A Bioorthogonal Precision Tool for Human -Acetylglucosaminyltransferase V.

Correct elaboration of N-linked glycans in the secretory pathway of human cells is essential in physiology. Early N-glycan biosynthesis follows an assembly line principle before undergoing crucial elaboration points that feature the sequential incorporation of the sugar -acetylglucosamine (GlcNAc). The activity of GlcNAc transferase V (MGAT5) primes the biosynthesis of an N-glycan antenna that is heavily upregulated in cancer.

Expanding the repertoire of GalNAc analogues for cell-specific bioorthogonal tagging of glycoproteins.

Glycosylation is a ubiquitous modification of proteins, necessitating approaches for its visualization and characterization. Bioorthogonally tagged monosaccharides have been instrumental to this end, offering a chemical view into the cell biology of glycans. Understanding the use of such monosaccharides by cellular biosynthetic pathways has expanded their applicability in cell biology, for instance through the strategy named Bio-Orthogonal Cell-specific TAgging of Glycoproteins (BOCTAG).

Voices: Challenges and opportunities for bioorthogonal chemistry.

Bioorthogonal chemistry was deservedly recognized with the 2022 Nobel Prize in Chemistry, having transformed the way chemists and biologists interrogate biological systems in the past twenty years. This Voices piece asks researchers from a range of backgrounds: what are some major challenges and opportunities facing the field in coming years?

Projection of extreme heat- and cold-related mortality in Sweden based on the spatial synoptic classification.

Background: Climate change is projected to result in increased heat events and decreased cold events. This will substantially impact human health, particularly when compounded with demographic change. This study employed the Spatial Synoptic Classification (SSC) to categorize daily weather into one of seven types.

Molecular mechanism of decision-making in glycosaminoglycan biosynthesis.

Two major glycosaminoglycan types, heparan sulfate (HS) and chondroitin sulfate (CS), control many aspects of development and physiology in a type-specific manner. HS and CS are attached to core proteins via a common linker tetrasaccharide, but differ in their polymer backbones. How core proteins are specifically modified with HS or CS has been an enduring mystery.

Socioeconomic and geographical inequalities in health care coverage in Mozambique: a repeated cross-sectional study of the 2015 and 2018 national surveys.

Background: Over the past years, Mozambique has implemented several initiatives to ensure equitable coverage to health care services. While there have been some achievements in health care coverage at the population level, the effects of these initiatives on social inequalities have not been analysed.

Objective: The present study aimed to assess changes in socioeconomic and geographical inequalities (education, wealth, region, place of residence) in health care coverage between 2015 and 2018 in Mozambique.

O-Linked Sialoglycans Modulate the Proteolysis of SARS-CoV-2 Spike and Likely Contribute to the Mutational Trajectory in Variants of Concern.

The emergence of a polybasic cleavage motif for the protease furin in SARS-CoV-2 spike has been established as a major factor for human viral transmission. The region N-terminal to that motif is extensively mutated in variants of concern (VOCs). Besides furin, spikes from these variants appear to rely on other proteases for maturation, including TMPRSS2.

Upregulation of GALNT7 in prostate cancer modifies O-glycosylation and promotes tumour growth.

Prostate cancer is the most common cancer in men and it is estimated that over 350,000 men worldwide die of prostate cancer every year. There remains an unmet clinical need to improve how clinically significant prostate cancer is diagnosed and develop new treatments for advanced disease. Aberrant glycosylation is a hallmark of cancer implicated in tumour growth, metastasis, and immune evasion.

Butyrate Differentiates Permissiveness to Clostridioides difficile Infection and Influences Growth of Diverse C. difficile Isolates.

A disrupted "dysbiotic" gut microbiome engenders susceptibility to the diarrheal pathogen Clostridioides difficile by impacting the metabolic milieu of the gut. Diet, in particular the microbiota-accessible carbohydrates (MACs) found in dietary fiber, is one of the most powerful ways to affect the composition and metabolic output of the gut microbiome. As such, diet is a powerful tool for understanding the biology of C.

Bump-and-hole engineering of human polypeptide N-acetylgalactosamine transferases to dissect their protein substrates and glycosylation sites in cells.

Despite the known disease relevance of glycans, the biological function and substrate specificities of individual glycosyltransferases are often ill-defined. Here, we describe a protocol to develop chemical, bioorthogonal reporters for the activity of the GalNAc-T family of glycosyltransferases using a tactic termed bump-and-hole engineering. This allows identification of the protein substrates and glycosylation sites of single GalNAc-Ts.

Cell-specific bioorthogonal tagging of glycoproteins.

Altered glycoprotein expression is an undisputed corollary of cancer development. Understanding these alterations is paramount but hampered by limitations underlying cellular model systems. For instance, the intricate interactions between tumour and host cannot be adequately recapitulated in monoculture of tumour-derived cell lines.

MatriGrid Based Biological Morphologies: Tools for 3D Cell Culturing.

Recent trends in 3D cell culturing has placed organotypic tissue models at another level. Now, not only is the microenvironment at the cynosure of this research, but rather, microscopic geometrical parameters are also decisive for mimicking a tissue model. Over the years, technologies such as micromachining, 3D printing, and hydrogels are making the foundation of this field.

