Correction: Virtual screening, identification and validation of small molecule GDP-mannose dehydrogenase inhibitors.

[This corrects the article DOI: 10.1039/D3CB00126A.].

Structural and mechanistic characterization of bifunctional heparan sulfate N-deacetylase-N-sulfotransferase 1.

Heparan sulfate (HS) polysaccharides are major constituents of the extracellular matrix, which are involved in myriad structural and signaling processes. Mature HS polysaccharides contain complex, non-templated patterns of sulfation and epimerization, which mediate interactions with diverse protein partners. Complex HS modifications form around initial clusters of glucosamine-N-sulfate (GlcNS) on nascent polysaccharide chains, but the mechanistic basis underpinning incorporation of GlcNS itself into HS remains unclear.

Virtual screening, identification and validation of small molecule GDP-mannose dehydrogenase inhibitors.

Upon undergoing mucoid conversion within the lungs of cystic fibrosis patients, the pathogenic bacterium synthesises copious quantities of the virulence factor and exopolysaccharide alginate. The enzyme guanosine diphosphate mannose dehydrogenase (GMD) catalyses the rate-limiting step and irreversible formation of the alginate sugar nucleotide building block, guanosine diphosphate mannuronic acid. Since there is no corresponding enzyme in humans, strategies that could prevent its mechanism of action could open a pathway for new and selective inhibitors to disrupt bacterial alginate production.

Harnessing a Biocatalyst to Bioremediate the Purification of Alkylglycosides.

As the world moves towards net-zero carbon emissions, the development of sustainable chemical manufacturing processes is essential. Within manufacturing, purification by distillation is often used, however this process is energy intensive and methods that could obviate or reduce its use are desirable. Developed herein is an alternative, oxidative biocatalytic approach that enables purification of alkyl monoglucosides (essential bio-based surfactant components).

Trace element, rare earth element and trace carbon compounds in Subglacial Lake Whillans, West Antarctica.

Whillans Subglacial Lake (SLW) lies beneath 801 m of ice in the lower portion of the Whillans Ice Stream (WIS) in West Antarctica and is part of an extensive and active subglacial drainage network. Here, the geochemical characterization of SLW rare earth elements (REE), trace elements (TE), free amino acids (FAA), and phenolic compounds (PC) measured in lakewater and sediment porewater are reported. The results show, on average, higher values of REEs in the lakewater than in the porewater, and clear changes in all REE concentrations and select redox sensitive trace element concentrations in porewaters at a depth of ~15 cm in the 38 cm lake sediment core.

Rural US residents recognize anxiety better than urbanites and suburbanites but hold similar stigma.

Purpose: Recognizing signs of psychological distress is a critical first step in assisting people who are struggling with poor mental health to access help. However, community-level factors that impact recognition and stigma are underexplored. The purpose of this study is to investigate the relationship between rurality, other community-level variables, and individual variables with regard to the recognition and stigma of anxiety.

Analysis of Heparin Samples by Attenuated Total Reflectance Fourier-Transform Infrared Spectroscopy in the Solid State.

Heparin is a polydisperse, heterogeneous polysaccharide of the glycosaminoglycan (GAG) class that has found widespread clinical use as a potent anticoagulant and is classified as an essential medicine by the World Health Organization. The importance of rigorous monitoring and quality control of pharmaceutical heparin was highlighted in 2008, when the existing regulatory procedures failed to identify a life-threatening adulteration of pharmaceutical heparin with oversulfated chondroitin sulfate (OSCS). The subsequent contamination crisis resulted in the exploration of alternative approaches for which the use of multidimensional nuclear magnetic resonance (NMR) spectroscopy techniques and multivariate analysis emerged as the gold standard.

High sensitivity (zeptomole) detection of BODIPY-labelled heparan sulfate (HS) disaccharides by ion-paired RP-HPLC and LIF detection enables analysis of HS from mosquito midguts.

