Cryptic sialic acid binding lectins on human blood leukocytes can be unmasked by sialidase treatment or cellular activation.

We recently reported that the sialic acid-specific binding sites of CD22 molecules on B cells are masked by endogenous ligands, and can be unmasked by sialidase treatment or cellular activation. Here, we show that many other human blood leukocyte types have endogenous sialic acid binding sites that can be unmasked by sialidase treatment. Truncation of sialic acid side chains on the soluble probes used for detection abolishes all binding, indicating the specificity of the interaction for the details of sialic acid structure. There is limited overlap between α2-6-and α2-3-sialic acid-specific binding sites, which are unmasked on monocytes, natural killer cells, a minority of mature T cells, neutrophils, and some cultured human leukemic cell lines. Activation with phorbol ester and calcium ionophore causes spontaneous exposure of some of the binding sites, occurring over a period of minutes on neutrophils and several hours on monocytes and U937 leukemia cells. Activation is accompanied by some evidence for desialylation of cell surface molecules. Thus, many human blood cells have specific binding sites for sialic acids, masked by endogenous sialylated ligands. Cellular activation can unmask these sites, possibly by the action of an endogenous sialidase. The nearly universal masking of such sites in unactivated blood cells could explain why many of these sialic acid-binding lectins have not been previously discovered. Similar considerations may apply to sialic acid binding lectins of other cell types and tissues

Correlation between HbA1c Levels and Depression in Children and Adolescents with Type 1 Diabetes

Background and purpose: Type 1 diabetes mellitus (T1DM) is a chronic disease with multiple long-term complications that could trigger depression. This study was performed to determine the relationship between HbA1C levels and depression in children and adolescents with T1DM. Materials and methods: This cross-sectional study was conducted in all children and adolescents with T1DM attending an endocrine clinic affiliated with Amirkola Children's Hospital, Iran 2018-2019. The patients aged 7-18 years old and at least 1.5 years had passed since the onset of their diabetes. Average of three HbA1c values (every six months) were considered and depression was measured using the Marques Children Depression Inventory. Results: Out of 100 patients with T1DM based on age-appropriate HbA1c, good, poor, and severe control of diabities were seen in 22%, 74%, and 4%, respectively. The risk of of depression in patients with poor control of diabities was 1.75 times higher than those with a good control of the disease, but this was not statistically significant (P=0.29). The risk of depression in children with illness duration of more than 6 years was 3.74 times higher than that in children with less than 6 years duration of the disease (P= 0.005). Conclusion: Better management of T1DM and HbA1c levels are needed to reduce the risk of depression in these patients

Structural Basis for Langerin Recognition of Diverse Pathogen and Mammalian Glycans through a Single Binding Site

Langerin mediates the carbohydrate-dependent uptake of pathogens by Langerhans cells in the first step of antigen presentation to the adaptive immune system. Langerin binds to an unusually diverse number of endogenous and pathogenic cell surface carbohydrates, including mannose-containing O-specific polysaccharides derived from bacterial lipopolysaccharides identified here by probing a microarray of bacterial polysaccharides. Crystal structures of the carbohydrate-recognition domain from human langerin bound to a series of oligomannose compounds, the blood group B antigen, and a fragment of β-glucan reveal binding to mannose, fucose, and glucose residues by Ca2+ coordination of vicinal hydroxyl groups with similar stereochemistry. Oligomannose compounds bind through a single mannose residue, with no other mannose residues contacting the protein directly. There is no evidence for a second Ca2+-independent binding site. Likewise, a β-glucan fragment, Glcβ1–3Glcβ1–3Glc, binds to langerin through the interaction of a single glucose residue with the Ca2+ site. The fucose moiety of the blood group B trisaccharide Galα1–3(Fucα1–2)Gal also binds to the Ca2+ site, and selective binding to this glycan compared to other fucose-containing oligosaccharides results from additional favorable interactions of the nonreducing terminal galactose, as well as of the fucose residue. Surprisingly, the equatorial 3-OH group and the axial 4-OH group of the galactose residue in 6SO4–Galβ1–4GlcNAc also coordinate Ca2+, a heretofore unobserved mode of galactose binding in a C-type carbohydrate-recognition domain bearing the Glu-Pro-Asn signature motif characteristic of mannose binding sites. Salt bridges between the sulfate group and two lysine residues appear to compensate for the nonoptimal binding of galactose at this site

