University of California, Davis

education📍 Davis, United States
University of California, Davis
5
Alpha-gal Syndrome Publications
4
Alpha-gal Syndrome Researchers

Associated Institutions

Veterinary Medical Teaching Hospital
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University of California System
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NeuroMab
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University of California Davis Medical Center
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UC Davis Health
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Publications

Assessing the potential risk of lone star tick, Amblyomma americanum, establishment in California.

Foley J, Rubino F, Kam D, Lozano K
Ticks and tick-borne diseases •

The lone star tick (LST), Amblyomma americanum, is an aggressive human biter and important vector of the causative agents of tick-borne diseases. As geographic ranges of multiple Amblyomma species rapidly expand due to habitat changes and human and other animal movement patterns, there are concerns for establishment of LST in US states with suitable climates, such as California, especially given a dearth in gaps in tick surveillance. Importantly, previous niche modeling confirmed habitat in California along the length of the coast and coast range mountains. We sought data on LSTs and LST risk from 30 different entities including companies that identify and test ticks, natural history and entomology museums and collections, experts, and large databases. These queries and published records yielded records of 76 LSTs from California as well as two Amblyomma cajennense sensu lato, one Amblyomma sabanerae, one Amblyomma maculatum, and five Amblyomma dissimile. Among LSTs, there were 18 adult females, ten males, 13 adults for which sex was not recorded, 22 nymphs, two larvae, and 11 with no stage data. LSTs were recorded only during late spring through late summer, with all three feeding stages superimposed temporally. Active surveillance was conducted at nine sites considered high-risk due to earlier records of LSTs or high probability of establishment on niche modeling, using tick flagging, monitoring ovine and cervid hosts, and circulating a flier; no LSTs were recovered in this activity. We assessed risk for establishment of LSTs in California using invasion theory, prior niche modeling, literature review of ecological constraints on LSTs within their current range, data acquired in retrospective and prospective segments of this study, and expert consultation. Elevated risk is expected particularly along coastal California. Although some of these ticks likely were transported from out of state endemic regions, the findings of 76 LSTs, including all three feeding stages, in multiple counties raises concern that establishment in the future could occur in California.

Quantitative and qualitative changes in anti-Neu5Gc antibody response following rabbit anti-thymocyte IgG induction in kidney allograft recipients.

Rousse J, Salama A, Leviatan Ben-Arye S, Hruba P, Slatinska J, et al.
European journal of clinical investigation •

Antibodies of non-human mammals are glycosylated with carbohydrate antigens, such as galactose-α-1-3-galactose (α-Gal) and N-glycolylneuraminic acid (Neu5Gc). These non-human carbohydrate antigens are highly immunogenic in humans due to loss-of-function mutations of the key genes involved in their synthesis. Such immunogenic carbohydrates are expressed on therapeutic polyclonal rabbit anti-human T-cell IgGs (anti-thymocyte globulin; ATG), the most popular induction treatment in allograft recipients. To decipher the quantitative and qualitative response against these antigens in immunosuppressed patients, particularly against Neu5Gc, which may induce endothelial inflammation in both the graft and the host. We report a prospective study of the antibody response against α-Gal and Neu5Gc-containing glycans following rabbit ATG induction compared to controls. We show a drop in the overall levels of anti-Neu5Gc antibodies at 6 and 12 months post-graft compared to the pre-existing levels due to the major early immunosuppression. However, in contrast, in a cross-sectional study there was a highly significant increase in anti-Neu5Gc IgGs levels at 6 months post-graft in the ATG-treated compared to non-treated patients(P = 0.007), with a clear hierarchy favouring anti-Neu5Gc over anti-Gal response. A sialoglycan microarray analysis revealed that the increased anti-Neu5Gc IgG response was still highly diverse against multiple different Neu5Gc-containing glycans. Furthermore, some of the ATG-treated patients developed a shift in their anti-Neu5Gc IgG repertoire compared with the baseline, recognizing different patterns of Neu5Gc-glycans. In contrast to Gal, Neu5Gc epitopes remain antigenic in severely immunosuppressed patients, who also develop an anti-Neu5Gc repertoire shift. The clinical implications of these observations are discussed.

