Biology subjects

Patel, N. A.

Publications and source records attributed to Patel, N. A..

5 recordsLinked to original sources

bioRxiv2026

LutABC of Veillonella parvula Deacidifies Streptococcus mutans Biofilms and Improves Biofilm Health

S. mutans and V. parvula cooperate in dental plaque to assemble a healthy biofilm and are associated with increased caries risk. S. mutans produces lactic acid from carbohydrates resulting in a final biofilm pH[~]4, while V. parvula metabolizes lactate to acetic and propionic acids resulting in pH[~]5. This process results in healthier biofilms that still generate a pH capable of demineralizing tooth surfaces (pH<5.5). The purpose of this study was to identify V. parvula genes required for deacidification of S. mutans biofilms and determine whether the ability of V. parvula to deacidify S. mutans biofilms correlates with enhanced biofilm health. Using transposon mutagenesis in V. parvula we identified several genes required for deacidification of S. mutans biofilms. These included numerous V. parvula transposon mutations in the previously unstudied lutABC lactate utilization operon. To assess biofilm health, S. mutans in the presence of various V. parvula mutants were stained with a LIVE/DEAD stain and imaged by fluorescence microscopy. An intact lutABC operon was required to enhance biofilm health, as demonstrated by plasmid-based complementation of a lutB transposon mutant. Transposon insertions in other loci unrelated to deacidification had no impact on biofilm health. Addition of HEPES buffer at the time of S. mutans biofilm assembly prevented full acidification of the biofilm and resulted in improved biofilm health, even without the addition of V. parvula. Finally, we found V. parvula can use either nitrate or fumarate as a final ETC electron acceptor during lactate utilization. In all, we found the lutABC lactate utilization operon of V. parvula is critical for the ability of V. parvula to deacidify S. mutans biofilms and promote biofilm health. Interfering with this pathway would interrupt the mutually beneficial relationship between S. mutans and V. parvula that leads to their co-association in caries, root caries, and early childhood caries.

microbiology↗

bioRxiv2023

Somatic mutation but not aneuploidy differentiates lung cancer in never-smokers and smokers.

Lung cancer in never-smokers disproportionately affects older women. To understand the mutational landscape of this cohort, we performed detailed genome characterization of 73 lung adenocarcinomas from participants of the Womens Health Initiative (WHI). We find enrichment of EGFR mutations in never-/light-smokers and KRAS mutations in heavy smokers as expected, but we also show that the specific variants of these genes differ by smoking status, with important therapeutic implications. Mutational signature analysis revealed signatures of clock, APOBEC, and DNA repair deficiency in never-/light-smokers; however, the mutational load of these signatures did not differ significantly from those found in smokers. Last, tumors from both smokers and never-/light-smokers shared copy number subtypes, with no significant differences in aneuploidy. Thus, the genomic landscape of lung cancer in never-/light-smokers and smokers is predominantly differentiated by somatic mutations and not copy number alterations.

genomics↗

bioRxiv2022

Data availability of open T-cell receptor repertoire data, a systematic assessment

The improvement of next-generation sequencing technologies has promoted the field of immunogenetics and produced numerous immunogenomics data. Modern data-driven research has the power to promote novel biomedical discoveries through secondary analysis of such data. Therefore, it is important to ensure data-driven research with great reproducibility and robustness for promoting a precise and accurate secondary analysis of the immunogenomics data. In scientific research, rigorous conduct in designing and conducting experiments is needed, specifically in scientific and articulate writing, reporting and interpreting results. It is also crucial to make raw data available, discoverable, and well described or annotated in order to promote future re-analysis of the data. In order to assess the data availability of published T cell receptor (TCR) repertoire data, we examined 11,918 TCR-Seq samples corresponding to 134 TCR-Seq studies ranging from 2006 to 2022. Among the 134 studies, only 38.1% had publicly available raw TCR-Seq data shared in public repositories. We also found a statistically significant association between the presence of data availability statements and the increase in raw data availability (p=0.014). Yet, 46.8% of studies with data availability statements failed to share the raw TCR-Seq data. There is a pressing need for the biomedical community to increase awareness of the importance of promoting raw data availability in scientific research and take immediate action to improve its raw data availability enabling cost-effective secondary analysis of existing immunogenomics data by the larger scientific community.

scientific communication and education↗

bioRxiv2019

Nutrient regulation of the islet epigenome controls adaptive insulin secretion

Adaptation of the islet {beta}-cell insulin secretory response to changing insulin demand is critical for blood glucose homeostasis, yet the mechanisms underlying this adaptation are unknown. Here, we show that nutrient-stimulated histone acetylation plays a key role in adapting insulin secretion through regulation of genes involved in {beta}-cell nutrient sensing and metabolism. Nutrient regulation of the epigenome occurs at sites occupied by the chromatin-modifying enzyme Lsd1 in islets. We demonstrate that {beta}-cell-specific deletion of Lsd1 leads to insulin hypersecretion, aberrant expression of nutrient response genes, and histone hyperacetylation. Islets from mice adapted to chronically increased insulin demand exhibited similar epigenetic and transcriptional changes. Moreover, genetic variants associated with fasting glucose and type 2 diabetes are enriched at LSD1-bound sites in human islets, suggesting that interpretation of nutrient signals is genetically determined. Our findings reveal that adaptive insulin secretion involves Lsd1-mediated coupling of nutrient state to regulation of the islet epigenome.

physiology↗

bioRxiv2019

LSD1-mediated enhancer silencing enables endocrine cell development through attenuation of retinoic acid signalling.

Developmental progression depends on temporally defined changes in gene expression mediated by transient exposure of lineage intermediates to signals in the progenitor niche. To identify a possible contribution of cell-intrinsic epigenetic mechanisms to signal-induced transcriptional responses, we manipulated the signalling environment and activity of the histone demethylase LSD1 during stepwise differentiation of gut tube intermediates into pancreatic endocrine cells. Analysis of enhancer and transcriptome landscapes revealed that lineage progression and endocrine cell differentiation requires LSD1-mediated silencing of transiently active retinoic acid (RA)-induced enhancers. In the absence of LSD1, early RA-responsive enhancers remain partially active despite RA removal, resulting in perduring expression of RA-induced genes, and failure to progress in development. Our findings identify LSD1-mediated enhancer silencing as a cell-intrinsic epigenetic feedback mechanism by which the duration of the transcriptional response to a developmental signal is limited. Given LSD1s requirement in numerous developmental contexts, the here-described mechanism would be broadly relevant.

developmental biology↗