Publications by authors named "KYLE J"

Senescence is a non-proliferative, survival state that cancer cells can enter to escape therapy. In addition to soluble factors, senescence cells secrete extracellular vesicles (EVs), which are important mediators of intercellular communication. To explore the role of senescent cell-derived EVs (senEVs) in inflammatory responses to senescence, we developed an engraftment-based senescence model in wild-type mice and genetically blocked senEV release in vivo, without significantly affecting soluble mediators.

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Background: The rumen fluke, Calicophoron daubneyi, is the major paramphistome species infecting ruminants within Europe. Adult flukes reside within the rumen where they are in direct contact with a unique collection of microorganisms. Here, we report a 1.

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Vertebrates differ over 100,000-fold in responses to pro-inflammatory agonists such as bacterial lipopolysaccharide (LPS), complicating use of animal models to study human sepsis or inflammatory disorders. We compared transcriptomes of resting and LPS-exposed blood from six LPS-sensitive species (rabbit, pig, sheep, cow, chimpanzee, human) and four LPS-resilient species (mice, rats, baboon, rhesus), as well as plasma proteomes and lipidomes. Unexpectedly, at baseline, sensitive species already had enhanced expression of LPS-responsive genes relative to resilient species.

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Introduction: The placenta uses lipids and other nutrients to support its own metabolism hence impacting the type and amount of these substrates available to the growing fetus. Maternal obesity and gestational diabetes (GDM) can disrupt placental lipid metabolism and thus lead to altered fetal growth contributing to adverse pregnancy outcomes and developmentally programing the offspring for disease in later life. Understanding obesity and GDM driven changes in placental lipid metabolism is thus important.

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Introduction: Human metabolomics has made significant strides in understanding metabolic changes and their implications for human health, with promising applications in diagnostics and treatment, particularly regarding the gut microbiome. However, progress is hampered by issues with data comparability and reproducibility across studies, limiting the translation of these discoveries into practical applications.

Objectives: This study aims to evaluate the fit-for-purpose of a suite of human stool samples as potential candidate reference materials (RMs) and assess the state of the field regarding harmonizing gut metabolomics measurements.

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Introduction: Obesity and gestational diabetes (GDM) are associated with adverse pregnancy outcomes and program the offspring for cardiometabolic disease in a sexually dimorphic manner. The placenta transfers lipids to the fetus and uses these substrates to support its own metabolism impacting the amount of substrate available to the growing fetus.

Methods: We collected maternal plasma and placental villous tissue following elective cesarean section at term from women who were lean (pre-pregnancy BMI 18.

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Article Synopsis
  • Understanding fungal lipid biology is essential for discovering new antifungal targets because lipids are crucial for cellular functions.
  • The localization of double bonds in lipid structures greatly influences their functionality, and this can be accurately identified using specialized techniques like ozone-induced dissociation mass spectrometry (OzID-MS).
  • Our study implemented OzID-MS and LipidOz software to analyze lipid profiles in genetically modified yeast strains, improving data processing efficiency by retraining a deep learning model to focus on promising targets while reducing the time needed for analysis.
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  • * There's a gap in automated quality control tools for metabolomics, as most existing tools focus on proteomics.
  • * PeakQC is a new software developed for automated quality control of mass spectrometry data, functioning across various omics types and instruments, enhancing the quality and reliability of analyses.
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Understanding of how soil organic matter (SOM) chemistry is altered in a changing climate has advanced considerably; however, most SOM components remain unidentified, impeding the ability to characterize a major fraction of organic matter and predict what types of molecules, and from which sources, will persist in soil. We present a novel approach to better characterize SOM extracts by integrating information from three types of analyses, and we deploy this method to characterize decaying root-detritus soil microcosms subjected to either drought or normal conditions. To observe broad differences in composition, we employed direct infusion Fourier-transform ion cyclotron resonance mass spectrometry (DI-FT-ICR MS).

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  • Despite extensive research on genomic changes in glioblastoma, the survival rate remains under 5% after five years.
  • This study aims to broaden the understanding of high-grade glioma by combining various biological analyses (proteomics, metabolomics, etc.) to identify complex regulatory mechanisms involved in tumor growth and progression.
  • Results from analysis of 228 tumors indicate significant variability in early-stage changes, but they converge on common outcomes affecting protein interactions and modifications, highlighting PTPN11's crucial role in high-grade gliomas.
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Background: Plant-based diets are not inherently healthy. Similar to omnivorous diets, they may contain excessive amounts of sugar, sodium, and saturated fats, or lack diversity. Moreover, vegans might be at risk of inadequate intake of certain vitamins and minerals commonly found in foods that they avoid.

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Human infections caused by viral pathogens trigger a complex gamut of host responses that limit disease, resolve infection, generate immunity, and contribute to severe disease or death. Here, we present experimental methods and multi-omics data capture approaches representing the global host response to infection generated from 45 individual experiments involving human viruses from the Orthomyxoviridae, Filoviridae, Flaviviridae, and Coronaviridae families. Analogous experimental designs were implemented across human or mouse host model systems, longitudinal samples were collected over defined time courses, and global multi-omics data (transcriptomics, proteomics, metabolomics, and lipidomics) were acquired by microarray, RNA sequencing, or mass spectrometry analyses.

