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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

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

Protonation State of Active-Site Histidines, Reaction Mechanism and Stereoselectivity in β-Alanine Synthase : A Computational Study

β-Alanine synthase (βAS), which is a dizinc metalloenzyme, catalyzes the irreversible hydrolysis of N-carbamyl-β-alanine (NCβA) to β-alanine. This enzyme has potential applications for β-amino acid production. Understanding the reaction mechanism and selectivity of βAS at atomic details can help design and engineer the enzyme for cascade biocatalysis. Here, the protonation states of two conserved

PAH exposure and associated health risks can be high at a fire site both during fire and long after the fire is extinguished

The International Agency for Research on Cancer has recently classified occupational exposure as a firefighter as carcinogenic (group 1A). Even though the occupation of firefighter is associated with high exposure to pollutants, it is challenging to carry out exposure studies to assess health risks due to the extreme conditions associated with firefighting. Routine monitoring of occupational expos

Aggrecan accumulates at sites of increased pulmonary arterial pressure in idiopathic pulmonary arterial hypertension

Expansion of extracellular matrix occurs in all stages of pulmonary angiopathy associated with pulmonary arterial hypertension (PAH). In systemic arteries, dysregulation and accumulation of the large chondroitin-sulfate proteoglycan aggrecan is associated with swelling and disruption of vessel wall homeostasis. Whether aggrecan is present in pulmonary arteries, and its potential roles in PAH, has

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

Novel Function of CtXyn5A from Acetivibrio thermocellus: Dual Arabinoxylanase and Feruloyl Esterase Activity Occur in the Same Active Site

Uncharacterized side activities of enzymes can have significant negative effects on reaction products and yields. Hence, their identification and characterization is crucial for the development of successful reaction systems. Here, we report the presence of feruloyl esterase activity in CtXyn5A from Acetivibrio thermocellus besides its well-known arabinoxylanase activity for the first time. Both r

Design and implementation of a web interface for Axis global testing Live Sites

Designing and developing a software product is a difficult process. The product must be usable and solve the correct problem. At the same time, the underlying code must be well written. Many projects fail to deliver or exceed their budget. This thesis explores a practical approach to software design and development that tries to adhere to both user centered design and agile development. The proces

The link between secondary organic aerosol and monoterpenes at a boreal forest site

Secondary organic aerosol (SOA) plays a significant role in climate change by altering the global atmospheric radiation budget. Biogenic volatile organic compounds (BVOCs) are major sources for the formation of SOA. Their relationship is critical to understand the continental biosphere-aerosol-cloud-climate (COBACC) feedback mechanism but receives less attention in previous studies. In this study,

Evaluating a new hydraulic implementation in LPJ-GUESS for three sites in north Europe

Drought is projected to increase in frequency and intensity and impacts trees with increased water stress and increased mortality rate. Water stresses can cause hydraulic failure-related mortality or carbon starvation due to tree species having different strategies to deal with water stresses. LPJ-GUESS-HYD (Hydraulic implementation of a new plant hydraulics scheme in LPJ-GUESS) was developed to i

EMBODIED ENGAGEMENTS WITH THE ECOLOGICAL CRISIS: Investigating Performative Spaces as Sites of Resistance to Capitalist Societal Norms

Although the accounts confirming that we are in the midst of an ecological crisis are undeniable, the transformative action necessary to address climate change remains elusive. Capitalist norms of economic growth, self-interest and denialism obstructs paths towards sustainability. This research illustrates how embodied engagements with the ecological crisis through artistic practices can foster mo