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result(s) for
"Carson, Meredith S."
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The obesity-breast cancer link: a multidisciplinary perspective
by
Devericks, Emily N
,
McCullough, Lauren E
,
Carson, Meredith S
in
Adipose tissue
,
Body fat
,
Breast cancer
2022
Obesity, exceptionally prevalent in the USA, promotes the incidence and progression of numerous cancer types including breast cancer. Complex, interacting metabolic and immune dysregulation marks the development of both breast cancer and obesity. Obesity promotes chronic low-grade inflammation, particularly in white adipose tissue, which drives immune dysfunction marked by increased pro-inflammatory cytokine production, alternative macrophage activation, and reduced T cell function. Breast tissue is predominantly composed of white adipose, and developing breast cancer readily and directly interacts with cells and signals from adipose remodeled by obesity. This review discusses the biological mechanisms through which obesity promotes breast cancer, the role of obesity in breast cancer health disparities, and dietary interventions to mitigate the adverse effects of obesity on breast cancer. We detail the intersection of obesity and breast cancer, with an emphasis on the shared and unique patterns of immune dysregulation in these disease processes. We have highlighted key areas of breast cancer biology exacerbated by obesity, including incidence, progression, and therapeutic response. We posit that interception of obesity-driven breast cancer will require interventions that limit protumor signaling from obese adipose tissue and that consider genetic, structural, and social determinants of the obesity–breast cancer link. Finally, we detail the evidence for various dietary interventions to offset obesity effects in clinical and preclinical studies of breast cancer. In light of the strong associations between obesity and breast cancer and the rising rates of obesity in many parts of the world, the development of effective, safe, well-tolerated, and equitable interventions to limit the burden of obesity on breast cancer are urgently needed.
Journal Article
A Low Dose of Dietary Quercetin Fails to Protect against the Development of an Obese Phenotype in Mice
by
Carson, Meredith S.
,
Velázquez, Kandy T.
,
Enos, Reilly T.
in
Adipose tissue
,
Analysis
,
Animals
2016
The purpose of this study was to examine the effect of a 40% high-fat diet (HFD) supplemented with a dietary attainable level of quercetin (0.02%) on body composition, adipose tissue (AT) inflammation, Non-Alcoholic Fatty-Liver Disease (NAFLD), and metabolic outcomes. Diets were administered for 16 weeks to C57BL/6J mice (n = 10/group) beginning at 4 weeks of age. Body composition and fasting blood glucose, insulin, and total cholesterol concentrations were examined intermittently. AT and liver mRNA expression (RT-PCR) of inflammatory mediators (F4/80, CD206 (AT only), CD11c (AT only) TLR-2 (AT only), TLR-4 (AT only), MCP-1, TNF-α, IL-6 (AT only), and IL-10 (AT only)) were measured along with activation of NFκB-p65, and JNK (western blot). Hepatic lipid accumulation, gene expression (RT-PCR) of hepatic metabolic markers (ACAC1, SREBP-1, PPAR-γ), protein content of Endoplasmic Reticulum (ER) Stress markers (BiP, phosphorylated and total EIF2α, phosphorylated and total IRE1α, CHOP), and hepatic oxidative capacity were assessed (western blot). Quercetin administration had no effect at mitigating increases in visceral AT, AT inflammation, hepatic steatosis, ER Stress, decrements in hepatic oxidative capacity, or the development of insulin resistance and hypercholesterolemia. In conclusion, 0.02% quercetin supplementation is not an effective therapy for attenuating HFD-induced obesity development. It is likely that a higher dose of quercetin supplementation is needed to elicit favorable outcomes in obesity.
Journal Article
Development and Characterization of Syngeneic Orthotopic Transplant Models of Obesity-Responsive Triple-Negative Breast Cancer in C57BL/6J Mice
by
Carson, Meredith S.
,
Coleman, Michael F.
