Heterogeneous impacts of ocean thermal forcing on ice discharge from Greenland's peripheral tidewater glaciers over 2000-2021.

The Greenland Ice Sheet is losing mass at increasing rates. Substantial amounts of this mass loss occur by ice discharge which is influenced by ocean thermal forcing. The ice sheet is surrounded by thousands of peripheral, dynamically decoupled glaciers. The mass loss from these glaciers is disproportionately high considering their negligible share in Greenland' overall ice mass. We study the relevance of ocean thermal forcing for ice discharge evolution in the context of this contrasting behaviour. Our estimate of ice discharge from the peripheral tidewater glaciers yields a rather stable Greenland-wide mean of 5.40 ± 3.54 Gt a-1 over 2000-2021. The evolutions of ice discharge and ocean thermal forcing are heterogeneous around Greenland. We observe a significant sector-wide increase of ice discharge in the East and a significant sector-wide decrease in the Northeast. Ocean thermal forcing shows significant increases along the northern/eastern coast, while otherwise unchanged conditions or decreases prevail. For East Greenland, this implies a clear influence of ocean thermal forcing on ice discharge. Similarly, we find clear influences at peripheral tidewater glaciers with thick termini that are similar to ice sheet outlet glaciers. At the peripheral glaciers in Northeast Greenland ice discharge evolution opposes ocean thermal forcing for unknown reasons.

Emergence of common concepts, symmetries and conformity in agent groups-an information-theoretic model.

The paper studies principles behind structured, especially symmetric, representations through enforced inter-agent conformity. For this, we consider agents in a simple environment who extract individual representations of this environment through an information maximization principle. The representations obtained by different agents differ in general to some extent from each other. This gives rise to ambiguities in how the environment is represented by the different agents. Using a variant of the information bottleneck principle, we extract a 'common conceptualization' of the world for this group of agents. It turns out that the common conceptualization appears to capture much higher regularities or symmetries of the environment than the individual representations. We further formalize the notion of identifying symmetries in the environment both with respect to 'extrinsic' (birds-eye) operations on the environment as well as with respect to 'intrinsic' operations, i.e. subjective operations corresponding to the reconfiguration of the agent's embodiment. Remarkably, using the latter formalism, one can re-wire an agent to conform to the highly symmetric common conceptualization to a much higher degree than an unrefined agent; and that, without having to re-optimize the agent from scratch. In other words, one can 're-educate' an agent to conform to the de-individualized 'concept' of the agent group with comparatively little effort.

Exenatide once weekly for alcohol use disorder investigated in a randomized, placebo-controlled clinical trial.

BackgroundAlcohol use disorder (AUD) is a chronic, relapsing brain disorder that accounts for 5% of deaths annually, and there is an urgent need to develop new targets for therapeutic intervention. The glucagon-like peptide-1 (GLP-1) receptor agonist exenatide reduces alcohol consumption in rodents and nonhuman primates, but its efficacy in patients with AUD is unknown.MethodsIn a randomized, double-blinded, placebo-controlled clinical trial, treatment-seeking AUD patients were assigned to receive exenatide (2 mg subcutaneously) or placebo once weekly for 26 weeks, in addition to standard cognitive-behavioral therapy. The primary outcome was reduction in number of heavy drinking days. A subgroup also completed functional MRI (fMRI) and single-photon emission CT (SPECT) brain scans.ResultsA total of 127 patients were enrolled. Our data revealed that although exenatide did not significantly reduce the number of heavy drinking days compared with placebo, it significantly attenuated fMRI alcohol cue reactivity in the ventral striatum and septal area, which are crucial brain areas for drug reward and addiction. In addition, dopamine transporter availability was lower in the exenatide group compared with the placebo group. Exploratory analyses revealed that exenatide significantly reduced heavy drinking days and total alcohol intake in a subgroup of obese patients (BMI > 30 kg/m2). Adverse events were mainly gastrointestinal.ConclusionThis randomized controlled trial on the effects of a GLP-1 receptor agonist in AUD patients provides new important knowledge on the effects of GLP-1 receptor agonists as a novel treatment target in addiction.Trial registrationEudraCT: 2016-003343-11. ClinicalTrials.gov (NCT03232112).FundingNovavi Foundation; Research Foundation, Mental Health Services, Capital Region of Denmark; Research Foundation, Capital Region of Denmark; Ivan Nielsen Foundation; A.P. Moeller Foundation; Augustinus Foundation; Woerzner Foundation; Grosserer L.F. Foghts Foundation; Hartmann Foundation; Aase and Ejnar Danielsen Foundation; P.A. Messerschmidt and Wife Foundation; and Lundbeck Foundation.