The fine structure of heparan sulfate (HS), the glycosaminoglycan polysaccharide component of cell surface and extracellular matrix HS proteoglycans, coordinates the complex cell signalling processes that control homeostasis and drive development in multicellular animals. In addition, HS is involved in the infection of mammals by viruses, bacteria and parasites. The current detection limit for fluorescently labelled HS disaccharides (low femtomole; 10 mol), has effectively hampered investigations of HS composition in small, functionally-relevant populations of cells and tissues that may illuminate the structural requirements for infection and other biochemical processes.

A sulphated glycosaminoglycan extract from Placopecten magellanicus inhibits the Alzheimer's disease β-site amyloid precursor protein cleaving enzyme 1 (BACE-1).

The clinically important anticoagulant heparin, a member of the glycosaminoglycan family of carbohydrates that is extracted predominantly from porcine and bovine tissue sources, has previously been shown to inhibit the β-site amyloid precursor protein cleaving enzyme 1 (BACE-1), a key drug target in Alzheimer's Disease. In addition, heparin has been shown to exert favourable bioactivities through a number of pathophysiological pathways involved in the disease processes of Alzheimer's Disease including inflammation, oxidative stress, tau phosphorylation and amyloid peptide generation. Despite the multi-target potential of heparin as a therapeutic option for Alzheimer's disease, the repurposing of this medically important biomolecule has to-date been precluded by its high anticoagulant potential.

The role of social circle COVID-19 illness and vaccination experiences in COVID-19 vaccination decisions: an online survey of the United States population.

Background: Around the world, policymakers have clearly communicated that COVID-19 vaccination programs need to be accepted by a large proportion of the population to allow life return to normal. However, according to the Center for Disease Control, about 31% of the United States population had not completed the primary vaccination series as of November 2022.

Aims: The primary aim of this work is to identify the factors associated by American citizens with the decision to be vaccinated against COVID-19.

Iron Minerals Influence the Assembly of Microbial Communities in a Basaltic Glacial Catchment.

The influence of mineralogy on the assembly of microbial communities in glacial environments has been difficult to assess due to complications in isolating mineralogy from other variables. Here we assess the abundance and composition of microbial communities that colonized defined minerals incubated for 12 months in two meltwater streams (N and S) emanating from Kaldalónsjökull (Kal), a basalt-hosted glacier in Iceland. The two streams shared similar meltwater geochemistry as well as bedrock and proglacial sediment elemental compositions.

Evidence for Multiple Binding Modes in the Initial Contact Between SARS-CoV-2 Spike S1 Protein and Cell Surface Glycans.

Infection of host cells by SARS-CoV-2 begins with recognition by the virus S (spike) protein of cell surface heparan sulfate (HS), tethering the virus to the extracellular matrix environment, and causing the subunit S1-RBD to undergo a conformational change into the 'open' conformation. These two events promote the binding of S1-RBD to the angiotensin converting enzyme 2 (ACE2) receptor, a preliminary step toward viral-cell membrane fusion. Combining ligand-based NMR spectroscopy with molecular dynamics, oligosaccharide analogues were used to explore the interactions between S1-RBD of SARS CoV-2 and HS, revealing several low-specificity binding modes and previously unidentified potential sites for the binding of extended HS polysaccharide chains.

An Effective Mental Health Literacy Program for Farm Financial Service Providers.

Objectives: Mental health literacy programs related to agriculture can help enhance skills among agricultural community members and service providers to assist farmers and producers who are experiencing distress. The aim of the current article is to describe an agricultural mental health literacy education-based intervention program offered to USDA Farm Service Agency farm financial service providers. The program was implemented as a self-paced, online training through USDA's AgLearn platform to N = 500 FSA staff.

The Hyperlipidaemic Drug Fenofibrate Significantly Reduces Infection by SARS-CoV-2 in Cell Culture Models.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic has caused a significant number of fatalities and worldwide disruption. To identify drugs to repurpose to treat SARS-CoV-2 infections, we established a screen to measure the dimerization of angiotensin-converting enzyme 2 (ACE2), the primary receptor for the virus. This screen identified fenofibric acid, the active metabolite of fenofibrate.

