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Biomedical subjects

Ajay Bhatia

Publications and source records attributed to Ajay Bhatia.

8 recordsLinked to original sources

CHITRA: an interactive visualization tool for comparative genomic rearrangement analysis.

MOTIVATION: The increasing availability of chromosome-scale genome assemblies has fuelled a renewed interest in studying chromosomal evolution and rearrangements. Synteny visualization plays a critical role in understanding genome organization, structural variations, and evolutionary relationships. However, existing tools often have steep learning curves, produce static plots, or are limited in their ability to analyse multiple genomes simultaneously. There is a growing need for an intuitive and interactive visualization tool that can effectively explore syntenic relationships and chromosomal rearrangements. RESULTS: Here, we present CHITRA, a web-based interactive tool designed to visualize synteny blocks, chromosomal rearrangements, and breakpoints in both linear and circular styles. CHITRA-enables real-time exploration of genome structural variations with an intuitive graphical interface, customizable visualization options, and high-resolution export capabilities for publication-ready figures. The tool supports chromosome- and scaffold-level assemblies and allows users to filter, highlight, and interactively examine syntenic relationships. AVAILABILITY AND IMPLEMENTATION: CHITRA is freely available at https://chitra.bioinformaticsonline.com/, with comprehensive documentation at https://chitra.bioinformaticsonline.com/docs. The source code is open-source and accessible on GitHub at https://github.com/pranjalpruthi/CHITRA.

Journal Article↗

How influenza's neuraminidase promotes virulence and creates localized lung mucosa immunodeficiency.

Neuraminidase (NA) is an enzyme coded for by the genome of influenza critical for its pathogenicity and survival. Three currently accepted roles for this NA in promoting influenza virulence are: 1. NA cleaves newly formed virus particles from the host cell membrane. Without NA, newly formed virus would remain attached to the cell within which it was produced. 2. NA prevents newly released virus particles from aggregating to each other, preventing clumping that would reduce dissemination. 3. NA promotes viral penetration of sialic acid-rich mucin that bathes and protects respiratory epithelium through which the virus must spread and replicate. We outline here previous research evidence of two further, albeit hypothetical, functions of NA that together could cause disruption the mucosa-IgA axis, creating localized partial immunosuppressed state, enhancing both influenza infection itself and secondary bacterial pneumonia: 4. IgA provides primary immunoglobulin defense of mucosal surfaces. The hinge region of IgA is normally sialylated. IgA denuded of sialic acid is recognized, bound, and cleared by hepatic asialoglycoprotein receptor (ASGPR). Thus, IgA exposed to free NA would be so denuded and have increased hepatic clearance. 5. NA removes sialic acid moieties from mucosa-residing gamma/delta T cells or IgA producing B cells. Previous work indicates desialylation of these lymphocytes' outer cell membrane results in altered homing, to bone marrow, away from mucosa. Currently marketed NA inhibitors oseltamivir (Tamiflu) and zanamivir (Relenza) are FDA approved in USA for influenza prophylaxis and treatment. These NA inhibitors lower incidence of secondary bacterial infection in cases where an influenza infection occurs despite their use. Moreover, they are ameliorative in patients with secondary bacterial infections treated with antibiotics, a benefit that surpasses the treatment of antibiotics alone. We interpret these last two points as indicating our ascription of localized immunosuppression to influenza's NA could be correct and lead to new treatments of infections generally.

Animals↗

Variable expression of immunoreactive surface proteins of Propionibacterium acnes.

Despite accumulating data implicating Propionibacterium acnes in a variety of diseases, its precise role in infection remains to be determined. P. acnes antigen-specific CD4(+) T cells are present in early inflamed acne lesions and may be involved in the inflammatory response; however, little is known about the specific antigens involved. In this study, B cell and T cell antigens from P. acnes expression libraries were cloned and evaluated and the four predominant proteins identified were investigated. Two of these antigens share some homology with an M-like protein of Streptococcus equi and have dermatan-sulphate-binding activity (PA-25957 and 5541). The remaining two antigens, PA-21693 and 4687, are similar to the product of the Corynebacterium diphtheriae htaA gene from the hmu ABC transport locus, although only one of these (PA-21693) is encoded within an hmu-like operon and conserved amongst a range of clinical isolates. All four proteins contain an LPXTG motif, although only PA-21693 contains a characteristic sortase-sorting signal. Variation in the expression of PA-4687, 25957 and 5541 is evident amongst clinical isolates and is generated both by frameshifts associated with the putative signal peptide and by variable numbers of repeat regions toward the carboxy-terminus, potentially generating heterogeneity of molecular mass and antigenic variation. In addition, in the case of PA-25957, a frameshift in a C-rich region at the extreme carboxy-terminus eliminates the LPXTG motif in some isolates. For the dermatan-sulphate-binding PA-25957, IgG1 antibody in serum from acne-positive donors was shown to be specific for the amino-terminal region of the protein, which also contains a CD4(+) T cell epitope. In contrast, serum from acne-negative donors shows an IgG2 and IgG3 antibody subclass response to the carboxy-terminal region. These data have implications for the potential role of P. acnes in inflammatory acne and other diseases.

