Publications by authors named "Nancy D Denslow"

Background/objectives: Chronic kidney disease of unknown etiology (CKDu) disproportionately affects young male agricultural workers who are otherwise healthy. There is a scarcity of biomarkers for early detection of this type of kidney disease. We hypothesized that small extracellular vesicles (sEVs) released into urine may provide novel biomarkers.

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Background: The coronavirus disease 2019 (COVID-19) is a viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and associated with systemic inflammation. Inflammation is an important process that follows infection and facilitates the body's innate immune response and repair of damaged tissue. Polyunsaturated fatty acids play an important role in the inflammatory process.

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Drinking water treatment residuals (DWTRs) produced as a result of the coagulation-flocculation process during water treatment are considered waste materials. Characterization of this material shows its ability to sequester metals and other anionic and cationic chemicals. Drinking water treatment residuals from two different drinking water treatment plants located in Wyoming and Oregon were evaluated for their ability to function as viable capping materials of metal-contaminated sediments.

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Introduction: Recombinant alpha-1 antitrypsin (AAT) therapy has been shown to have beneficial effects to mitigate the progression of various diseases. Here, we hypothesized that administration of pharmaceutical-grade human AAT (hAAT) is effective in mitigating hypertension induced by salt-loading in juvenile mice by reducing the concentration of diacylglycerols (DAGs) and activity of protein kinase C (PKC) in the kidney.

Methods: Four-week old 129Sv mice were salt-loaded to induce hypertension and then administered hAAT or vehicle.

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The importance of steroidogenesis is underscored by its vital and conserved functions from higher to lower vertebrate species, such as stress, immune and inflammatory responses, sexual development and reproduction, osmoregulation and even the ability to adapt to the environment and environmental changes. Correspondingly, the rate-limiting step of steroidogenesis mediated by the steroidogenic acute regulatory protein is an ongoing target for scientific investigation. An expanding collection of studies has now reported key similarities, as well as some differences, in the transcriptional and translational regulation of steroidogenic acute regulatory protein across species.

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While the production of a draft genome has become more accessible due to long-read sequencing, the annotation of these new genomes has not been developed at the same pace. Long-read RNA sequencing offers a promising solution for enhancing gene annotation. In this study, we explore how sequencing platforms, Oxford Nanopore R9.

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Exposure to contaminants, such as the herbicide glyphosate, can suppress protective immune functions. Glyphosate is the herbicide most used worldwide and has been found in the plasma of more than 50 % of the Florida manatees (Trichechus manatus latirostris) and all-year-round in their aquatic environment. Our objectives were to analyze the consequences of glyphosate exposure on their immune responses via T-lymphocyte proliferation assays and transcriptomics.

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This study evaluated drinking water treatment residuals (DWTR) as an in-situ capping material for metal-contaminated sediments using Gust-chamber experiments. Metal release from non-capped and DWTR-capped sediments was measured under increasing shear stress (τ) from 0.05 to 0.

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Though phased out from use in the United States, environmental contamination by organochlorine pesticides (OCPs) remains a widespread issue, especially around intensive agricultural regions. OCPs, such as dichlorodiphenyltrichloroethane (DDT) and its primary metabolite, dichlorodiphenyldichloroethylene (DDE), have been detected in soils, sediments, surface waters, and biota decades after their discontinued use. As OCPs are persistent and can bioaccumulate in fats, these compounds can transfer and magnify across food webs.

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Article Synopsis
  • * They generated over 427 million long-read sequences and found that longer, more accurate sequences yield better transcript detection, while increased read depth enhances quantification.
  • * The study suggests that using reference-based tools works best for well-annotated genomes and recommends incorporating extra data to better identify rare transcripts, providing a benchmark for improving transcriptome analysis techniques in the future.
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  • Cathepsin B (CtsB) is a protease linked to various health conditions and its absence in mice was examined to understand diabetic kidney disease induced by streptozotocin (STZ).
  • Analysis of urinary extracellular vesicles (uEVs) revealed specific bioactive lipids associated with oxidative stress and renal cell death in CtsB knockout mice treated with STZ.
  • Findings indicate that STZ treatment activates antioxidant responses in the kidneys but primarily leads to apoptosis (programmed cell death) rather than ferroptosis, highlighting key mechanisms in diabetic kidney disease development.
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Florida manatees (Trichechus manatus latirostris) are protected as a threatened species, and data are lacking regarding their reproductive physiology. This study aimed to (1) quantify plasma steroid hormones in Florida manatees from two field sites, Crystal River and Indian River Lagoon, at different gestational stages and to (2) identify individual lipids associated with pregnancy status. Ultra-high performance liquid chromatography-tandem mass spectrometric analysis was used to measure plasma steroid hormones and lipids.

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Drinking water treatment residuals (DWTRs) are produced from the coagulation and flocculation processes in conventional drinking water treatment. The abundant metal oxide content of these materials resulting from the use of coagulants, like alum and ferric chloride, has driven strong research interest into the reuse of DWTRs as sorptive materials. Using a suite of aluminum-based DWTRs, we provide new insights into Hg(II) sorption mechanisms.