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Viruses impact microbial systems through killing hosts, horizontal gene transfer, and altering cellular metabolism, consequently impacting nutrient cycles. A virus-infected cell, a "virocell," is distinct from its uninfected sister cell as the virus commandeers cellular machinery to produce viruses rather than replicate cells. Problematically, virocell responses to the nutrient-limited conditions that abound in nature are poorly understood.

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Background: Lipids are regulators of insulitis and β-cell death in type 1 diabetes development, but the underlying mechanisms are poorly understood. Here, we investigated how the islet lipid composition and downstream signaling regulate β-cell death.

Methods: We performed lipidomics using three models of insulitis: human islets and EndoC-βH1 β cells treated with the pro-inflammatory cytokines interlukine-1β and interferon-γ, and islets from pre-diabetic non-obese mice.

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Article Synopsis
  • The leaf-cutter ant ecosystem, specifically focusing on Atta cephalotes, serves as an effective model for understanding plant biomass breakdown, primarily facilitated by a symbiotic fungus called Leucoagaricus gongylophorus.
  • Researchers utilized advanced imaging techniques on thin sections of fungal gardens to study the degradation of lignin, a complex organic polymer, which is crucial in plant structure.
  • By mapping metabolites and proteins together, they discovered distinct microhabitats related to lignin breakdown, highlighting the fungi's important role in decomposing plant materials and revealing insights into the metabolic processes involved.
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Alzheimer's disease (AD) is a neurodegenerative disease with a complex etiology influenced by confounding factors such as genetic polymorphisms, age, sex, and race. Traditionally, AD research has not prioritized these influences, resulting in dramatically skewed cohorts such as three times the number of Apolipoprotein E (APOE) ε4-allele carriers in AD relative to healthy cohorts. Thus, the resulting molecular changes in AD have previously been complicated by the influence of apolipoprotein E disparities.

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Epithelial ovarian cancer (EOC) is the most common form of ovarian cancer. The poor prognosis generally associated with this disease has led to the search for improved therapies such as ferroptosis-inducing agents. Ferroptosis is a form of regulated cell death that is dependent on iron and is characterized by lipid peroxidation.

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Vertebrates differ greatly in responses to pro-inflammatory agonists such as bacterial lipopolysaccharide (LPS), complicating use of animal models to study human sepsis or inflammatory disorders. We compared transcriptomes of resting and LPS-exposed blood from six LPS-sensitive species (rabbit, pig, sheep, cow, chimpanzee, human) and four LPS-resilient species (mice, rats, baboon, rhesus), as well as plasma proteomes and lipidomes. Unexpectedly, at baseline, sensitive species already had enhanced expression of LPS-responsive genes relative to resilient species.

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Climate change is globally affecting rainfall patterns, necessitating the improvement of drought tolerance in crops. is a relatively drought-tolerant cereal. Functional stay-green sorghum genotypes can maintain green leaf area and efficient grain filling during terminal post-flowering water deprivation, a period of ~10 weeks.

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Importance: Although durable medical equipment and supplies (DMES) are commonly used to optimize the health and function in pediatric patients, little is known about the prevalence of use and spending on DMES.

Objective: To categorize the Healthcare Common Procedure Coding System (HCPCS) for distinguishing DMES types, and to measure the prevalence and related spending of DMES in pediatric patients using Medicaid.

Design, Setting, And Participants: This study is a cross-sectional analysis of the 2018 Merative Medicaid Database and included 4 569 473 pediatric patients aged 0 to 21 years enrolled in Medicaid in 12 US states from January 1 to December 31, 2018.

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Background: Physiological and biochemical processes across tissues of the body are regulated in response to the high demands of intense physical activity in several occupations, such as firefighting, law enforcement, military, and sports. A better understanding of such processes can ultimately help improve human performance and prevent illnesses in the work environment.

Methods: To study regulatory processes in intense physical activity simulating real-life conditions, we performed a multi-omics analysis of three biofluids (blood plasma, urine, and saliva) collected from 11 wildland firefighters before and after a 45 min, intense exercise regimen.

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The high prevalence of human papillomavirus (HPV) infection in China suggests there would be a substantial positive health impact of widespread vaccination against HPV. We adapted a previously described dynamic transmission model of the natural history of HPV infection and related diseases to the Chinese setting to estimate the public health impact in China of 2-valent (with and without cross-protection), 4-valent, and 9-valent HPV vaccination strategies. The model predicted the incidence and mortality associated with HPV-related diseases, including cervical and noncervical cancers, genital warts, and recurrent respiratory papillomatosis (RRP), based on the various vaccination coverage rate (VCR) scenarios, over a 100-year time horizon.

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Lipoproteins in cerebrospinal fluid (CSF) of the central nervous system (CNS) resemble plasma high-density lipoproteins (HDLs), which are a compositionally and structurally diverse spectrum of nanoparticles with pleiotropic functionality. Whether CSF lipoproteins (CSF-Lps) exhibit similar heterogeneity is poorly understood because they are present at 100-fold lower concentrations than plasma HDL. To investigate the diversity of CSF-Lps, we developed a sensitive fluorescent technology to characterize lipoprotein subspecies in small volumes of human CSF.

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