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Characterizing Performance of Freshwater Wetland Methane Models Across Time Scales at FLUXNET-CH4 Sites Using Wavelet Analyses
Process-based land surface models are important tools for estimating global wetland methane (CH4) emissions and projecting their behavior across space and time. So far there are no performance assessments of model responses to drivers at multiple time scales. In this study, we apply wavelet analysis to identify the dominant time scales contributing to model uncertainty in the frequency domain. We
Sites of Collective Resistance
This work is concerned with the production of social space through cultural and performance practices; it proposes the collective production of space as a mode of resistance and examines performance manifestations, occupations and constructions within the contemporary neoliberal landscape. The thesis seeks to develop a mode of critical engagement with the spatial – its constraints and potentialiti
ISLAND, A SITE SPECIFIC AND HUMAN SPECIFIC PERFORMANCE ABOUT WHAT IT MEANS TO BELONG
Large-Scale Crystallographic Fragment Screening Expedites Compound Optimization and Identifies Putative Protein-Protein Interaction Sites
The identification of starting points for compound development is one of the key steps in early-stage drug discovery. Information-rich techniques such as crystallographic fragment screening can potentially increase the efficiency of this step by providing the structural information of the binding mode of the ligands in addition to the mere binding information. Here, we present the crystallographic
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
Shuffling Active Site Substate Populations Affects Catalytic Activity : The Case of Glucose Oxidase
Glucose oxidase has wide applications in the pharmaceutical, chemical, and food industries. Many recent studies have enhanced key properties of this enzyme using directed evolution, yet without being able to reveal why these mutations are actually beneficial. This work presents a synergistic combination of experimental and computational methods, indicating how mutations, even when distant from the
Investigating the differences in calculating global mean surface CO2 abundance: the impact of analysis methodologies and site selection
The World Meteorological Organization (WMO) Global Atmosphere Watch (GAW) coordinates high-quality atmospheric greenhouse gas observations globally and provides these observations through the WMO World Data Centre for Greenhouse Gases (WDCGG) supported by Japan Meteorological Agency. The WDCGG and the National Oceanic and Atmospheric Administration (NOAA) analyse these measurements using different
Similar Active Sites and Mechanisms Do Not Lead to Cross-Promiscuity in Organophosphate Hydrolysis : Implications for Biotherapeutic Engineering
Organophosphate hydrolases are proficient catalysts of the breakdown of neurotoxic organophosphates and have great potential as both biotherapeutics for treating acute organophosphate toxicity and as bioremediation agents. However, proficient organophosphatases such as serum paraoxonase 1 (PON1) and the organophosphate-hydrolyzing lactonase SsoPox are unable to hydrolyze bulkyorganophosphates with
De novo active sites for resurrected Precambrian enzymes
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
Changes in waterbird occurrence and abundance at their northern range boundaries in response to climate warming : importance of site area and protection status
Climate warming is driving changes in species distribution, but habitat characteristics can interact with warming temperatures to affect populations in unexpected ways. We investigated wintering waterbird responses to climate warming depending on habitat characteristics, with a focus on the northern boundary of their non-breeding distributions where winter climatic conditions are more extreme. At
Release of halide ions from the buried active site of the haloalkane dehalogenase LinB revealed by stopped-flow fluorescence analysis and free energy calculations
OSBP-mediated PI(4)P-cholesterol exchange at endoplasmic reticulum-secretory granule contact sites controls insulin secretion
Evidence of Site-Specific and Male-Biased Germline Mutation Rate in a Wild Songbird
Germline mutations are the ultimate source of genetic variation and the raw material for organismal evolution. Despite their significance, the frequency and genomic locations of mutations, as well as potential sex bias, are yet to be widely investigated in most species. To address these gaps, we conducted whole-genome sequencing of 12 great reed warblers (Acrocephalus arundinaceus) in a pedigree s
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
