute kidney injury.

The current strategy to detect acute injury of kidney tubular cells relies on changes in serum levels of creatinine. Yet serum creatinine (sCr) is a marker of both functional and pathological processes and does not adequately assay tubular injury. In addition, sCr may require days to reach diagnostic thresholds, yet tubular cells respond with programs of damage and repair within minutes or hours.

Sediment spiking and equilibration procedures to achieve partitioning of uranium similar to contamination in tropical wetlands near a mine site.

The derivation of sediment quality guideline values (SQGVs) presents significant challenges. Arguably the most important challenge is to conduct toxicity tests using contaminated sediments with physico-chemistry that represents real-world scenarios. We used a novel metal spiking method for an experiment that ultimately aims to derive a uranium SQGV.