Evidence of a putative glycosaminoglycan binding site on the glycosylated SARS-CoV-2 spike protein N-terminal domain.

SARS-CoV-2 has rapidly spread throughout the world's population since its initial discovery in 2019. The virus infects cells via a glycosylated spike protein located on its surface. The protein primarily binds to the angiotensin-converting enzyme-2 (ACE2) receptor, using glycosaminoglycans (GAGs) as co-receptors.

Glycosaminoglycans from Inhibit the Alzheimer's Disease β Secretase, BACE1.

Only palliative therapeutic options exist for the treatment of Alzheimer's Disease; no new successful drug candidates have been developed in over 15 years. The widely used clinical anticoagulant heparin has been reported to exert beneficial effects through multiple pathophysiological pathways involved in the aetiology of Alzheimer's Disease, for example, amyloid peptide production and clearance, tau phosphorylation, inflammation and oxidative stress. Despite the therapeutic potential of heparin as a multi-target drug for Alzheimer's disease, the repurposing of pharmaceutical heparin is proscribed owing to the potent anticoagulant activity of this drug.

Lithogenic hydrogen supports microbial primary production in subglacial and proglacial environments.

Life in environments devoid of photosynthesis, such as on early Earth or in contemporary dark subsurface ecosystems, is supported by chemical energy. How, when, and where chemical nutrients released from the geosphere fuel chemosynthetic biospheres is fundamental to understanding the distribution and diversity of life, both today and in the geologic past. Hydrogen (H) is a potent reductant that can be generated when water interacts with reactive components of mineral surfaces such as silicate radicals and ferrous iron.

Heparin Inhibits Cellular Invasion by SARS-CoV-2: Structural Dependence of the Interaction of the Spike S1 Receptor-Binding Domain with Heparin.

The dependence of development and homeostasis in animals on the interaction of hundreds of extracellular regulatory proteins with the peri- and extracellular glycosaminoglycan heparan sulfate (HS) is exploited by many microbial pathogens as a means of adherence and invasion. Heparin, a widely used anticoagulant drug, is structurally similar to HS and is a common experimental proxy. Exogenous heparin prevents infection by a range of viruses, including S-associated coronavirus isolate HSR1.

Development of a nano-luciferase based assay to measure the binding of SARS-CoV-2 spike receptor binding domain to ACE-2.

To identify drugs that could potentially be used to treat infection with SARS-CoV-2, a high throughput 384-well assay was developed to measure the binding of the receptor binding domain (RBD) of the viral S1 protein to its main receptor, angiotensin converting enzyme 2 (ACE2). The RBD was fused to both a HiBIT tag and an IL6 secretion signal to enable facile collection from the cell culture media. The addition of culture media containing this protein, termed HiBIT-RBD, to cells expressing ACE2 led to binding that was specific to ACE2 and both time and concentration dependant, Binding could be inhibited by both RBD expressed in E.

Enhanced trace element mobilization by Earth's ice sheets.

Trace elements sustain biological productivity, yet the significance of trace element mobilization and export in subglacial runoff from ice sheets is poorly constrained at present. Here, we present size-fractionated (0.02, 0.

Molecular Changes in Dengue Envelope Protein Domain III upon Interaction with Glycosaminoglycans.

Dengue fever is a rapidly emerging vector-borne viral disease with a growing global burden of approximately 390 million new infections per annum. The Dengue virus (DENV) is a flavivirus spread by female mosquitos of the genus, but the mechanism of viral endocytosis is poorly understood at a molecular level, preventing the development of effective transmission blocking vaccines (TBVs). Recently, glycosaminoglycans (GAGs) have been identified as playing a role during initial viral attachment through interaction with the third domain of the viral envelope protein (EDIII).