,
Albright, Jody
in
Analysis
,
Animal models
,
Antigens
2024
Obesity is an established risk and progression factor for triple-negative breast cancer (TNBC), but preclinical studies to delineate the mechanisms underlying the obesity-TNBC link as well as strategies to break that link are constrained by the lack of tumor models syngeneic to obesity-prone mouse strains. C3(1)/SV40 T-antigen (C3-TAg) transgenic mice on an FVB genetic background develop tumors with molecular and pathologic features that closely resemble human TNBC, but FVB mice are resistant to diet-induced obesity (DIO). Herein, we sought to develop transplantable C3-TAg cell lines syngeneic to C57BL/6 mice, an inbred mouse strain that is sensitive to DIO. We backcrossed FVB-Tg(C3-1-TAg)cJeg/JegJ to C57BL/6 mice for ten generations, and spontaneous tumors from those mice were excised and used to generate four clonal cell lines (B6TAg1.02, B6TAg2.03, B6TAg2.10, and B6TAg2.51). We characterized the growth of the four cell lines in both lean and DIO C57BL/6J female mice and performed transcriptomic profiling. Each cell line was readily tumorigenic and had transcriptional profiles that clustered as claudin-low, yet markedly differed from each other in their rate of tumor progression and transcriptomic signatures for key metabolic, immune, and oncogenic signaling pathways. DIO accelerated tumor growth of orthotopically transplanted B6TAg1.02, B6TAg2.03, and B6TAg2.51 cells. Thus, the B6TAg cell lines described herein offer promising and diverse new models to augment the study of DIO-associated TNBC.
Journal Article
miR155 deficiency aggravates high‐fat diet‐induced adipose tissue fibrosis in male mice
by
Carson, Meredith S.
,
Sougiannis, Alexander T.
,
Bader, Jackie E.
in
Adiponectin - genetics
,
Adiponectin - metabolism
,
Adipose Tissue - metabolism
2017
Noncoding RNAs are emerging as regulators of inflammatory and metabolic processes. There is evidence to suggest that miRNA155 (miR155) may be linked to inflammation and processes associated with adipogenesis. We examined the impact of global miRNA‐155 deletion (miR155−/−) on the development of high‐fat diet (HFD)‐induced obesity. We hypothesized that loss of miR155 would decrease adipose tissue inflammation and improve the metabolic profile following HFD feedings. Beginning at 4–5 weeks of age, male miR155−/− and wild‐type (WT) mice (n = 13–14) on a C57BL/6 background were fed either a HFD or low‐fat diet for 20 weeks. Body weight was monitored throughout the study. Baseline and terminal body composition was assessed by DEXA analysis. Adipose tissue mRNA expression (RT‐qPCR) of macrophage markers (F4/80, CD11c, and CD206) and inflammatory mediators (MCP‐1 and TNF‐α) as well as adiponectin were measured along with activation of NFκB‐p65 and JNK and PPAR‐γ. Adipose tissue fibrosis was assessed by picrosirius red staining and western blot analysis of Collagen I, III, and VI. Glucose metabolism and insulin resistance were assessed by Homeostatic Model Assessment – Insulin Resistance (HOMA‐IR), and a glucose tolerance test. Compared to WT HFD mice, miR155−/− HFD mice displayed similar body weights, yet reduced visceral adipose tissue accumulation. However, miR155−/− HFD displayed exacerbated adipose tissue fibrosis and decreased PPAR‐γ protein content. The loss of miR155 did not affect adipose tissue inflammation or glucose metabolism. In conclusion, miR155 deletion did not attenuate the development of the obese phenotype, but adipose tissue fibrosis was exacerbated, possibly through changes to adipogenic processes. miR155 deletion exacerbates adipose tissue fibrosis, but does not influence metabolic or inflammatory perturbations associated with high‐fat diet‐induced obesity in mice.
Journal Article
Humidity-tolerant rate-dependent capillary viscous adhesion of bee-collected pollen fluids
2019
We report a two-phase adhesive fluid recovered from pollen, which displays remarkable rate tunability and humidity stabilization at microscopic and macroscopic scales. These natural materials provide a previously-unknown model for bioinspired humidity-stable and dynamically-tunable adhesive materials. In particular, two immiscible liquid phases are identified in bioadhesive fluid extracted from dandelion pollen taken from honey bees: a sugary adhesive aqueous phase similar to bee nectar and an oily phase consistent with plant pollenkitt. Here we show that the aqueous phase exhibits a rate-dependent capillary adhesion attributed to hydrodynamic forces above a critical separation rate. However, the performance of this adhesive phase alone is very sensitive to humidity due to water loss or uptake. Interestingly, the oily phase contributes scarcely to the wet adhesion. Rather, it spreads over the aqueous phase and functions as a barrier to water vapor that tempers the effects of humidity changes and stabilizes the capillary adhesion.
When bees carry pollen, it sticks to their legs and it can be carried without being dropped in a range of different humidity conditions. Here the authors find that the adhesive holding the pollen together consists of two phases and the oily phase stabilizes the aqueous phase with respect to humidity changes.
Journal Article
Cloud condensation nuclei activity of six pollenkitts and the influence of their surface activity
by
Lin, Jack J.
