Biology subjects

Nayak, U.

Publications and source records attributed to Nayak, U..

6 recordsLinked to original sources

bioRxiv2025

Cfap300 regulates the transdifferentiation of Corpuscle of Stannius cells in zebrafish

Stanniocalcin 1 (Stc1) is a hormone secreted by the Corpuscle of Stannius (CS) gland in teleost fish, including zebrafish, where it regulates calcium homeostasis. The CS gland forms by transdifferentiation of pronephric tubule epithelial cells at the distal early (DE) and distal late (DL) boundary. Although transdifferentiation is known in development and disease, the underlying mechanisms remain unclear. Here, we show that cfap300, a DNAAF implicated in primary ciliary dyskinesia (PCD), is essential for CS gland formation. TALEN-generated cfap300 mutants develop normally and show no nephron segmentation defects, but exhibit impaired CS development, which could be partially rescued by cfap300 mRNA injection. Further, cfap300 mutants display increased expression of cdh17 driven by Hnf1ba, which blocks CS precursor transdifferentiation. Knockdown of cdh17 or hnf1ba restores CS formation. These results uncover a Cfap300-Hnf1ba-Cdh17 pathway that regulates epithelial-to-endocrine transdifferentiation, revealing a novel, lineage-specific role for a DNAAF protein in endocrine organogenesis.

developmental biology↗

bioRxiv2025

Chikungunya virus susceptibility increases in the absence of mk2b and mk3 genes in zebrafish model

Chikungunya virus (CHIKV) infection imposes a significant socio-economic burden due to the absence of effective antiviral treatments and vaccines. Host factors are essential for the CHIKV life cycle, making them promising targets for antiviral therapy. Previous studies have identified Mitogen-activated protein kinase activated protein kinase 2 (MK2) and Mitogen-activated protein kinase activated protein kinase 3 (MK3) as key host factors in CHIKV infection; however, their role in an animal model remain unclear. This study highlights the critical roles of MK2 and MK3 host factors in an animal model following CHIKV infection. To investigate their functions, mk2b (mk2b-/-), mk3 (mk3-/-), and mk2b-mk3 (mk2b-/-mk3-/-) double knockout zebrafish were generated using the CRISPR-Cas9 technique. A significant high viral titer of CHIKV was observed in case of all knockout groups compared to the wild-type (WT) control using plaque assay, RT-qPCR and immunofluorescence assay. Among the knockout groups, mk3-/- displayed the highest susceptibility to CHIKV, followed by mk2b-/-. In contrast, the mk2b-/-mk3-/- double knockout exhibited the lowest susceptibility to CHIKV infection. Additionally, severe symptoms such as bent body, impaired response to physical stimuli, and increased mortality were most pronounced in mk3-/- larvae compared to other knockouts and the WT. The expression levels of inf{phi}1 and rsad2 were also elevated in all knockout groups during the early days of infection indicating higher interferon response in the absence of mk2b and mk3 during CHIKV infection. In conclusion, this study confirms that the mk2b and mk3 host proteins are essential in controlling the CHIKV infection in organism level and subsequently may contribute in designing antiviral therapeutics in future. Furthermore, the knockout model of mk2b and mk3 in zebrafish could serve as a valuable tool for studying their roles in other viral infections. Author SummaryCHIKV, transmitted by Aedes aegypti and Aedes albopictus mosquitoes, causes febrile illness and has spread across Africa, Asia, Europe, and America. Despite extensive research, effective antiviral drugs and vaccines are yet to be commercially available. This study examines the role of mk2b and mk3 host factors following CHIKV infection. For this purpose, mk2b and mk3 single as well as double knockout have been generated in zebrafish using the CRISPR-Cas-9 technique. Findings suggest that zebrafish exhibit high CHIKV susceptibility in the absence of mk2b and mk3, confirming its importance during infection. Moreover, these three knockout models could serve as a valuable platform for examine the role of mk2b and mk3 in the presence of other viral infection.

molecular biology↗

bioRxiv2023

Leveraging type 1 diabetes human genetic and genomic data in the T1D Knowledge Portal

Translating genetic discoveries for type 1 diabetes (T1D) into mechanistic insight can reveal novel biology and therapeutic targets but remains a major challenge. We developed the T1D Knowledge Portal (T1DKP), a disease-specific resource of genetic and functional annotation data that enables users to develop hypotheses for T1D-based research and target discovery. The T1DKP can be used to query genes and genomic regions for genetic associations, identify epigenomic features, access results of bioinformatic analyses, and obtain expert-curated resources. The T1DKP is available at http://t1d.hugeamp.org.

genetics↗

bioRxiv2021

Nonsterile immunity to cryptosporidiosis in infants is associated with mucosal IgA against the sporozoite and protection from malnutrition