Wealth inequalities in reproductive and child health preventive care in Mozambique: a decomposition analysis.

Background: Assessing the gap between rich and poor is important to monitor inequalities in health. Identifying the contribution to that gap can help policymakers to develop interventions towards decreasing that difference.

Objective: To quantify the wealth inequalities in health preventive measures (bed net use, vaccination, and contraceptive use) to determine the demographic and socioeconomic contribution factors to that inequality using a decomposition analysis.

4-Deoxy-4-fluoro-GalNAz (4FGalNAz) Is a Metabolic Chemical Reporter of O-GlcNAc Modifications, Highlighting the Notable Substrate Flexibility of O-GlcNAc Transferase.

Bio-orthogonal chemistries have revolutionized many fields. For example, metabolic chemical reporters (MCRs) of glycosylation are analogues of monosaccharides that contain a bio-orthogonal functionality, such as azides or alkynes. MCRs are metabolically incorporated into glycoproteins by living systems, and bio-orthogonal reactions can be subsequently employed to install visualization and enrichment tags.

Ambient temperature and stillbirth risks in northern Sweden, 1880-1950.

Background: Climate vulnerability of the unborn can contribute to adverse birth outcomes, in particular, but it is still not well understood. We investigated the association between ambient temperature and stillbirth risk among a historical population in northern Sweden (1880-1950).

Methods: We used digitized parish records and daily temperature data from the study region covering coastal and inland communities some 600 km north of Stockholm, Sweden.

Benefits of Chemical Sugar Modifications Introduced by Click Chemistry for Glycoproteomic Analyses.

Mucin-type O-glycosylation is among the most complex post-translational modifications. Despite mediating many physiological processes, O-glycosylation remains understudied compared to other modifications, simply because the right analytical tools are lacking. In particular, analysis of intact O-glycopeptides by mass spectrometry is challenging for several reasons; O-glycosylation lacks a consensus motif, glycopeptides have low charge density which impairs ETD fragmentation, and the glycan structures modifying the peptides are unpredictable.

Optimization of Metabolic Oligosaccharide Engineering with AcGalNAlk and AcGlcNAlk by an Engineered Pyrophosphorylase.

Metabolic oligosaccharide engineering (MOE) has fundamentally contributed to our understanding of protein glycosylation. Efficient MOE reagents are activated into nucleotide-sugars by cellular biosynthetic machineries, introduced into glycoproteins and traceable by bioorthogonal chemistry. Despite their widespread use, the metabolic fate of many MOE reagents is only beginning to be mapped.

Open questions in chemical glycobiology.

Glycans are ubiquitous in biology, but their complex structure and biosynthesis have challenged research of their wide-ranging roles. Here, the authors comment on current trends on the role of chemical methodologies in the field of glycobiology.

Effect of extreme hot and cold weather on cause-specific hospitalizations in Sweden: A time series analysis.

Considering that several meteorological variables can contribute to weather vulnerability, the estimation of their synergetic effects on health is particularly useful. The spatial synoptic classification (SSC) has been used in biometeorological applications to estimate the effect of the entire suite of weather conditions on human morbidity and mortality. In this study, we assessed the relationships between extremely hot and dry (dry tropical plus, DT+) and hot and moist (moist tropical plus, MT+) weather types in summer and extremely cold and dry (dry polar plus, DP+) and cold and moist (moist polar, MP+) weather types in winter and cardiovascular and respiratory hospitalizations by age and sex.

Socio-economic and demographic factors associated with reproductive and child health preventive care in Mozambique: a cross-sectional study.

Background: Reproductive and child health interventions are essential to improving population health in Africa. In Mozambique, although some progress on reproductive and child health has been made, knowledge of social inequalities in health and health care is lacking.

Objective: To investigate socio-economic and demographic inequalities in reproductive and child preventive health care as a way to monitor progress towards universal health coverage.

Climate vulnerability of Swedish newborns: Gender differences and time trends of temperature-related neonatal mortality, 1880-1950.

Background: In resource-poor societies, neonatal mortality (death in the first 28 days of life) is usually very high. Young infants are particularly vulnerable to environmental health risks, which are modified by socioeconomic factors that change over time. We investigated the association between ambient temperature and neonatal mortality in northern Sweden during the demographic transition.

Generating orthogonal glycosyltransferase and nucleotide sugar pairs as next-generation glycobiology tools.

Protein glycosylation fundamentally impacts biological processes. Nontemplated biosynthesis introduces unparalleled complexity into glycans that needs tools to understand their roles in physiology. The era of quantitative biology is a great opportunity to unravel these roles, especially by mass spectrometry glycoproteomics.

Metabolic precision labeling enables selective probing of O-linked -acetylgalactosamine glycosylation.

Protein glycosylation events that happen early in the secretory pathway are often dysregulated during tumorigenesis. These events can be probed, in principle, by monosaccharides with bioorthogonal tags that would ideally be specific for distinct glycan subtypes. However, metabolic interconversion into other monosaccharides drastically reduces such specificity in the living cell.