Recognition of sialylated poly-N-acetyllactosamine chains on N- and O-linked glycans by human and avian influenza\u2005A virus hemagglutinins

Human influenza viruses are proposed to recognize sialic acids (pink diamonds) on glycans extended with poly-LacNAc chains (LacNAc=(yellow circle+blue square)). N- and O-linked glycans were extended with different poly-LacNAc chains with \u3b12-3- and \u3b12-6-linked sialic acids recognized by human and avian influenza viruses, respectively. The specificity of recombinant hemagglutinins (receptors in green) was investigated by using glycan microarray technology.Peer reviewed: YesNRC publication: Ye

Contribution of bone turnover markers (BTMs) and vitamin D to bone health in Iranian elderly women

PurposeWhile only a few postmenopausal women exhibit biochemical signs of hypovitaminosis D, it has been shown that vitamin D insufficiency has detrimental effects on the overall skeleton mineralization, bone turnover rate, and may be a significant risk factor for osteoporosis and fracture. We evaluated the concurrent effect of Vitamin D levels and biochemical markers of bone turnover on bone health of postmenopausal women.MethodsThe present study was conducted within the framework of the Bushehr Elderly Health (BEH) program, a population-based prospective cohort study being conducted in Bushehr, a southern province of Iran. In summary, 400 persons from participants of the second stage were selected; serum bone turnover markers (bone-specific alkaline phosphatase (bALP), amino-terminal procollagen propeptides of type I collagen (P1NP), osteocalcin (OC), tartrate-resistant acid phosphatase isoenzyme 5b (TRAP)) and vitamin D were measured. Vitamin D deficiency was defined as serum 25(OH) D below 20 ng/ml, and Bone health was considered in terms of Osteoporosis and degraded bone microarchitecture.ResultsThe number of partially or significantly degraded microstructure based on TBS was higher than the number of osteoporotic women based on BMD. Women with higher CTX levels were more prone to being degraded microarchitecture. Although we couldn't find any association between vitamin D deficiency and bone health, when we considered the vitamin D levels in univariable modelling, the effect of it was significant.ConclusionsIn this study, only CTX was found to be significantly correlated with TBS while BMD was associated with CTX, OC, and TRAP

Recent H3N2 Viruses Have Evolved Specificity for Extended, Branched Human-type Receptors, Conferring Potential for Increased Avidity

Human and avian influenza viruses recognize different sialic acid-containing receptors, referred to as human-type (NeuAcα2-6Gal) and avian-type (NeuAcα2-3Gal), respectively. This presents a species barrier for aerosol droplet transmission of avian viruses in humans and ferrets. Recent reports have suggested that current human H3N2 viruses no longer have strict specificity toward human-type receptors. Using an influenza receptor glycan microarray with extended airway glycans, we find that H3N2 viruses have in fact maintained human-type specificity, but they have evolved preference for a subset of receptors comprising branched glycans with extended poly-N-acetyl-lactosamine (poly-LacNAc) chains, a specificity shared with the 2009 pandemic H1N1 (Cal/04) hemagglutinin. Lipid-linked versions of extended sialoside receptors can restore susceptibility of sialidase-treated MDCK cells to infection by both recent (A/Victoria/361/11) and historical (A/Hong Kong/8/1968) H3N2 viruses. Remarkably, these human-type receptors with elongated branches have the potential to increase avidity by simultaneously binding to two subunits of a single hemagglutinin trimer