scispace - formally typeset
Search or ask a question
Author

Hari Prasad Dulal

Bio: Hari Prasad Dulal is an academic researcher from Cornell University. The author has contributed to research in topics: C-type lectin & Binding site. The author has an hindex of 5, co-authored 6 publications receiving 58 citations. Previous affiliations of Hari Prasad Dulal include Tokyo Medical and Dental University & Chitwan Medical College.

Papers
More filters
Journal ArticleDOI
TL;DR: Dectin-1 appears to be the first lectin-like molecule involved in the hetero-valent and specific recognition of characteristic N -glycans on antibodies.
Abstract: The core fucose, a major modification of N-glycans, is implicated in immune regulation, such as the attenuation of the antibody-dependent cell-mediated cytotoxicity of antibody drugs and the inhibition of anti-tumor responses via the promotion of PD-1 expression on T cells. Although the core fucose regulates many biological processes, no core fucose recognition molecule has been identified in mammals. Herein, we report that Dectin-1, a known anti-β-glucan lectin, recognizes the core fucose on IgG antibodies. A combination of biophysical experiments further suggested that Dectin-1 recognizes aromatic amino acids adjacent to the N-terminal asparagine at the glycosylation site as well as the core fucose. Thus, Dectin-1 appears to be the first lectin-like molecule involved in the heterovalent and specific recognition of characteristic N-glycans on antibodies.

24 citations

Journal ArticleDOI
TL;DR: It is suggested that the ligand-induced cooperative oligomer formation of Dectin-1 is physiologically relevant in sensing exogenous β-glucan and triggering intracellular signaling.
Abstract: Dectin-1 is a C-type lectin-like pattern recognition receptor that recognizes β(1-3)-glucans present on non-self pathogens. It is of great importance in innate immunity to understand the mechanism whereby Dectin-1 senses β(1-3)-glucans and induces intracellular signaling. In this study, we characterize the ligand binding and ligand-induced oligomerization of murine Dectin-1 using its C-type lectin-like domain (CTLD). Interaction of CTLD with laminarin, a β-glucan ligand, induced a tetramer of CTLD, as evidenced by size exclusion chromatography and multi-angle light scattering. Component analysis suggested a stoichiometry of four CTLD molecules bound to four laminarin molecules. Dimers and trimers of CTLD were not detected suggesting cooperative oligomerization. In order to map the amino acid residues of CTLD involved in β-glucan binding and domain oligomerization, we performed site-directed mutagenesis on surface-exposed and most conserved amino acid residues. Among the mutants examined, W221A, H223A and Y228A abolished oligomer formation. Since these residues are spatially arranged to form a hydrophobic groove, it is likely that W221, H223 and Y228 are directly involved in β-glucan binding. Interestingly, mutation of the residues on the other side of the hydrophobic groove, including Y141, R145 and E243, also exhibited reduced oligomer formation, suggesting involvement in protein-protein interactions guided by laminarin. Ligand titration using intrinsic tryptophan fluorescence revealed that wild-type CTLD binds laminarin cooperatively with a Hill coefficient of ~3, while the oligomer-reducing mutations, inside and outside the putative binding site abolish or decrease cooperativity. We suggest that the ligand-induced cooperative oligomer formation of Dectin-1 is physiologically relevant in sensing exogenous β-glucan and triggering intracellular signaling.

22 citations

Journal Article
TL;DR: Serum iron, total iron binding capacity (TIBC) and percentage transferrin saturation are calculated as the index of iron, and Malondialdehyde (MDA) is estimated as index of oxidant and vitamin C, vitamin E are measured asIndex of antioxidants.
Abstract: Diabetes mellitus is a common health problem of the world. Iron may be a part of the cause of the disease and its complications. Iron is a trace element which produces reactive oxygen species (ROS) participating through Fenton reaction and that ROS may be a cause to produce oxidative stress and further diabetic complications. The study aims to access the iron and its effect in producing oxidative stress in type 2 diabetic patients. Serum iron, total iron binding capacity (TIBC) and percentage transferrin saturation are calculated as the index of iron. Malondialdehyde (MDA) is estimated as index of oxidant and vitamin C, vitamin E are measured as index of antioxidants. This is a case control study conducted in the department of Biochemistry in collaboration with department of Medicine at B P Koirala Institute of Health Sciences (BPKIHS), Dharan, Nepal. 52 chronic type 2 diabetes mellitus patients and 52 age and sex matched normal healthy controls were included in the study. Plasma iron, TIBC, percentage transferrin saturation were found (89.14±30.50 μg/dL), (266.78±48.80 μg/dL), (36.61±14.31 %) in diabetic cases as compared to (83.98±24.19 μg/dL), (279.08±40.23 μg/dL), (31.05±10.98 %) of healthy controls. A signifi cant increase in MDA level (6.35±1.52 nmol/ml in cases and 4.18±1.12 nmol/ml in controls, p<0.001) and signifi cant decrease in vitamin C (0.85±0.19 mg/dL in cases and 1.28±0.21mg/dL in controls, p< 0.001) and vitamin E (0.85±0.25 mg/dL in cases and 1.34±0.38mg/dL in controls, p<0.001) were observed.

