Dr. Sonal Mahajan - Academia.edu (original) (raw)

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Papers by Dr. Sonal Mahajan

Advances in Experimental Medicine and Biology, 2018

F-type lectins are phylogenetically widespread albeit selectively distributed lectins with an Lfu... more F-type lectins are phylogenetically widespread albeit selectively distributed lectins with an Lfucose-binding sequence motif and an F-type lectin fold. Several F-type lectins from fishes have been extensively studied, and structural information is available for F-type lectin domains from fish and bacterial proteins. F-type lectins have been demonstrated to be involved in selfÀ/nonself-recognition and therefore have an important role in pathogen defense in many metazoan animals. F-type lectin domains also have been implicated in functions related to fertilization, protoplast regeneration, and bacterial virulence. We have recently analyzed and reported the taxonomic spread, phylogenetic distribution, architectural contexts, and sequence characteristics of prokaryotic and eukaryotic F-type lectin domains. Interestingly, while eukaryotic F-type lectin domains were frequently present as stand-alone domains, bacterial F-type lectin domains were mostly found co-occurring with enzymatic or nonenzymatic domains in diverse domain architectures, suggesting that the F-type lectin domain might be involved in targeting enzyme activities or directing other biological functions to distinct glycosylated niches in bacteria. We and others have probed the fine oligosaccharide-binding specificity of several F-type lectin domains. The currently available wealth of sequence, structural, and biochemical information about F-type lectin domains provides opportunities for the generation of designer lectins with improved binding strength and altered binding specificities. We discuss the prevalence, provenance, properties, peculiarities, and potential of F-type lectin domains for future applications in this review.

Biochemistry and Biophysics Reports, 2021

Chronic mucoid Pseudomonas aeruginosa infections are a major scourge in cystic fibrosis patients.... more Chronic mucoid Pseudomonas aeruginosa infections are a major scourge in cystic fibrosis patients. Mucoid P. aeruginosa displays structured alginate-rich biofilms that are resistant to antibiotics. Here, we have assessed the efficacy of a panel of alginate lyases in combating mucoid P. aeruginosa biofilms in cystic fibrosis. Albeit we could not demonstrate alginate degradation by alginate lyases in sputum, we demonstrate that the endotypic alginate lyases, CaAly (from Cellulophaga algicola) and VspAlyVI (from Vibrio sp. QY101) and the exotypic alginate lyases, FspAlyFRB (from Falsirhodobacterium sp. alg1), and SA1-IV (from Sphingomonas sp. A1), indeed inhibit biofilm formation by a mucoid P. aeruginosa strain isolated from the sputum of a cystic fibrosis patient with comparative effect to that of the glycoside hydrolase PslG, a promising candidate for biofilm treatment. We believe that these enzymes should be explored for in vivo efficacy in future studies.

Biochemical and Biophysical Research Communications, 2020

F-type lectins are typically L-fucose binding proteins with characteristic L-fucose-binding and c... more F-type lectins are typically L-fucose binding proteins with characteristic L-fucose-binding and calciumbinding sequence motifs, and an F-type lectin fold. An exception is Ranaspumin-4, an F-type lectin of the Tungra frog, Engystomops pustulosus. Ranaspumin-4 is D-galactose specific and does not bind to Lfucose although it has the conserved L-fucose binding sequence motif and shares overall sequence similarity with other F-type lectins. Here, we report the detailed glycan-binding profile of wild-type Ranaspumin-4 using hemagglutination inhibition assays, flow cytometry assays and enzyme-linked lectin assays, and identify residues important for D-galactose recognition using rational site-directed mutagenesis. We demonstrate that Ranaspumin-4 binds to terminal D-galactose in a or b linkage with preference for a1-3, a1-4, b1-3, and b1-4 linkages. Further, we find that a methionine residue (M31) in Ranaspumin-4 that occurs in place of a conserved Gln residue (in other F-type lectins), supports Dgalactose recognition. Resides Q42 and F156 also likely aid in D-galactose recognition.

IUBMB Life, 2020

S7, and S8) and 2 supplementary tables (Tables SI and SII) is being submitted as supplementary da... more S7, and S8) and 2 supplementary tables (Tables SI and SII) is being submitted as supplementary data for this manuscript.

