Biology subjects

Goodney, G.

Publications and source records attributed to Goodney, G..

4 recordsLinked to original sources

bioRxiv2024

Changes in Proteome Profiles Linked to Hormonal Contraceptive Use Among African American Women with untreated high blood pressure

BackgroundHypertension is a leading contributor to cardiovascular disease in reproductive-age women, with African American women experiencing disproportionate risk and severity. Oral contraceptive (OC) use has been implicated in elevating blood pressure, but the underlying molecular mechanisms remain unclear. Understanding the proteomic alterations associated with OC use may provide novel insights into the biological pathways contributing to OC-related hypertensive risk. ObjectiveTo identify proteomic signatures associated with oral contraceptive use among premenopausal African American women with stage 2 hypertension and elucidate pathways that may contribute to blood pressure regulation in this population. Study DesignWe evaluated 2,941 serum proteins measured on the Olink platform to assess associations with oral contraception use in 51 pre-menopausal women with untreated stage 2 hypertension (13 OC users and 38 non-users). A generalized linear model was fitted for each protein, adjusting for age, body mass index, alcohol consumption, level of education, and physical activity. Pathway enrichment analysis was carried out to identify common pathways among the proteins associated with oral contraceptive use. Gene Ontology enrichment analysis was conducted to gain insight into the functional characteristics of the proteins and the underlying biology. ResultsWe identified 44 proteins significantly associated with OC use (FDR [≤] 0.05), including known and novel candidates. Among these, 13 proteins were elevated in OC users, including SERPINA6, SERPINA7, and TNFSF13, markers implicated in hormone transport, RAAS activation, and chronic inflammation. Proteins such as PLAU and PLAUR were enriched in sympathetic nervous system signaling and coagulation pathways, while SCG3 suggested neuroendocrine involvement. Enrichment analysis revealed overrepresentation of pathways related to complement and coagulation cascades, cholesterol metabolism, and the renin-angiotensin-aldosterone system.. ConclusionsOC use among premenopausal African American women, with stage 2 untreated hypertension, is associated with alterations in circulating proteins involved in neurohormonal signaling, immune modulation, lipid regulation, and vascular remodeling. The findings provide novel insights into the proteomic landscape associated with oral contraceptive in these women.

genomics↗

bioRxiv2024

Regulatory Roles of Long Non-Coding RNAs in Arterial Stiffness and Hypertension: Insights from Two African American Studies

BackgroundArterial stiffness, commonly assessed via pulse wave velocity (PWV), is marked by reduced arterial elasticity and serves as a significant risk factor for cardiovascular disease and an early indicator of hypertension. This study investigated the regulatory roles of long non-coding RNAs (lncRNAs) in modulating mRNAs associated with arterial stiffness and hypertension, with a particular focus on African Americans, a population disproportionately impacted by hypertension. MethodsWe utilized whole-blood transcriptome sequencing data from two African American (AA) cohorts with high hypertension prevalence: the GENE-FORECAST study (436 subjects) and the MH-GRID study (179 subjects). Our objectives were to: (1) identify lncRNAs and mRNAs differentially expressed (DE) between the upper and lower tertiles of PWV, (2) determine DE lncRNAs associated with the expression levels of each DE mRNA, and (3) link the lncRNA-modulated mRNAs to hypertension across both datasets. ResultsDifferential expression analysis revealed 1,035 DE mRNAs and 31 DE lncRNAs between upper and lower PWV groups. Then lncRNA-mRNA pairs significantly associated were identified, involving 31 unique lncRNAs and 1,034 unique mRNAs. Finally, 22 of the lncRNA-modulated mRNAs initially linked to PWV were found associated with hypertension, in both datasets. Interestingly, 30 lncRNAs were linked to the expression of UCP2 (Uncoupling Protein 2), a gene implicated in oxidative stress and endothelial function. ConclusionsOur findings underscore the significant roles of lncRNAs in regulating gene expression associated with arterial stiffness and hypertension. The differential expression of UCP2 in relation to PWV and hypertension, along with its potential regulation by lncRNAs, offers valuable insights into the molecular mechanisms underlying arterial stiffness and its connection with hypertension.

genomics↗

bioRxiv2024

Co-localized SNPs Affecting the Expression of Taste Perception Genes are linked to Alzheimer's Disease