Acne Vulgaris↗

CAMP factor homologues in Propionibacterium acnes: a new protein family differentially expressed by types I and II.

Analysis of the draft genome sequence of the opportunistic pathogen Propionibacterium acnes type strain NCTC 737 (=ATCC 6919) revealed five genes with sequence identity to the co-haemolytic Christie-Atkins-Munch-Peterson (CAMP) factor of Streptococcus agalactiae. The predicted molecular masses for the expressed proteins ranged from 28 to 30 kDa. The genes were present in each of the three recently identified recA-based phylogenetic groupings of P. acnes (IA, IB and II), as assessed by PCR amplification. Conserved differences in CAMP factor gene sequences between these three groups were also consistent with their previous phylogenetic designations. All type IA, IB and II isolates were positive for the co-haemolytic reaction on sheep blood agar. Immunoblotting and silver staining of SDS-PAGE gels, however, revealed differential protein expression of CAMP factors amongst the different groups. Type IB and II isolates produced an abundance of CAMP factor 1, detectable by specific antibody labelling and silver staining of SDS-PAGE gels. In contrast, abundant CAMP factor production was lacking in type IA isolates, although larger amounts of CAMP factor 2 were detectable by immunoblotting compared with type II isolates. While the potential role of the abundant CAMP factor 1 in host colonization or virulence remains to be determined, it should be noted that the type strain of P. acnes used in much of the published literature is a type IA isolate and is, therefore, lacking in this attribute.

Animals↗

Propionibacterium acnes types I and II represent phylogenetically distinct groups.

Although two phenotypes of the opportunistic pathogen Propionibacterium acnes (types I and II) have been described, epidemiological investigations of their roles in different infections have not been widely reported. Using immunofluorescence microscopy with monoclonal antibodies (MAbs) QUBPa1 and QUBPa2, specific for types I and II, respectively, we investigated the prevalences of the two types among 132 P. acnes isolates. Analysis of isolates from failed prosthetic hip implants (n = 40) revealed approximately equal numbers of type I and II organisms. Isolates from failed prosthetic hip-associated bone (n = 6) and tissue (n = 38) samples, as well as isolates from acne (n = 22), dental infections (n = 8), and skin removed during surgical incision (n = 18) were predominately of type I. A total of 11 (8%) isolates showed atypical MAb labeling and could not be conclusively identified. Phylogenetic analysis of P. acnes by nucleotide sequencing revealed the 16S rRNA gene to be highly conserved between types I and II. In contrast, sequence analysis of recA and a putative hemolysin gene (tly) revealed significantly greater type-specific polymorphisms that corresponded to phylogenetically distinct cluster groups. All 11 isolates with atypical MAb labeling were identified as type I by sequencing. Within the recA and tly phylogenetic trees, nine of these isolates formed a cluster distinct from other type I organisms, suggesting a further phylogenetic subdivision within type I. Our study therefore demonstrates that the phenotypic differences between P. acnes types I and II reflect deeper differences in their phylogeny. Furthermore, nucleotide sequencing provides an accurate method for identifying the type status of P. acnes isolates.

Animals↗

Chondrosarcoma in association with primary hyperparathyroidism.

We describe two female patients, 66 and 36 years of age, with both primary hyperparathyroidism and chondrosarcoma. Case 1 had a chondrosarcoma of the right scapula, and case 2 had chondrosarcoma of the left proximal tibia. Both patients underwent surgical resection of their chondrosarcoma and subsequent parathyroid surgery. Histological analysis of the excised parathyroid in case 1 showed a parathyroid carcinoma and in case 2 showed a parathyroid adenoma. Including these two patients, there is now a total of six cases that have been reported in the literature describing the association between hyperparathyroidism and bone malignancy. We believe that this small number makes it unlikely that there is an association between these two conditions, although we speculate that there may be an underlying genetic basis.

Adult↗