Ultrasmall Manganese Ferrites for In Vivo Catalase Mimicking Activity and Multimodal Bioimaging.

Manganese ferrite nanoparticles display interesting features in bioimaging and catalytic therapies. They have been recently used in theranostics as contrast agents in magnetic resonance imaging (MRI), and as catalase-mimicking nanozymes for hypoxia alleviation. These promising applications encourage the development of novel synthetic procedures to enhance the bioimaging and catalytic properties of these nanomaterials simultaneously. Herein, a cost-efficient synthetic microwave method is developed to manufacture ultrasmall manganese ferrite nanoparticles as advanced multimodal contrast agents in MRI and positron emission tomography (PET), and improved nanozymes. Such a synthetic method allows doping ferrites with Mn in a wide stoichiometric range (Mnx Fe3-x O4 , 0.1 ≤ x ≤ 2.4), affording a library of nanoparticles with different magnetic relaxivities and catalytic properties. These tuned magnetic properties give rise to either positive or dual-mode MRI contrast agents. On the other hand, higher levels of Mn doping enhance the catalytic efficiency of the resulting nanozymes. Finally, through their intracellular catalase-mimicking activity, these ultrasmall manganese ferrite nanoparticles induce an unprecedented tumor growth inhibition in a breast cancer murine model. All of these results show the robust characteristics of these nanoparticles for nanobiotechnological applications.

Proinflammatory biomarkers are associated with prediabetes in patients with schizophrenia.

BACKGROUND: Treatment with antipsychotics is associated with an increased risk of type 2 diabetes mellitus (T2D), and increased levels of inflammatory biomarkers are present in patients with T2D. We previously demonstrated that the glucagon-like peptide-1 receptor agonist liraglutide significantly reduced glucometabolic disturbances and body weight in prediabetic, overweight/obese schizophrenia-spectrum disorder patients treated with clozapine or olanzapine. This study aims to assess the involvement of cytokines in the therapeutic effects of liraglutide. METHODS: Serum concentrations of 10 cytokines (interferon-γ [IFN-γ], tumor necrosis factor-α, interleukin 1ß [IL-1ß], IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, and IL-13) from fasting prediabetic and normal glucose-tolerant (NGT) patients with schizophrenia-spectrum disorders were measured using multiplexed immunoassays. Prediabetic patients were randomized to 16 weeks of treatment with liraglutide or placebo, and cytokines were measured again at the end of the treatment. RESULTS: IFN-γ (1.98 vs 1.17 pg/ml, P = .001), IL-4 (0.02 vs 0.01 pg/ml, P < .001), and IL-6 (0.73 vs 0.46 pg/ml, P < .001) were significantly higher in prediabetic (n = 77) vs NGT patients (n = 31). No significant changes in cytokine levels following treatment with liraglutide (n = 37) vs placebo (n = 40) were found. CONCLUSION: Prediabetic vs NGT patients with schizophrenia treated with clozapine or olanzapine had increased serum levels of several proinflammatory cytokines, further substantiating the link between inflammation and T2D. Treatment with liraglutide did not affect the investigated cytokines. Further testing of these findings in larger numbers of individuals is needed.

Boosting the Photoluminescent Properties of Protein-Stabilized Gold Nanoclusters through Protein Engineering.

This work reports on the use of protein engineering as a versatile tool to rationally design metal-binding proteins for the synthesis of highly photoluminescent protein-stabilized gold nanoclusters (Prot-AuNCs). The use of a single repeat protein scaffold allowed the incorporation of a set of designed metal-binding sites to understand the effect of the metal-coordinating residues and the protein environment on the photoluminescent (PL) properties of gold nanoclusters (AuNCs). The resulting Prot-AuNCs, synthesized by two sustainable procedures, showed size-tunable color emission and outstanding PL properties. In a second stage, tryptophan (Trp) residues were introduced at specific positions to provide an electron-rich protein environment and favor energy transfer from Trps to AuNCs. This modification resulted in improved PL properties relevant for future applications in sensing, biological labeling, catalysis, and optics.