BackgroundWhile previous research has shown the potential links between taste perception pathways and brain-related conditions, the area involving Alzheimers disease remains incompletely understood. Taste perception involves neurotransmitter signaling, including serotonin, glutamate, and dopamine. Disruptions in these pathways are implicated in neurodegenerative diseases. The integration of olfactory and taste signals in flavor perception may impact brain health, evident in olfactory dysfunction as an early symptom in neurodegenerative conditions. Shared immune response and inflammatory pathways may contribute to the association between altered taste perception and conditions like neurodegeneration, present in Alzheimers disease. MethodsThis study consists of an exploration of expression-quantitative trait loci (eQTL), utilizing whole-blood transcriptome profiles, of 28 taste perception genes, from a combined cohort of 475 African American subjects. This comprehensive dataset was subsequently intersected with single-nucleotide polymorphisms (SNPs) identified in Genome-Wide Association Studies (GWAS) of Alzheimers Disease (AD). Finally, the investigation delved into assessing the association between eQTLs reported in GWAS of AD and the profiles of 741 proteins from the Olink Neurological Panel. ResultsThe eQTL analysis unveiled 3,547 statistically significant SNP-Gene associations, involving 412 distinct SNPs that spanned all 28 taste genes. In 17 GWAS studies encompassing various traits, a total of 14 SNPs associated with 12 genes were identified, with three SNPs consistently linked to Alzheimers disease across four GWAS studies. All three SNPs demonstrated significant associations with the down-regulation of TAS2R41, and two of them were additionally associated with the down-regulation of TAS2R60. In the subsequent pQTL analysis, two of the SNPs linked to TAS2R41 and TAS2R60 genes (rs117771145 and rs10228407) were correlated with the upregulation of two proteins, namely EPHB6 and ADGRB3. ConclusionsOur investigation introduces a new perspective to the understanding of Alzheimers disease, emphasizing the significance of bitter taste receptor genes in its pathogenesis. These discoveries set the stage for subsequent research to delve into these receptors as promising avenues for both intervention and diagnosis. Nevertheless, the translation of these genetic insights into clinical practice requires a more profound understanding of the implicated pathways and their pertinence to the diseases progression across diverse populations.

genomics↗

bioRxiv2018

Microbial and Metabolic Succession on Common Building Materials Under High Humidity Conditions

Despite considerable efforts to characterize the ecology of bacteria and fungi in the built environment (BE), the metabolic mechanisms underpinning their colonization and successional dynamics remain unclear. Here, we applied bacterial/viral particle counting, qPCR, 16S and ITS rRNA amplicon sequencing, and metabolomics to longitudinally characterize the ecological dynamics of four commonly used building materials maintained at high humidity conditions (~94% RH). We varied the natural inoculum provided to each material by placing them in different occupied spaces, and we wet the surface of half of the samples of each material to simulate a flooding event. As expected, different materials showed different bacterial and viral particle abundance, with wet materials having higher growth rates and lower alpha diversity compared to non-wetted materials. Wetting described the majority of the variance in bacterial, fungal and metabolite structure, and material type only influenced bacterial and metabolic diversity, while location of inoculation was only weakly associated with bacterial and fungal beta diversity. Metabolites indicative of microbial activity were identified, as were those that were native to the surface material. Glucose-phosphate was abundant on all materials (except mold-free gypsum) and was correlated with Enterobacteriaceae, which could indicate a potential bacterial nutrient source. A compound consistent with scopoletin, a plant metabolite with antimicrobial activity, was significantly negatively correlated with Bacillus and positively correlated with Pseudomonas and enriched in medium density fiberboard (MDF) materials. In wet samples, the alkaloids nigragillin and fumigaclavine C, both with antimicrobial properties, were significantly positively correlated with the fungal phylum Ascomycota. Nigragillin, was also negatively correlated with Bacillus and Pseudomonas abundance. Thiabendazole and azoxystrobin (anti-fungal compounds) were highly abundant on mold-resistant gypsum wallboard and likely directly influenced the decreased fungal growth observed on this material. The mold-resistant gypsum material also showed a significant increase in bacterial alpha diversity, and bacterial and viral particle abundance, as well as a decrease in metabolite diversity, likely a result of reduced fungal growth. Penicillium taxa were positively correlated with thiabendazole, which suggested the persistence of resistant strains. Also, specific to the wet samples, Bacillus abundance was positively correlated with the azoxystrobin, suggesting bi-directional competitive adaptation, and positively correlated with metabolites known to interfere with Pseudomonas biofilm formation, which could explain the anti-correlation between these taxa. As expected, high moisture conditions enabled faster growth of inoculating microorganisms, whose composition, chemistry, and competition was shaped by surface material, suggesting that both fungal and bacterial growth need to be considered when determining the impact of dampness in built environments.

microbiology↗