The phosphylated butyrylcholinesterase-derived tetrapeptide GlyGluSerAla proves exposure to organophosphorus agents with enantioselectivity.

We herein present for the first time the phosphylated (*) tetrapeptide (TP)-adduct GlyGluSerAla generated from butyrylcholinesterase (BChE) with proteinase K excellently suited for the verification of exposure to toxic organophosphorus nerve agents (OPNA). Verification requires bioanalytical methods mandatory for toxicological and legal reasons. OPNA react with BChE by phosphonylation of the active site serine residue (Ser) forming one of the major target protein adducts for verification.

An ancient river landscape preserved beneath the East Antarctic Ice Sheet.

The East Antarctic Ice Sheet (EAIS) has its origins ca. 34 million years ago. Since then, the impact of climate change and past fluctuations in the EAIS margin has been reflected in periods of extensive vs.

[Health of people with selected citizenships in Germany: prevalence of non-communicable diseases and associated social as well as migration-related factors].

Background: Health chances and risks of people with a history of migration vary according to a wide range of factors. This paper aims to describe the health of people with selected citizenships on the basis of four non-communicable diseases (chronic disease or long-term health problem in general, coronary heart disease, diabetes mellitus, depression) and to identify associated social and migration-related factors.

Methods: Analyses are based on data from the multilingual and multimodal interview survey "German Health Update: Fokus" (GEDA Fokus), which was conducted among 18- to 79-year-olds with Croatian, Italian, Polish, Syrian, or Turkish citizenship living in Germany (November 2021 to May 2022).

Highly stable peptide adducts from hard keratins as biomarkers to verify local sulfur mustard exposure of hair by high-resolution mass spectrometry.

In the recent past, the blister agent sulfur mustard (SM) deployed by the terroristic group Islamic State has caused a huge number of civilian and military casualties in armed conflicts in the Middle East. The vaporized or aerolized agent might be inhaled and have direct contact to skin and hair. Reaction products of SM with plasma proteins (adducts) represent well-established systemic targets for the bioanalytical verification of exposure.

Nontargeted High-Resolution Mass Spectrometric Workflow for the Detection of Butyrylcholinesterase-Derived Adducts with Organophosphorus Toxicants and Structural Characterization of Their Phosphyl Moiety after In-Source Fragmentation.

Organophosphorus (OP) nerve agents were used for chemical warfare, assassination, and attempted murder of individuals. Therefore, forensic methods are required to identify known and unknown incorporated OP poisons. Serum is tested for the presence of covalent reaction products (adducts) of the toxicant with, e.

A large West Antarctic Ice Sheet explains early Neogene sea-level amplitude.

Early to Middle Miocene sea-level oscillations of approximately 40-60 m estimated from far-field records are interpreted to reflect the loss of virtually all East Antarctic ice during peak warmth. This contrasts with ice-sheet model experiments suggesting most terrestrial ice in East Antarctica was retained even during the warmest intervals of the Middle Miocene. Data and model outputs can be reconciled if a large West Antarctic Ice Sheet (WAIS) existed and expanded across most of the outer continental shelf during the Early Miocene, accounting for maximum ice-sheet volumes.

Alkylation of rabbit muscle creatine kinase surface methionine residues inhibits enzyme activity in vitro.

Creatine kinase (CK) catalyzes the formation of phosphocreatine from adenosine triphosphate (ATP) and creatine. The highly reactive free cysteine residue in the active site of the enzyme (Cys) is considered essential for the enzymatic activity. In previous studies we demonstrated that Cys is targeted by the alkylating chemical warfare agent sulfur mustard (SM) yielding a thioether with a hydroxyethylthioethyl (HETE)-moiety.

Alkylated albumin-derived dipeptide C(-HETE)P derivatized by propionic anhydride as a biomarker for the verification of poisoning with sulfur mustard.

Sulfur mustard (SM) is a banned chemical warfare agent recently used in the Syrian Arab Republic conflict causing erythema and blisters characterized by complicated and delayed wound healing. For medical and legal reasons, the proof of exposure to SM is of high toxicological and forensic relevance. SM reacts with endogenous human serum albumin (HSA adducts) alkylating the thiol group of the cysteine residue C, thus causing the addition of the hydroxyethylthioethyl (HETE) moiety.

Novel irreversible covalent BTK inhibitors discovered using DNA-encoded chemistry.

Libraries of DNA-Encoded small molecules created using combinatorial chemistry and synthetic oligonucleotides are being applied to drug discovery projects across the pharmaceutical industry. The majority of reported projects describe the discovery of reversible, i.e.

Alkylated epidermal creatine kinase as a biomarker for sulfur mustard exposure: comparison to adducts of albumin and DNA in an in vivo rat study.

Sulfur mustard (SM) is a chemical warfare agent which use is banned under international law and that has been used recently in Northern Iraq and Syria by the so-called Islamic State. SM induces the alkylation of endogenous proteins like albumin and hemoglobin thus forming covalent adducts that are targeted by bioanalytical methods for the verification of systemic poisoning. We herein report a novel biomarker, namely creatine kinase (CK) B-type, suitable as a local biomarker for SM exposure on the skin.

Dynamic flows create potentially habitable conditions in Antarctic subglacial lakes.

Trapped beneath the Antarctic ice sheet lie over 400 subglacial lakes, which are considered to be extreme, isolated, yet viable habitats for microbial life. The physical conditions within subglacial lakes are critical to evaluating how and where life may best exist. Here, we propose that Earth's geothermal flux provides efficient stirring of Antarctic subglacial lake water.