14 citations

Journal ArticleDOI
TL;DR: Results indicate that fusing GB1 to the N-terminus of mouse Dectin-1 domain advantageously increases yield and solubility, allows retention of native structure, and that the site of fusion is critical.

12 citations

Journal ArticleDOI
TL;DR: The pros and cons of currently available diagnostic tests for enteric fever, the advancement of research toward improved diagnostic tests, and the challenges of discovering new ideal biomarkers and tests are discussed.
Abstract: Enteric fever is a life-threatening systemic febrile disease caused by Salmonella enterica serovars Typhi and Paratyphi (S. Typhi and S. Paratyphi). Unfortunately, the burden of the disease remains high primarily due to the global spread of various drug-resistant Salmonella strains despite continuous advancement in the field. An accurate diagnosis is critical for effective control of the disease. However, enteric fever diagnosis based on clinical presentations is challenging due to overlapping symptoms with other febrile illnesses that are also prevalent in endemic areas. Current laboratory tests display suboptimal sensitivity and specificity, and no diagnostic methods are available for identifying asymptomatic carriers. Several research programs have employed systemic approaches to identify more specific biomarkers for early detection and asymptomatic carrier detection. This review discusses the pros and cons of currently available diagnostic tests for enteric fever, the advancement of research toward improved diagnostic tests, and the challenges of discovering new ideal biomarkers and tests.

12 citations


Cited by
More filters
Journal ArticleDOI
TL;DR: Pattern recognition receptors (PRRs) are a class of receptors that can directly recognize the specific molecular structures on the surface of pathogens, apoptotic host cells, and damaged senescent cells as mentioned in this paper.
Abstract: Pattern recognition receptors (PRRs) are a class of receptors that can directly recognize the specific molecular structures on the surface of pathogens, apoptotic host cells, and damaged senescent cells. PRRs bridge nonspecific immunity and specific immunity. Through the recognition and binding of ligands, PRRs can produce nonspecific anti-infection, antitumor, and other immunoprotective effects. Most PRRs in the innate immune system of vertebrates can be classified into the following five types based on protein domain homology: Toll-like receptors (TLRs), nucleotide oligomerization domain (NOD)-like receptors (NLRs), retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs), C-type lectin receptors (CLRs), and absent in melanoma-2 (AIM2)-like receptors (ALRs). PRRs are basically composed of ligand recognition domains, intermediate domains, and effector domains. PRRs recognize and bind their respective ligands and recruit adaptor molecules with the same structure through their effector domains, initiating downstream signaling pathways to exert effects. In recent years, the increased researches on the recognition and binding of PRRs and their ligands have greatly promoted the understanding of different PRRs signaling pathways and provided ideas for the treatment of immune-related diseases and even tumors. This review describes in detail the history, the structural characteristics, ligand recognition mechanism, the signaling pathway, the related disease, new drugs in clinical trials and clinical therapy of different types of PRRs, and discusses the significance of the research on pattern recognition mechanism for the treatment of PRR-related diseases.

306 citations

Journal Article
TL;DR: Glycated material was found to function both as a reductant and an oxidant and a possible mechanism by which superoxide is produced is proposed and results may give a clue to diabetic complications.
Abstract: Nonenzymatically glycated human serum albumin and glycated poly-lysine(Lys) in vitro brought about the reduction of nitroblue tetrazolium and ferricytochrome c at pH 9.06 and pH 7.8, respectively. This reduction was inhibited partially by superoxide dismutase (SOD). Glycated poly-Lys caused the oxidation of NADH in the presence of LDH at pH 7.0 which was completely inhibited by SOD. Glycated material was found to function both as a reductant and an oxidant. The reactivity of glycated material is discussed and a possible mechanism by which superoxide is produced is proposed. Results may give a clue to diabetic complications.

