Applied research won't flourish without basic science.

Three senior figures at the US National Institutes of Health explain why the agency remains committed to supporting basic science and research.

In vivo mapping of the mouse Galnt3-specific O-glycoproteome.

The UDP-N-acetylgalactosamine polypeptide:N-acetylgalactosaminyltransferase (GalNAc-T) family of enzymes initiates O-linked glycosylation by catalyzing the addition of the first GalNAc sugar to serine or threonine on proteins destined to be membrane-bound or secreted. Defects in individual isoforms of the GalNAc-T family can lead to certain congenital disorders of glycosylation (CDG). The polypeptide N-acetylgalactosaminyltransferase 3 (GALNT)3-CDG, is caused by mutations in GALNT3, resulting in hyperphosphatemic familial tumoral calcinosis due to impaired glycosylation of the phosphate-regulating hormone fibroblast growth factor 23 (FGF23) within osteocytes of the bone.

Quantitative mapping of the in vivo O-GalNAc glycoproteome in mouse tissues identifies GalNAc-T2 O-glycosites in metabolic disorder.

The family of GalNAc-Ts (GalNAcpolypeptide:N-Acetylgalactosaminyl transferases) catalyzes the first committed step in the synthesis of O-glycans, which is an abundant and biologically important protein modification. Abnormalities in the activity of individual GalNAc-Ts can result in congenital disorders of O-glycosylation (CDG) and influence a broad array of biological functions. How site-specific O-glycans regulate biology is unclear.

SPECIAL CONSIDERATIONS IN PEDIATRIC TRACHEOSTOMY - A NARRATIVE REVIEW.

Surgical tracheostomy is a life-saving procedure performed for emergent or expectant airway compromise. Morbidity in the pediatric population is higher than in adults due to smaller operating field, immaturity of tissues, anatomic specificities of the child's neck, or the presence of craniofacial dysmorphism. The procedure varies among surgeons regarding the position of the skin incision (vertical or horizontal), resection of the subcutaneous adipose tissue and isthmus of the thyroid gland, use of tracheal flaps, and use of maturation or stay sutures.

The NIH-led research response to COVID-19.

Investment, collaboration, and coordination have been key.

A novel role for GalNAc-T2 dependent glycosylation in energy homeostasis.

Objective: GALNT2, encoding polypeptide N-acetylgalactosaminyltransferase 2 (GalNAc-T2), was initially discovered as a regulator of high-density lipoprotein metabolism. GalNAc-T2 is known to exert these effects through post-translational modification, i.e.

Furin cleavage of the SARS-CoV-2 spike is modulated by -glycosylation.

The SARS-CoV-2 coronavirus responsible for the global pandemic contains a novel furin cleavage site in the spike protein (S) that increases viral infectivity and syncytia formation in cells. Here, we show that -glycosylation near the furin cleavage site is mediated by members of the GALNT enzyme family, resulting in decreased furin cleavage and decreased syncytia formation. Moreover, we show that -glycosylation is dependent on the novel proline at position 681 (P681).

Affirming NIH's commitment to addressing structural racism in the biomedical research enterprise.

NIH has acknowledged and committed to ending structural racism. The framework for NIH's approach, summarized here, includes understanding barriers; developing robust health disparities/equity research; improving its internal culture; being transparent and accountable; and changing the extramural ecosystem so that diversity, equity, and inclusion are reflected in funded research and the biomedical workforce.

Effect of High-Risk Obstructive Sleep Apnea on Clinical Outcomes in Adults with Coronavirus Disease 2019: A Multicenter, Prospective, Observational Clinical Trial.

Coronavirus disease (COVID-19) is an ongoing pandemic, in which obesity, hypertension, and diabetes have been linked to poor outcomes. Obstructive sleep apnea (OSA) is associated with these conditions and may influence the prognosis of adults with COVID-19. To determine the effect of OSA on clinical outcomes in patients with COVID-19.

Furin cleavage of the SARS-CoV-2 spike is modulated by O-glycosylation.

The SARS-CoV-2 coronavirus responsible for the global pandemic contains a unique furin cleavage site in the spike protein (S) that increases viral infectivity and syncytia formation. Here, we show that O-glycosylation near the furin cleavage site is mediated by specific members of the GALNT enzyme family and is dependent on the novel proline at position 681 (P681). We further demonstrate that O-glycosylation of S decreases furin cleavage.