Integrating endocrine-related health effects into comparative human toxicity characterization.

Endocrine-disrupting chemicals have the ability to interfere with and alter functions of the hormone system, leading to adverse effects on reproduction, growth and development. Despite growing concerns over their now ubiquitous presence in the environment, endocrine-related human health effects remain largely outside of comparative human toxicity characterization frameworks as applied for example in life cycle impact assessments. In this paper, we propose a new methodological framework to consistently integrate endocrine-related health effects into comparative human toxicity characterization.

Integral correlation for uneven and differently sampled data, and its application to the Law Dome Antarctic climate record.

We present a new simple and efficient method for correlation of unevenly and differently sampled data. This new method overcomes problems with other methods for correlation with non-uniform sampling and is an easy modification to existing correlation based codes. To demonstrate the usefulness of this new method to real-world examples, we apply the method with good success to two glaciological examples to map the ages from a well-dated ice core to a nearby core, and by tracing isochronous layers within the ice sheet measured from ice-penetrating radar between the two ice core sites.

HOMO-HOMO Electron Transfer: An Elegant Strategy for p-Type Doping of Polymer Semiconductors toward Thermoelectric Applications.

Unlike the conventional p-doping of organic semiconductors (OSCs) using acceptors, here, an efficient doping concept for diketopyrrolopyrrole-based polymer PDPP[T] -EDOT (OSC-1) is presented using an oxidized p-type semiconductor, Spiro-OMeTAD(TFSI) (OSC-2), exploiting electron transfer from HOMO to HOMO . A shift of work function toward the HOMO upon doping is confirmed by ultraviolet photoelectron spectroscopy (UPS). Detailed X-ray photoelectron spectroscopy (XPS) and UV-vis-NIR absorption studies confirm HOMO to HOMO electron transfer.

Adduct of the blistering warfare agent sesquimustard with human serum albumin and its mass spectrometric identification for biomedical verification of exposure.

Apart from the well-known sulfur mustard (SM), additional sulfur-containing blistering chemical warfare agents exist. Sesquimustard (Q) is one of them and five times more blistering than SM. It is a common impurity in mustard mixtures and regularly found in old munitions but can also be used in pure form.

Identification of creatine kinase and alpha-1 antitrypsin as protein targets of alkylation by sulfur mustard.

Sulfur mustard (SM) is a toxic chemical warfare agent deployed in several conflicts within the last 100 years and still represents a threat in terroristic attacks and warfare. SM research focuses on understanding the pathophysiology of SM and identifying novel biomarkers of exposure. SM is known to alkylate nucleophilic moieties of endogenous proteins, for example, free thiol groups of cysteine residues.

An Amphipathic Alpha-Helix Guides Maturation of the Ribosomally-Synthesized Lipolanthines.

The recently discovered strongly anti-Gram-positive lipolanthines represent a new group of lipidated, ribosomally synthesized and post-translationally modified peptides (RiPPs). They are bicyclic octapeptides with a central quaternary carbon atom (avionin), which is installed through the cooperative action of the class-III lanthipeptide synthetase MicKC and the cysteine decarboxylase MicD. Genome mining efforts indicate a widespread distribution and unprecedented biosynthetic diversity of lipolanthine gene clusters, combining elements of RiPPs, polyketide and non-ribosomal peptide biosynthesis.

Digital rock physics and laboratory considerations on a high-porosity volcanic rock.

Digital rock physics combines microtomographic imaging with advanced numerical simulations of effective material properties. It is used to complement laboratory investigations with the aim to gain a deeper understanding of relevant physical processes related to transport and effective mechanical properties. We apply digital rock physics to reticulite, a natural mineral with a strong analogy to synthetic open-cell foams.

A Convergent Total Synthesis of the Death Cap Toxin α-Amanitin.

The toxic bicyclic octapeptide α-amanitin is mostly found in different species of the mushroom genus Amanita, with the death cap (Amanita phalloides) as one of the most prominent members. Due to its high selective inhibition of RNA polymerase II, which is directly linked to its high toxicity, particularly to hepatocytes, α-amanitin received an increased attention as a toxin-component of antibody-drug conjugates (ADC) in cancer research. Furthermore, the isolation of α-amanitin from mushrooms as the sole source severely restricts compound supply as well as further investigations, as structure-activity relationship (SAR) studies.

Multidecadal observations of the Antarctic ice sheet from restored analog radar records.

Airborne radar sounding can measure conditions within and beneath polar ice sheets. In Antarctica, most digital radar-sounding data have been collected in the last 2 decades, limiting our ability to understand processes that govern longer-term ice-sheet behavior. Here, we demonstrate how analog radar data collected over 40 y ago in Antarctica can be combined with modern records to quantify multidecadal changes.

Skin sensitizing effects of sulfur mustard and other alkylating agents in accordance to OECD guidelines.

Vesicants cause a multitude of cutaneous reactions like erythema, blisters and ulcerations. After exposure to sulfur mustard (SM) and related compounds, patients present dermal symptoms typically known for chemicals categorized as skin sensitizer (e.g.

Forensic evidence of sulfur mustard exposure in real cases of human poisoning by detection of diverse albumin-derived protein adducts.

We present the forensic analyses of plasma samples of human victims exposed to sulfur mustard (SM) in a crisis region in the Middle East in 2015. A few hours after exposure, poisoned persons showed typical signs and symptoms of percutaneous SM exposure including erythema and later on blisters and hardly healing skin wounds. Blood samples were collected 15 days after poisoning to be analyzed for the presence of long-lived protein-adduct biomarkers to verify SM poisoning.