Antibody-Directed Synthesis of Catalytic Nanoclusters for Bioanalytical Assays.

Synthesis of atomic nanoclusters (NCs) using proteins as a scaffold has attracted great attention. Usually, the synthetic conditions for the synthesis of NCs stabilized with proteins require extreme pH values or temperature. These harsh reaction conditions cause the denaturation of the proteins and end up in the loss of their biological functions. Until now, there are no examples of the use of antibodies as NC stabilizers. In this work, we present the first method for the synthesis of catalytic NCs that uses antibodies for the stabilization of NCs. Anti-BSA IgG was used as a model to demonstrate that it is possible to use an antibody as a scaffold for the synthesis of semiconductor and metallic NCs with catalytic properties. The synthesis of antibodies modified with NCs is carried out under nondenaturing conditions, which do not affect the antibody structure. The resulting antibodies still maintain the affinity for target antigens and protein G. The catalytic properties of the anti-BSA IgG modified with NCs can be used to the quantification of bovine serum albumin (BSA) in a direct sandwich enzyme-linked immunosorbent assay (ELISA).

A Simple Approach to Design Proteins for the Sustainable Synthesis of Metal Nanoclusters.

Metal nanoclusters (NCs) are considered ideal nanomaterials for biological applications owing to their strong photoluminescence (PL), excellent photostability, and good biocompatibility. This study presents a simple and versatile strategy to design proteins, via incorporation of a di-histidine cluster coordination site, for the sustainable synthesis and stabilization of metal NCs with different metal composition. The resulting protein-stabilized metal NCs (Prot-NCs) of gold, silver, and copper are highly photoluminescent and photostable, have a long shelf life, and are stable under physiological conditions. The biocompatibility of the clusters was demonstrated in cell cultures in which Prot-NCs showed efficient cell internalization without affecting cell viability or losing luminescence. Moreover, the approach is translatable to other proteins to obtain Prot-NCs for various biomedical applications such as cell imaging or labeling.

Specific bioanalytical optical and photoelectrochemical assays for detection of methanol in alcoholic beverages.

Methanol is a poison which is frequently discovered in alcoholic beverages. Innovative methods to detect methanol in alcoholic beverages are being constantly developed. We report for the first time a new strategy for the detection of methanol using fluorescence spectroscopy and photoelectrochemical (PEC) analysis. The analytical system is based on the oxidation of cysteine (CSH) with hydrogen peroxide (H2O2) enzymatically generated by alcohol oxidase (AOx). H2O2 oxidizes capping agent CSH, modulating the growth of CSH-stabilized cadmium sulphide quantum dots (CdS QDs). Disposable screen-printed carbon electrodes (SPCEs) modified with a conductive osmium polymer (Os-PVP) complex were employed to quantify resulting CdS QDs. This polymer facilitates the "wiring" of in situ enzymatically generated CdS QDs, which photocatalyze oxidation of 1-thioglycerol (TG), generating photocurrent as the readout signal. Likewise, we proved that our systems did not suffer from interference by ethanol. The PEC assays showed better sensitivity than conventional methods, covering a wide range of potential applications for methanol quantification.

Photoelectrochemical detection of copper ions by modulating the growth of CdS quantum dots.

We discovered that copper ions (Cu2+) catalyze the oxidation of cysteine (CSH) by oxygen (O2) to modulate the growth of CSH-capped cadmium sulfide (CdS) nanoparticles (NPs). This new chemical process was applied to sensitive fluorogenic and photoelectrochemical (PEC) detection of Cu2+ ions in real samples of mineral and tap water using the photocatalytic activity of the resulting NPs. Disposable screen-printed electrodes (SPCEs) modified with electroactive polyvinylpyridine bearing osmium complex (Os-PVP) by cyclic voltammetry (CV) were employed for PEC analytical system. CdS NPs formed during the assay photocatalyze oxidation of 1-thioglycerol (TG) upon application of 0.3 V vs. Ag/AgCl to SPCEs. Os-PVP complex mediated the electron transfer between the electrode surface and CdS NPs. We proved that our assays did not suffer from interference from other ions accompanying Cu2+ and the sensitivity of our assays covers the European Union standard limit of Cu2+ ions in drinking water.