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Mesolithic Scandinavian foraging patterns and hunting grounds targeted through laser ablation derived 87Sr/86Sr ratios at the Early-Mid Holocene site of Huseby Klev on the west coast of Sweden

Mobility is one of the most fundamental aspects of a foraging society. Since prehistoric mobility is often difficult to identify in the archaeological record, our understanding is largely based on comparison with ethnographic communities. In recent years the application of 87Sr/86Sr isotope analysis has, however, greatly broadened our knowledge of mobility in the past. Despite this, few studies ha

Cannabinoid non-cannabidiol site modulation of TRPV2 structure and function

TRPV2 is a ligand-operated temperature sensor with poorly defined pharmacology. Here, we combine calcium imaging and patch-clamp electrophysiology with cryo-electron microscopy (cryo-EM) to explore how TRPV2 activity is modulated by the phytocannabinoid Δ9-tetrahydrocannabiorcol (C16) and by probenecid. C16 and probenecid act in concert to stimulate TRPV2 responses including histamine release from

Influence of nuclides and chelators on imaging using affibody molecules : comparative evaluation of recombinant affibody molecules site-specifically labeled with ⁶⁸Ga and ¹¹¹In via maleimido derivatives of DOTA and NODAGA

Accurate detection of cancer-associated molecular abnormalities in tumors could make cancer treatment more personalized. Affibody molecules enable high contrast imaging of tumor-associated protein expression shortly after injection. The use of the generator-produced positron-emitting radionuclide (68)Ga should increase sensitivity of HER2 imaging. The chemical nature of radionuclides and chelators

Effects of conventionally treated and ozonated wastewater on the damselfly larva oxylipidome in response to on-site exposure

Pharmaceutical residues discharged through insufficiently treated or untreated wastewater enter aquatic environments, where they may adversely impact organisms such as aquatic invertebrates. Ozonation, an advanced wastewater treatment technique, has been successfully implemented to enhance the removal of a broad range of pharmaceuticals, however diverse byproducts and transformation products that

The ethics and politics of world heritage : local application at the site of Laponia

This article explores the ethics of world heritage (WH) through a cosmopolitan lens. It proposes that cosmopolitanism provides fertile ground for the study of WH, in particular if combined with sensitivity to distinct indigenous ethical and political claims. Underpinning my article is the question of whether the politics of WH, despite its peaceful and universalist intensions, obscures local dispu

Conformational Response of 30S-bound IF3 to A-Site Binders Streptomycin and Kanamycin

Aminoglycoside antibiotics are widely used to treat infectious diseases. Among them, streptomycin and kanamycin (and derivatives) are of importance to battle multidrug-resistant (MDR) Mycobacterium tuberculosis. Both drugs bind the small ribosomal subunit (30S) and inhibit protein synthesis. Genetic, structural, and biochemical studies indicate that local and long-range conformational rearrangemen

Site-Specific Introduction of Negative Charges on the Protein Surface for Improving Global Functions of Recombinant Fetal Hemoglobin

Due to its compatible oxygen-transporting abilities, hemoglobin (Hb) is a protein of interest in the development of artificial oxygen therapeutics. Despite continuous formulation attempts, extracellular Hb solution often exhibits undesirable reactions when applied in vivo. Therefore, protein engineering is frequently used to examine alternative ways of controlling the unwanted reactions linked to

Dose-response analysis of protracted absorbed organ dose and site-specific cancer incidence in Sweden after the Chernobyl nuclear power plant accident

Background: Adult males in Sweden exhibit an increased risk of cancer associated with an increased absorbed dose to the colon from the Chernobyl accident. Methods: A closed cohort, with information on hunter status, included all individuals living in northern Sweden in 1986. Complete annual information on exposure to 137Cs at the dwelling coordinate was available for a total of 2,104,101 individua

Sulfonamide-derivatized galactosides selectively target an unexplored binding site in the galectin-9N-terminal domain

Four directional and positional variants of sulfonamide-derivatized galactopyranosides were synthesized and evaluated against human galectin-1, -3, -4C (C-terminal), -7, -8N (N-terminal), -8C (C-terminal), -9N (N-terminal), and -9C (C-terminal), which revealed that one of the sulfonamide positions and directionalities (methyl 3-{4-[2-(phenylsulfonylamino)-phenyl]-triazolyl}-3-deoxy-α-D-galactopyra

Modeling the Role of a Flexible Loop and Active Site Side Chains in Hydride Transfer Catalyzed by Glycerol-3-phosphate Dehydrogenase

Glycerol-3-phosphate dehydrogenase is a biomedically important enzyme that plays a crucial role in lipid biosynthesis. It is activated by a ligand-gated conformational change that is necessary for the enzyme to reach a catalytically competent conformation capable of efficient transition-state stabilization. While the human form (hlGPDH) has been the subject of extensive structural and biochemical

Short and simple sequences favored the emergence of N-helix phospho-ligand binding sites in the first enzymes

The ubiquity of phospho-ligands suggests that phosphate binding emerged at the earliest stage of protein evolution. To evaluate this hypothesis and unravel its details, we identified all phosphate-binding protein lineages in the Evolutionary Classification of Protein Domains database. We found at least 250 independent evolutionary lineages that bind small molecule cofactors and metabolites with ph

GTP Hydrolysis Without an Active Site Base : A Unifying Mechanism for Ras and Related GTPases

GTP hydrolysis is a biologically crucial reaction, being involved in regulating almost all cellular processes. As a result, the enzymes that catalyze this reaction are among the most important drug targets. Despite their vital importance and decades of substantial research effort, the fundamental mechanism of enzyme-catalyzed GTP hydrolysis by GTPases remains highly controversial. Specifically, ho

Catalytic stimulation by restrained active-site floppiness--the case of high density lipoprotein-bound serum paraoxonase-1

Despite the abundance of membrane-associated enzymes, the mechanism by which membrane binding stabilizes these enzymes and stimulates their catalysis remains largely unknown. Serum paraoxonase-1 (PON1) is a lipophilic lactonase whose stability and enzymatic activity are dramatically stimulated when associated with high-density lipoprotein (HDL) particles. Our mutational and structural analyses, co

Contaminant, Commodity and Fuel: A Multi‐sited Study of Waste's roles in Urban Transformations from Italy to Austria

This article traces the flow of municipal solid waste from southern Italy through a waste‐to‐energy facility and district heating system in Austria, examining the roles that waste's transformation from contaminant to commodity to fuel plays in interconnected, distributed, and contested urbanization processes. It contends that, while metabolic circulation hides socioecological costs in one place to

Translational stalling at polyproline stretches is modulated by the sequence context upstream of the stall site

The polymerization of amino acids into proteins occurs on ribosomes, with the rate influenced by the amino acids being polymerized. The imino acid proline is a poor donor and acceptor for peptide-bond formation, such that translational stalling occurs when three or more consecutive prolines (PPP) are encountered by the ribosome. In bacteria, stalling at PPP motifs is rescued by the elongation fact