Bortezomib induced pulmonary toxicity: a case report and review of the literature.

Bortezomib is widely used in the treatment of Multiple Myeloma. While the most common side effects are neurological and gastrointestinal related complications, severe pulmonary problems are rarely described. The present case is a 72-year old male with multiple myeloma, who received Lenalidomide, Bortezomib, and Dexamethasone (RVD) combination regimen.

Improved online LC-MS/MS identification of O-glycosites by EThcD fragmentation, chemoenzymatic reaction, and SPE enrichment.

O-glycosylation is a highly diverse and complex form of protein post-translational modification. Mucin-type O-glycosylation is initiated by the transfer of N-acetyl-galactosamine (GalNAc) to the hydroxyl group of serine, threonine and tyrosine residues through catalysis by a family of glycosyltransferases, the UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferases (E.C.

Appropriate use of tocilizumab in COVID-19 infection.

Objective: This study aimed to describe the effectiveness and optimum use of tocilizumab (TCZ) treatment by the support of clinical, laboratory and radiologic observations.

Methods: All patients were followed up in the hospital with daily interleukin-6 (IL-6), C-reactive protein (CRP), ferritin, d-dimer, full blood count, and procalcitonin. Thoracic computed tomography (CT) was performed on admission, when oxygen support was necessary, and seven days after TCZ started.

Differential splicing of the lectin domain of an -glycosyltransferase modulates both peptide and glycopeptide preferences.

Mucin-type -glycosylation is an essential post-translational modification required for protein secretion, extracellular matrix formation, and organ growth. -Glycosylation is initiated by a large family of enzymes (GALNTs in mammals and PGANTs in ) that catalyze the addition of GalNAc onto the hydroxyl groups of serines or threonines in protein substrates. These enzymes contain two functional domains: a catalytic domain and a C-terminal ricin-like lectin domain comprised of three potential GalNAc recognition repeats termed α, β, and γ.

Galnt11 regulates kidney function by glycosylating the endocytosis receptor megalin to modulate ligand binding.

Chronic kidney disease (CKD) affects more than 20 million Americans and ∼10% of the population worldwide. Genome-wide association studies (GWAS) of kidney functional decline have identified genes associated with CKD, but the precise mechanisms by which they influence kidney function remained largely unexplored. Here, we examine the role of 1 GWAS-identified gene by creating mice deficient for , which encodes a member of the enzyme family that initiates protein O-glycosylation, an essential posttranslational modification known to influence protein function and stability.

Precision Health: Bringing Oral Health into the Context of Overall Health.

Unprecedented advances in genomics, data science, and biotechnology have ushered in a new era of health care in which interventions are increasingly tailored to individual patients. Precision-based approaches extend to oral health, which is essential to overall health. Harnessing the full potential of precision oral health will depend on research to more fully understand the factors that underlie health and contribute to disease-including the human genome, microbiome, epigenome, proteome, and others.

The structure of the colorectal cancer-associated enzyme GalNAc-T12 reveals how nonconserved residues dictate its function.

Polypeptide acetylgalactosaminyl transferases (GalNAc-Ts) initiate mucin type -glycosylation by catalyzing the transfer of -acetylgalactosamine (GalNAc) to Ser or Thr on a protein substrate. Inactive and partially active variants of the isoenzyme GalNAc-T12 are present in subsets of patients with colorectal cancer, and several of these variants alter nonconserved residues with unknown functions. While previous biochemical studies have demonstrated that GalNAc-T12 selects for peptide and glycopeptide substrates through unique interactions with its catalytic and lectin domains, the molecular basis for this distinct substrate selectivity remains elusive.

The role of atopy in the pathogenesis of bleomycin pulmonary toxicity.

Introduction: Bleomycin pulmonary toxicity (BPT) is a potentially life-threatening consequence of bleomycin usage in patients. An overproduction of epithelium-derived cytokines, habitually linked to allergic inflammation, has been recently revealed in experimental models of BPT.

Methods: We assessed retrospectively our cohort of patients with Hodgkin Lymphoma treated with bleomycin between 2014 and 2016 for their demographic, clinical features, including BPT development, atopy status and risk factors for BPT.