Biology subjects

Dubey, P.

Publications and source records attributed to Dubey, P..

21 records · Page 2Linked to original sources

bioRxiv2019

Bordetella Colonization Factor A (BcfA) elicits protective immunity against Bordetella bronchiseptica in the absence of an additional adjuvant

Bordetella bronchiseptica (B. bronchiseptica) is an etiologic agent of respiratory diseases in animals and humans. Despite widespread use of veterinary B. bronchiseptica vaccines, there is limited information on their composition, relative efficacy, and the immune responses they elicit. Furthermore, human B. bronchiseptica vaccines are not available. We leveraged the dual antigenic and adjuvant functions of BcfA to develop acellular B. bronchiseptica vaccines in the absence of an additional adjuvant. Balb/c mice immunized with BcfA alone or a trivalent vaccine containing BcfA and the Bordetella antigens FHA and Prn were equally protected against challenge with a prototype B. bronchiseptica strain. The trivalent vaccine protected mice significantly better than the canine vaccine Bronchicine(R) and provided protection against a B. bronchiseptica strain isolated from a dog with kennel cough. Th1/17-polarized immune responses correlate with long-lasting protection against Bordetellae and other respiratory pathogens. Notably, BcfA strongly attenuated the Th2 responses elicited by FHA/Prn, resulting in Th1/17-skewed responses in inherently Th2-skewed Balb/c mice. Thus, BcfA functions as both an antigen and an adjuvant, providing protection as a single component vaccine. BcfA-adjuvanted vaccines may improve the efficacy and durability of vaccines against Bordetellae and other pathogens.

immunology↗

bioRxiv2018

Atypical septate junctions maintain the somatic enclosure around maturing spermatids and prevent premature sperm release in Drosophila testis.

Tight junctions prevent the paracellular flow and maintain cell polarity in an epithelium. These are also essential for maintaining the blood-testis-barrier involved in regulating sperm differentiation. Septate junctions are orthologous to the tight junctions in insects. In Drosophila testis, major septate junction components co-localize at the interface of germline and somatic cells initially and then condense between the two somatic cells in a cyst after germline meiosis. Their localization is extensively remodeled in subsequent stages. We find that characteristic septate junctions are formed between the somatic cyst cells at the elongated spermatid stage. Consistent with the previous reports, knockdown of essential junctional components, Discs-large-1 and Neurexin-IV, in the somatic cyst cells, during the early stages, disrupted sperm differentiation beyond the spermatocyte stage. Somatic knockdown of these proteins during the final stages of spermatid maturation caused premature release of spermatids inside the testes, resulting in partial loss of male fertility. These results indicate the importance of maintaining mechanical integrity of the somatic enclosure during spermatid coiling and release in Drosophila testis. It also highlights the functional similarity with the tight junction proteins during spermatogenesis in mammalian testes.\n\nSummary statementDubey et al., showed that septate junctions stitch the somatic enclosure around maturing spermatids in Drosophila testis. Maintaining the integrity of this junction is essential for proper release of spermatids.

cell biology↗

bioRxiv2017

Processive movement of actin by biased polymerization: a new paradigm of axonal transport

Classic pulse-chase studies have shown that actin is conveyed in slow axonal transport, but the mechanistic basis for this movement is unknown. Recently, we reported that axonal actin was surprisingly dynamic, with focal assembly/dis-assembly events (\"hotspots\") and elongating polymers along the axon-shaft (\"trails\"). Using a combination of live imaging, super-resolution microscopy, and modeling, here we explore how these axonal actin dynamics can lead to processive transport. We found abundant actin nucleation, along with a slow, anterogradely-biased flow of actin in axon-shafts. Starting with first principles of monomer/filament assembly - and incorporating imaging data - we generated a quantitative model simulating axonal hotspots and trails. Our simulations predict that the axonal actin dynamics indeed lead to an anterogradely-biased flow of the population, at rates consistent with slow transport. Collectively, the data point to a surprising scenario where local assembly and biased polymerization generate the slow axonal transport of actin. This mechanism is distinct from polymer-sliding, and seems well suited to convey highly dynamic cytoskeletal cargoes.\n\nAcknowledgementsThis work was supported by an NIH grant to SR (R01NS075233). The authors thank Stephanie Gupton (UNC) for the Mena/Vasp constructs.

neuroscience↗