Glycobiology, 2018

Individual lectin-carbohydrate interactions are usually of low affinity. However, high avidity is... more Individual lectin-carbohydrate interactions are usually of low affinity. However, high avidity is frequently attained by the multivalent presentation of glycans on biological surfaces coupled with the occurrence of high order lectin oligomers or tandem repeats of lectin domains in the polypeptide. F-type lectins are L-fucose binding lectins with a typical sequence motif, HX(26)RXDX(4)R/K, whose residues participate in L-fucose binding. We previously reported the presence of a few eukaryotic F-type lectin domains with partial sequence duplication that results in the presence of two L-fucose-binding sequence motifs. We hypothesized that such partial sequence duplication would result in greater avidity of lectin-ligand interactions. Inspired by this example from Nature, we attempted to engineer a bacterial F-type lectin domain from Streptosporangium roseum to attain avid binding by mimicking partial duplication. The engineered lectin demonstrated 12-fold greater binding strength than the wild-type lectin to multivalent fucosylated glycoconjugates. However, the affinity to the monosaccharide L-fucose in solution was similar and partial sequence duplication did not result in an additional functional L-fucose binding site. We also cloned, expressed and purified a Branchiostoma floridae F-type lectin domain with naturally occurring partial sequence duplication and confirmed that the duplicated region with the F-type lectin sequence motif did not participate in L-fucose binding. We found that the greater binding strength of the engineered lectin from S. roseum was instead due to increased oligomerization. We believe that this Nature-inspired strategy might be useful for engineering lectins to improve binding strength in various applications.

Biochemical and Biophysical Research Communications, 2017

F-type lectins are fucose binding lectins with characteristic fucose binding and calcium binding ... more F-type lectins are fucose binding lectins with characteristic fucose binding and calcium binding motifs. Although they occur with a selective distribution in viruses, prokaryotes and eukaryotes, most biochemical studies have focused on vertebrate F-type lectins. Recently, using sensitive bioinformatics search techniques on the non-redundant database, we had identified many microbial F-type lectin domains with diverse domain organizations. We report here the biochemical characterization of F-type lectin domains from Cyanobium sp. PCC 7001, Myxococcus hansupus and Leucothrix mucor. We demonstrate that while all these three microbial F-type lectin domains bind to the blood group H antigen epitope on fucosylated glycans, there are fine differences in their glycan binding specificity. Cyanobium sp. PCC 7001 F-type lectin domain binds exclusively to extended H type-2 motif, Myxococcus hansupus Ftype lectin domain binds to B, H type-1 and Lewis b motifs, and Leucothrix mucor F-type lectin domain binds to a wide range of fucosylated glycans, including A, B, H and Lewis antigens. We believe that these microbial lectins will be useful additions to the glycobiologist's toolbox for labeling, isolating and visualizing glycans.

2015 IEEE 8th International Conference on Software Testing, Verification and Validation (ICST), 2015

The energy consumption of mobile apps has become an important consideration for developers as the... more The energy consumption of mobile apps has become an important consideration for developers as the underlying mobile devices are constrained by battery capacity. Display represents a significant portion of an app's energy consumption-up to 60% of an app's total energy consumption. However, developers lack techniques to identify the user interfaces in their apps for which energy needs to be improved. This paper presents a technique for detecting display energy hotspots-user interfaces of a mobile app whose energy consumption is greater than optimal. The technique leverages display power modeling and automated display transformation techniques to detect these hotspots and prioritize them for developers. The evaluation of the technique shows that it can predict display energy consumption to within 14% of the ground truth and accurately rank display energy hotspots. Furthermore, the approach found 398 display energy hotspots in a set of 962 popular Android apps, showing the pervasiveness of this problem. For these detected hotspots, the average power savings that could be realized through better user interface design was 30%. Taken together, these results indicate that the approach represents a potentially impactful technique for helping developers to detect energy related problems and reduce the energy consumption of their mobile apps.

Proceedings of the 29th ACM/IEEE international conference on Automated software engineering, 2014

Presentation failures in web applications can negatively affect an application's usability and us... more Presentation failures in web applications can negatively affect an application's usability and user experience. To find such failures, testers must visually inspect the output of a web application or exhaustively specify invariants to automatically check a page's correctness. This makes finding presentation failures labor intensive and error prone. In this paper, we present a new automated approach for detecting and localizing presentation failures in web pages. To detect presentation failures, our approach uses image processing techniques to compare a web page and its oracle. Then, to localize the failures, our approach analyzes the page with respect to its visual layout and identifies the HTML elements likely to be responsible for the failure. We evaluated our approach on a set of real-world web applications and found that the approach was able to accurately detect failures and identify the faulty HTML elements.

2016 IEEE International Conference on Software Testing, Verification and Validation (ICST), 2016

Web applications can be easily made available to an international audience by leveraging framewor... more Web applications can be easily made available to an international audience by leveraging frameworks and tools for automatic translation and localization. However, these automated changes can distort the appearance of web applications since it is challenging for developers to design their websites to accommodate the expansion and contraction of text after it is translated to another language. Existing web testing techniques do not support developers in checking for these types of problems and manually checking every page in every language can be a labor intensive and error prone task. To address this problem, we introduce an automated technique for detecting when a web page's appearance has been distorted due to internationalization efforts and identifying the HTML elements or text responsible for the observed problem. In evaluation, our approach was able to detect internationalization problems in a set of 54 web applications with high precision and recall and was able to accurately identify the underlying elements in the web pages that led to the observed problem.