Biology subjects

Khan, G.

Publications and source records attributed to Khan, G..

5 recordsLinked to original sources

bioRxiv2025

Levamisole-Mediated Suppression of B-Cell Proliferation and Antibody Production Reveals Mechanistic Insights into Idiopathic Nephrotic Syndrome Therapy

Levamisole (LMS) is a small imidazole derivative with immunomodulatory properties. Despite its longstanding clinical use in Idiopathic Nephrotic Syndrome (INS), the mechanisms underlying its immune-regulating effects remain poorly defined. In this study, we investigated the in vitro effects of LMS treatment on human B-cells, and in patients included from the LEARNS (LEvamisole as Adjuvant therapy to Reduce relapses of Nephrotic Syndrome) clinical trial. In vitro experiments showed that LMS directly suppresses activation and proliferation in both T-cell dependent and T-cell independent stimulated B-cells, without inducing cytotoxicity. In agreement, transcriptomic profiling demonstrated downregulation of cell cycle-associated genes and genes involved in immunoglobulin synthesis, while genes involved in terminal B-cell differentiation were upregulated, including SLAMF7. Consistently, LMS treatment decreased immunoglobulin expression and secretion while simultaneously inducing the expression of factors associated with a more terminal B-cell phenotype (CD138/CD319). Flowcytometry analysis of blood samples from LMS-treated INS patients revealed reduced circulating B-cell counts. Collectively, these data suggest that LMS acts as a potent modulator of B-cell function that inhibits proliferation and immunoglobulin synthesis, providing mechanistic support for its therapeutic efficacy in INS management.

immunology↗

bioRxiv2024

Prevalence and diversity of Helicobacter species in captive wild carnivores, and their implications for conservation management of endangered species

Helicobacter species colonize the gastrointestinal tract of various hosts, and have always been of interest due to their potential zoonotic transmission and impact on health of humans and animals. Comprehensive studies involving wild animals from different locations are lacking, hindering our understanding of their natural host range, prevalence, and genetic diversity. Here we investigated the prevalence and genetic diversity of Helicobacter species in thirteen wild carnivore species across twenty-two zoos and rescue centers in India by targeting partial 16S rRNA gene. We used sequences obtained from positive samples for phylogenetic analysis, and further evaluated factors influencing Helicobacter prevalence with generalised linear mixed models. We analysed 985 faecal samples of which 286 (29%) tested positive for Helicobacter, spanning all the host species included in this study. Helicobacter prevalence is strongly related to host species and location, and varied from 7.3% in common leopard to 80% in Indian fox. Phylogenetic analysis identified 59 unique genotypes clustered into 11 groups of three major Helicobacter types: enterohepatic, gastric, and unsheathed. Diverse Helicobacter species associated with diseases in humans and domestic animals were observed, such as H. canis, H. bilis, along with several novel strains/ species which require formal classification. Overall, this study highlights the wide occurrence and high genetic diversity of Helicobacter species in captive wild carnivores in India. Our findings underscore the need for regular health assessments in captive facilities to monitor Helicobacter infections, which could impact the health and management of endangered species. Future research should explore Helicobacter presence in biotic and abiotic factors in zoo and free-ranging populations following One Health approaches.

microbiology↗

bioRxiv2024

Implementation of pupylation-based proximity labelling in plant biology reveals regulatory factors in cellulose biosynthesis

Knowledge about how and where proteins interact provides a pillar for cell biology. Biotin-related proximity labelling approaches are efficiently monitoring protein interactions but may have labelling-related drawbacks. Here, we introduce pupylation-based proximity labelling (PUP-IT) as a tool for protein interaction detection in plant biology. We show that PUP-IT readily confirmed and extended protein interactions for several known protein complexes, across different types of plant systems. To further demonstrate the power of PUP-IT, we used the system to identify protein interactions of the protein complex that underpin cellulose synthesis in plants. Apart from known complex components, we identified the ARF-GEF BEN1 (BFA-VISUALIZED ENDOCYTIC TRAFFICKING DEFECTIVE1). We show that BEN1 contributes to cellulose synthesis by regulating the trafficking of the cellulose synthesis protein complex between the trans-Golgi network and the plasma membrane. Our results, therefore, introduce PUP-IT as a new and powerful proximity labelling system to identify protein interactions in plant cells.

plant biology↗

bioRxiv2021

A DUF1068 protein acts as a pectin biosynthesis scaffold and maintains Golgi morphology and cell adhesion in Arabidopsis.

Adjacent plant cells are connected by specialized cell wall regions, called middle lamellae, which influence critical agricultural characteristics, including fruit ripening and organ abscission. Middle lamellae are enriched in pectin polysaccharides, specifically homogalacturonan (HG). Here, we identify a plant-specific Arabidopsis DUF1068 protein, called NKS1, that is required for middle lamellae integrity and cell adhesion. NKS1 localises to the Golgi apparatus and loss of the protein results in changes to Golgi structure and function. The nks1 mutants also display HG deficient phenotypes, including reduced seedling growth, changes to cell wall composition, and tissue integrity defects. These phenotypes are identical to those of the HG deficient mutants qua1 and qua2. Notably, NKS1 physically interacts with both QUA1 and QUA2, and genetic interaction analyses reveal that they work in the same pathway. Based on these results we propose that NKS1 works as a scaffold for HG synthesis and that such scaffolding is important to support Golgi function and the organization of the pectin synthesis machinery.

plant biology↗

bioRxiv2020

Incongruent phylogenies and its implications for the study of diversification, taxonomy and genome size evolution of Rhododendron (Ericaceae)

PREMISERhododendron L. (Ericaceae Juss.), is the most species-rich genus of woody flowering plants with > 1000 species. Despite the interest in the genus and numerous previous phylogenetic analysis, the infrageneric classification for the genus is still debated, partly due to its huge diversity, partly due to homoplasy in key characters and partly due to incongruence between phylogenetic markers. Here, we provide a broad coverage of representative species of all Rhododendron subgenera, sections, and most subsections to resolve its infrageneric phylogeny or highlight areas of incongruence, support previous analyses of diversification patterns and establish a relationship between genome size evolution and its diversification. METHODSWe generated sequences of two plastid (trnK and trnL-F) and two nuclear (ITS and rpb2-i) markers for a total of 259 Rhododendron species, and used likelihood and Bayesian statistics to analyze the data. We analyzed the markers separately to discuss and understand incongruence among the data sets and among previous studies. RESULTSWe found that the larger a subgenus, the more strongly it is supported as monophyletic. However, the smaller subgenera pose several problems, e.g., R. subgen. Azaleastrum consists of two sections inferred to be polyphyletic. The main shift to higher diversification in the genus occurred in the Himalayan/SE Asian clade of R. subgen. Hymenanthes. We found that polyploidy occurs in almost all subgenera but most polyploid species are within R. subgen. Rhododendron sections Rhododendron and Schistanthe. CONCLUSIONWhereas previous reports stated that genome sizes of tropical plants are lower than those of colder and temperate regions in angiosperms in general, our study provides evidence for such a shift to small genome-tropical species within a genus. Taken together, we see the merit in the recognition of the five major clades at the sub generic level but given the amount of incongruence a large amount of species cannot be confidently assigned to one of these five clades. Further, genome-wide data will be necessary to assess whether these currently unassignable taxa are independent taxa, assignable to one of the five major clades or whether they are inter-subgeneric hybrids.

plant biology↗