Structural characterization and antidiabetic potential of a novel heteropolysaccharide from Grifola frondosa via IRS1/PI3K-JNK signaling pathways.

Chen Y, Liu Y, Sarker MMR, Yan X, Yang C, et al.
Carbohydrate polymers •

A novel heteropolysaccharide from Grifola frondosa named GFP-W has been isolated and purified by DEAE Sephadex A-52 chromatography. Gas chromatography, fourier transform infrared spectroscopy, one-dimensional (H- and C-) and two-dimensional (H-H COSY, H-C HSQC, and H-C HMBC) nuclear magnetic resonance spectroscopy were used to characterize its structure. The average molecular weight of GFP-W was 66.1 kDa. GFP-W mainly contained four kinds of linkage type units as β-D-GlcpA→, 1,2,6-α-Gal, →2)-α-Manp→, and →3)-α-L-Fucp-(1→. It could significantly increase the uptake of glucose in dexamethasone induced insulin resistant HepG2 cells by improving the mRNA and protein expression of insulin receptor substrate 1, phosphatidylinositol-3-kinase, and glucose transporter 4 upregulation and c-Jun N-terminal Kinase 1 downregulation. Moreover, antidiabetic activities of GFP-W were associated with significant changes in the extent of protein lysine acetylation, crotonylation, and succinylation levels. Our results provide a new hypoglycemic therapeutic role and an in-depth analysis on molecular mechanisms upon polysaccharides from G. frondosa.

Highly efficient chemoenzymatic synthesis and facile purification of α-Gal pentasaccharyl ceramide Galα3nLcβCer.

Santra A, Li Y, Yu H, Slack TJ, Wang PG, et al.
Chemical communications (Cambridge, England) •

A highly efficient chemoenzymatic method for synthesizing glycosphingolipids using α-Gal pentasaccharyl ceramide as an example is reported here. Enzymatic extension of the chemically synthesized lactosyl sphingosine using efficient sequential one-pot multienzyme (OPME) reactions allowed glycosylation to be carried out in aqueous solutions. Facile C18 cartridge-based quick (<30 minutes) purification protocols were established using minimal amounts of green solvents (CHCN and HO). Simple acylation in the last step led to the formation of the target glycosyl ceramide in 4 steps with an overall yield of 57%.

Identification of the binding roles of terminal and internal glycan epitopes using enzymatically synthesized N-glycans containing tandem epitopes.

Wu Z, Liu Y, Ma C, Li L, Bai J, et al.
Organic & biomolecular chemistry •

Glycans play diverse roles in a wide range of biological processes. Research on glycan-binding events is essential for learning their biological and pathological functions. However, the functions of terminal and internal glycan epitopes exhibited during binding with glycan-binding proteins (GBPs) and/or viruses need to be further identified. Therefore, a focused library of 36 biantennary asparagine (Asn)-linked glycans with some presenting tandem glycan epitopes was synthesized via a combined Core Isolation/Enzymatic Extension (CIEE) and one-pot multienzyme (OPME) synthetic strategy. These N-glycans include those containing a terminal sialyl N-acetyllactosamine (LacNAc), sialyl Lewis x (sLe) and Siaα2-8-Siaα2-3/6-R structures with N-acetylneuraminic acid (Neu5Ac) or N-glycolylneuraminic acid (Neu5Gc) sialic acid form, LacNAc, Lewis x (Le), α-Gal, and Galα1-3-Le; and tandem epitopes including α-Gal, Le, Galα1-3-Le, LacNAc, and sialyl LacNAc, presented with an internal sialyl LacNAc or 1-2 repeats of an internal LacNAc or Le component. They were synthesized in milligram-scale, purified to over 98% purity, and used to prepare a glycan microarray. Binding studies using selected plant lectins, antibodies, and viruses demonstrated, for the first time, that when interpreting the binding between glycans and GBPs/viruses, not only the structure of the terminal glycan epitopes, but also the internal epitopes and/or modifications of terminal epitopes needs to be taken into account.