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Article Synopsis
  • Extracellular Vesicles (EVs) are tiny vesicles from various cell types that play a key role in communication and signaling between cells.
  • The study aimed to see if EVs from the bronchoalveolar-lavage fluid (BALF) of pediatric cystic fibrosis (CF) and asthma patients could enhance epithelial sodium channel (ENaC) activity in normal human airway cells, focusing on specific lipids in EVs.
  • Results showed that both CF and asthma EVs have distinct lipid profiles, but both types significantly increased ENaC activity in airway cells compared to control EVs.
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Article Synopsis
  • The Long-read RNA-Seq Genome Annotation Assessment Project (LRGASP) Consortium aimed to evaluate long-read sequencing for analyzing transcripts by generating over 427 million sequences from various species.
  • The findings highlighted that longer, accurate sequences yield better transcript identification, while increased read depth enhances quantification accuracy, particularly in well-annotated genomes.
  • The study serves as a benchmark for transcriptome analysis strategies and suggests using additional data for detecting rare transcripts or employing reference-free methods.
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The Yucatan coastal zone is an area that contributes to many anthropogenic activities resulting in substantial contamination (metals, pesticides) in aquatic organisms. The dolphin is an excellent sentinel animal used in studying contamination in this area. Some substances found in dolphins have been identified as toxic causing alterations in the properties of membranes and produce lipid peroxidation especially heavy metals.

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Cathpesin B is a multi-functional protease that plays numerous roles in physiology and pathophysiology. We hypothesized that actin cytoskeleton proteins that are substrates of cathepsin B, various lipids, and kinases that are regulated by lipids would be down-regulated in the kidney of cathepsin B knockout mice. Here, we show by Western blot and densitometric analysis that the expression and proteolysis of the actin cytoskeleton proteins myristoylated alanine-rich C-kinase substrate (MARCKS) and spectrin are significantly reduced in kidney cortex membrane fractions of cathepsin B knockout mice compared to C57B6 wild-type control mice.

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Florida manatees (Trichechus manatus latirostris), a federally protected species, are classified as threatened due to anthropogenic stressors. Manatees inhabit sites that are impacted by human activities that can negatively affect stress physiology and metabolism. Samples collected from healthy manatees (pregnant females, non-pregnant females, and males) at Crystal River and Indian River Lagoon in Florida, were assessed for adrenal hormones, proteins, glucose, and lipid content in plasma.

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  • Dapagliflozin, an SGLT2 inhibitor, may help manage various complications of type 2 diabetes by promoting glucose excretion and possibly altering kidney cell lipid composition.
  • A study using diabetic mice showed that dapagliflozin treatment changed the types and concentrations of membrane lipids in the kidney, with notable increases in certain phosphatidylethanolamines.
  • The research also indicated reduced extracellular vesicle release and changes in lipid raft protein distribution, suggesting that dapagliflozin could influence lipid-related signaling pathways in the diabetic kidney.
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Hypertension may develop before or after the onset of diabetes and it is known to increase the risk of developing diabetic nephropathy. Alpha-1 antitrypsin (AAT) is a multi-functional protein with beneficial effects in various diseases but its role in reducing blood pressure in the diabetic kidney has not been thoroughly studied. Like blood pressure, epithelial sodium channels (ENaC) and its adaptor protein myristoylated alanine-rich C-kinase substrate (MARCKS) are regulated by circadian rhythms.

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Ferroptosis is a druggable, iron-dependent form of cell death that is characterized by lipid peroxidation but has received little attention in lupus nephritis. Kidneys of lupus nephritis patients and mice showed increased lipid peroxidation mainly in the tubular segments and an increase in Acyl-CoA synthetase long-chain family member 4, a pro-ferroptosis enzyme. Nephritic mice had an attenuated expression of SLC7A11, a cystine importer, an impaired glutathione synthesis pathway, and low expression of glutathione peroxidase 4, a ferroptosis inhibitor.

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Article Synopsis
  • * The research investigated the lipid profiles of urinary EVs from aged mice in both inactive and active phases and found differences, particularly an increase in specific lipids in active phase EVs.
  • * An ENaC inhibitor reduced blood pressure in aged male mice, and active-phase uEVs enhanced specific cellular responses indicating a relationship between lipid raft organization and blood pressure regulation in aging.
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The C-type natriuretic peptide receptor (NPRC) is expressed in many cell types and binds all natriuretic peptides with high affinity. Ligand binding results in the activation or inhibition of various intracellular signaling pathways. Although NPRC ligand binding has been shown to regulate various ion channels, the regulation of endothelial sodium channel (EnNaC) activity by NPRC activation has not been studied.

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  • * Brevetoxins affect the immune system by activating immune cells and altering the production of various immune factors, leading to potential health implications for marine animals.
  • * The review highlights gaps in current research on the long-term effects of brevetoxin exposure and proposes pathways for understanding its immunotoxicity, aiming to assist researchers and policymakers in addressing the risks associated with algal blooms.
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  • The study evaluates the toxicity of a new type of dispersant made from silicon dioxide nanoparticles (NPs) that are modified with specific chemical compounds to improve their effectiveness.
  • This new dispersant, called NP-PCL-POEGMA, is compared to a previously evaluated dispersant (NP-HPG) to observe improvements in protecting fish embryos from crude oil toxicity.
  • Findings show that the NP-PCL-POEGMA samples were non-toxic to embryos and provided better protection against harmful effects than the previous dispersant, suggesting potential for safer alternatives to commercial products like Corexit.
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