299 citations

Journal ArticleDOI
TL;DR: In this paper, a review summarizes recent findings regarding the physiological functionalities of β-glucans and details the action mechanisms of βglucants upon the present knowledge, and the prospects for future research on these topics are also discussed.
Abstract: Background β-Glucans are polysaccharides constructed of glucose monomers linked by β-glucosidic bonds, which mainly exist in cereals (barley and oat), yeast and mushrooms. Some physiological functionalities of β-glucans have been confirmed, consequently, their development and utilization in the biomedical, pharmaceutical, food, and cosmetic industries have received increasing interest. Foods and dietary supplements containing β-glucans are very popular. Scope and approach This review summarizes recent findings regarding the physiological functionalities of β-glucans and details the action mechanisms of β-glucans upon the present knowledge. The prospects for future research on these topics are also discussed. Key findings and conclusions β-Glucans are effective in many aspects of human health, including cancer prevention, reducing glycemia and serum cholesterol, anti-inflammation, as well as improving immunity. The modification of β-glucans contributes to better solubility, viscosity and gelation, which can change the bioactivities of β-glucans. The action mechanisms of β-glucans and their derivatives are considered to be mainly mediated by some cytokines and hormones in subjects. Human health is supported by various mechanism researches. Although certain action mechanisms remain unclear, the clarification of how β-glucans exhibit biological effects is beneficial for our understanding of complicated biochemical reaction in living organisms.

91 citations

Journal ArticleDOI
TL;DR: Reading this review will gain a fundamental understanding why carbohydrates form the third alphabet of life, joining the ranks of nucleotides and amino acids, and will also become aware of the importance of cellular communication via glycan-lectin recognition.
Abstract: Ubiquitous occurrence in Nature, abundant presence at strategically important places such as the cell surface and dynamic shifts in their profile by diverse molecular switches qualifies the glycans to serve as versatile biochemical signals. However, their exceptional structural complexity often prevents one noting how simple the rules of objective-driven assembly of glycan-encoded messages are. This review is intended to provide a tutorial for a broad readership. The principles of why carbohydrates meet all demands to be the coding section of an information transfer system, and this at unsurpassed high density, are explained. Despite appearing to be a random assortment of sugars and their substitutions, seemingly subtle structural variations in glycan chains by a sophisticated enzymatic machinery have emerged to account for their specific biological meaning. Acting as ‘readers’ of glycan-encoded information, carbohydrate-specific receptors (lectins) are a means to turn the glycans’ potential to serve as signals into a multitude of (patho)physiologically relevant responses. Once the far-reaching significance of this type of functional pairing has become clear, the various modes of spatial presentation of glycans and of carbohydrate recognition domains in lectins can be explored and rationalized. These discoveries are continuously revealing the intricacies of mutually adaptable routes to achieve essential selectivity and specificity. Equipped with these insights, readers will gain a fundamental understanding why carbohydrates form the third alphabet of life, joining the ranks of nucleotides and amino acids, and will also become aware of the importance of cellular communication via glycan–lectin recognition.

72 citations

Journal ArticleDOI
TL;DR: Regulation of a gene expression profile typical of a signalling pathway associated with CLR activation and, the identification of several candidate β-glucan receptors, suggest that immune-modulatory effects of β- glucan in carp macrophages could be a result of signalling mediated by a member of the CLR family.
Abstract: Immune-modulatory effects of β-glucans are generally considered beneficial to fish health. Despite the frequent application of β-glucans in aquaculture practice, the exact receptors and downstream signalling remains to be described for fish. In mammals, Dectin-1 is a member of the C-type lectin receptor (CLR) family and the best-described receptor for β-glucans. In fish genomes, no clear homologue of Dectin-1 could be identified so far. Yet, in previous studies we could activate carp macrophages with curdlan, considered a Dectin-1-specific β-(1,3)-glucan ligand in mammals. It was therefore proposed that immune-modulatory effects of β-glucan in carp macrophages could be triggered by a member of the CLR family activating the classical CLR signalling pathway, different from Dectin-1. In the current study, we used primary macrophages of common carp to examine immune modulation by β-glucans using transcriptome analysis of RNA isolated 6 h after stimulation with two different β-glucan preparations. Pathway analysis of differentially expressed genes (DEGs) showed that both β-glucans regulate a comparable signalling pathway typical of CLR activation. Carp genome analysis identified 239 genes encoding for proteins with at least one C-type Lectin Domains (CTLD). Narrowing the search for candidate β-glucan receptors, based on the presence of a conserved glucan-binding motif, identified 13 genes encoding a WxH sugar-binding motif in their CTLD. These genes, however, were not expressed in macrophages. Instead, among the β-glucan-stimulated DEGs, a total of six CTLD-encoding genes were significantly regulated, all of which were down-regulated in carp macrophages. Several candidates had a protein architecture similar to Dectin-1, therefore potential conservation of synteny of the mammalian Dectin-1 region was investigated by mining the zebrafish genome. Partial conservation of synteny with a region on the zebrafish chromosome 16 highlighted two genes as candidate β-glucan receptor. Altogether, the regulation of a gene expression profile typical of a signalling pathway associated with CLR activation and, the identification of several candidate β-glucan receptors, suggest that immune-modulatory effects of β-glucan in carp macrophages could be a result of signalling mediated by a member of the CLR family.

47 citations