We conducted a longitudinal study of cryptosporidiosis from birth to three years of age in an urban slum of Dhaka Bangladesh. Fecal DNA was extracted from monthly surveillance samples and diarrheal stool samples collected from 392 infants from birth to three years. A pan-Cryptosporidium qPCR assay was used to identify sub-clinical and symptomatic cryptosporidiosis. Anthropometric measurements were collected quarterly to assess child nutritional status. 31% (121/392) of children experienced a single and 57% (222/392) multiple infections with Cryptosporidium. Repeat infections had a lower burden of parasites in the stool (Cq slope = -1.85; p<0.0001) and were more likely to be sub-clinical (Chi square test for trend; p=0.01). Repeat infections were associated with the development of growth faltering (Pearson correlation = -0.18; p=0.0004). High levels of fecal IgA antibodies against the Cryptosporidium Cp23 sporozoite protein at one year of life were associated with a delay in reinfection and amelioration of growth faltering through three years of life (HAZ IgA high responders -1.323 {+/-} 0.932 versus HAZ -1.731 {+/-} 0.984 p=0.0001). We concluded that nonsterile immunity to cryptosporidiosis in young children was associated with high levels of mucosal IgA anti-Cp23 and protection from diarrhea and growth faltering. Authors SummaryCryptosporidium is one of the top causes of diarrhea and growth faltering in Bangladesh infants. We discovered that a prior infection resulted in incomplete immunity that protected from diarrhea and growth faltering but not infection and was associated with mucosal IgA against a sporozoite surface protein Cp23. The most important implication of these findings is that a cryptosporidiosis vaccine may not need to achieve complete protection from infection to have a beneficial impact on child health.

microbiology↗

bioRxiv2020

Genetic Landscape of Gullah African Americans

ObjectivesGullah African Americans are descendants of formerly enslaved Africans living in the Sea Islands along the coast of the southeastern U.S., from North Carolina to Florida. Their relatively high numbers and geographic isolation were conducive to the development and preservation of a unique culture that retains deep African features. Although historical evidence supports a West and Central African ancestry for the Gullah, linguistic and cultural evidence of a connection to Sierra Leone has led to the suggestion of this country/region as their ancestral home. This study sought to elucidate the genetic structure and ancestry of the Gullah. Materials and MethodsWe leveraged whole-genome genotype data from Gullah, African Americans from Jackson, Mississippi, Sierra Leone Africans, and population reference panels from Africa and Europe, to infer population structure, ancestry proportions, and global estimates of admixture. ResultsRelative to southeastern non-Gullah African Americans, the Gullah exhibit higher mean African ancestry, lower European admixture, a similarly small Native American contribution, and stronger male-biased European admixture. A slightly tighter bottleneck in the Gullah 13 generations ago suggests a largely shared demographic history with non-Gullah African Americans. Despite a slightly higher relatedness to Sierra Leone, our data demonstrate that the Gullah are genetically related to many West African populations. DiscussionThis study confirms that subtle differences in African American population structure exist at finer regional levels. Such observations can help to inform medical genetics research in African Americans, and guide the interpretation of genetic data used by African Americans seeking to explore ancestral identities. Research HighlightsO_LIUsing genomic data, we show that the Gullah have lower European and higher West African genomic background compared to non-Gullah African Americans, confirming their diverse African ancestry and rejecting a model that asserts a predominant Sierra Leone origin. C_LIO_LIOur data reveal a largely shared demographic history with southeastern non-Gullah African Americans, but also subtle differences related to high African genetic ancestry due to isolation in the Sea Islands. C_LI

genetics↗

bioRxiv2020

Megasphaera in the stool microbiota is negatively associated with diarrheal cryptosporidiosis

BackgroundThe protozoan parasites in the Cryptosporidium genus cause both acute diarrheal disease and subclinical (i.e. non-diarrheal) disease. It is unclear if the microbiota can influence the manifestation of diarrhea during a Cryptosporidium infection. MethodsTo characterize the role of the gut microbiota in diarrheal cryptosporidiosis, the microbiome composition of both diarrheal and surveillance Cryptosporidium-positive fecal samples was evaluated using 16S rRNA gene sequencing. Additionally, the microbiome composition prior to infection was examined to test whether a preexisting microbiome profile could influence the Cryptosporidium infection phenotype. ResultsFecal microbiome composition was associated with diarrheal symptoms at two timepoints. Megasphaera was significantly less abundant in diarrheal samples when compared to subclinical samples at the time of Cryptosporidium detection (log2(fold change) = -4.3, p=10-10) and prior to infection (log2(fold change) = -2.0, p=10-4). Random forest classification also identified Megasphaera abundance in the pre- and post-exposure microbiota.as predictive of a subclinical infection. ConclusionsMicrobiome composition broadly, and specifically low Megasphaera abundance, was associated with diarrheal symptoms prior to and at the time of Cryptosporidium detection. This observation suggests that the gut microenvironment may play a role in determining the severity of a Cryptosporidium infection. SummaryMegasphaera abundance in the stool of Bangladeshi infants is associated with the development of diarrhea upon infection with the Cryptosporidium parasite.

microbiology↗