,
Nenes, Athanasios
,
Meredith, J. Carson
in
Activation
,
Aerosols
,
Aliphatic compounds
2019
The role of surfactants in governing water interactions of atmospheric aerosols has been a recurring topic in cloud microphysics for more than two decades. Studies of detailed surface thermodynamics are limited by the availability of aerosol samples for experimental analysis and incomplete validation of various proposed Köhler model frameworks for complex mixtures representative of atmospheric aerosol. Pollenkitt is a viscous material that coats grains of pollen and plays important roles in pollen dispersion and plant reproduction. Previous work suggests that it may also be an important contributor to pollen water uptake and cloud condensation nuclei (CCN) activity. The chemical composition of pollenkitt varies between species but has been found to comprise complex organic mixtures including oxygenated, lipid, and aliphatic functionalities. This mix of functionalities suggests that pollenkitt may display aqueous surface activity, which could significantly impact pollen interactions with atmospheric water. Here, we study the surface activity of pollenkitt from six different species and its influence on pollenkitt hygroscopicity. We measure cloud droplet activation and concentration-dependent surface tension of pollenkitt and its mixtures with ammonium sulfate salt. Experiments are compared to predictions from several thermodynamic models, taking aqueous surface tension reduction and surfactant surface partitioning into account in various ways. We find a clear reduction of surface tension by pollenkitt in aqueous solution and evidence for impact of both surface tension and surface partitioning mechanisms on cloud droplet activation potential and hygroscopicity of pollenkitt particles. In addition, we find indications of complex nonideal solution effects in a systematic and consistent dependency of pollenkitt hygroscopicity on particle size. The impact of pollenkitt surface activity on cloud microphysics is different from what is observed in previous work for simple atmospheric surfactants and more resembles recent observations for complex primary and secondary organic aerosol, adding new insight to our understanding of the multifaceted role of surfactants in governing aerosol–water interactions. We illustrate how the explicit characterization of pollenkitt contributions provides the basis for modeling water uptake and cloud formation of pollen and their fragments over a wide range of atmospheric conditions.
Journal Article
Process Intensification in the Pulp and Paper Industry
2023
The pulp and paper industry annually produces over 300 million tons of paper products used across society in print media, packaging, tissue, and hygiene. Transforming wood into useful products involves energy-and resource-intense processing to separate cellulose fibers from wood components, including hemicellulose, lignin, and extractives. Pulp mills, which can operate independently or be integrated with papermaking mills, liberate high-value cellulose fiber from wood through chemical, mechanical, or coupled chemical-mechanical means. Kraft chemical pulping is by far the predominant process used to produce high-strength, purified fiber. This process is based on the digestion of wood using sodium sulfide and sodium hydroxide, which degrade lignin and hemicellulose through alkaline hydrolysis. Challenges of the kraft process that present process intensification (PI) opportunities include its high water and energy intensity, capital expense, and limited yield.
Trade Publication Article
Rheological behavior of highly loaded cellulose nanocrystal/poly(vinyl alcohol) composite suspensions
by
Schueneman, Gregory T.
,
Shofner, Meisha L.
,
Meree, Caitlin E.
in
Alcohol
,
alcohols
,
Bioorganic Chemistry
2016
Recent emphasis on the pilot scale production of cellulosic nanomaterials has increased interest in the effective use of these materials as reinforcements for polymer composites. An important, enabling step to realizing the potential of cellulosic nanomaterials in their applications is the materials processing of CNC/polymer composites through multiple routes, i.e. melt, solution, and aqueous processing methods. Therefore, the objective of this research is to characterize the viscoelastic behavior of aqueous nanocomposite suspensions containing cellulose nanocrystals (CNCs) and a water-soluble polymer, poly(vinyl alcohol) (PVA). Specifically, small amplitude oscillatory shear measurements were performed on neat PVA solutions and CNC-loaded PVA suspensions. The experimental results indicated that the methods used in this study were able to produce high-quality nanocomposite suspensions at high CNC loadings, up to 67 wt% with respect to PVA. Additionally, the structure achieved in the nanocomposite suspensions was understood through component attributes and interactions. At CNC loadings near and less than the percolation threshold, a polymer mediated CNC network was present. At loadings well above the percolation threshold, a CNC network was present, indicated by limited molecular weight dependence of the storage modulus. Overall, these results provide increased fundamental understanding of CNC/PVA suspensions that can be leveraged to develop advanced aqueous processing methods for these materials.
Journal Article
Biomaterials and Regenerative Agriculture: A Methodological Framework to Enable Circular Transitions
by
Stathatou, Patritsia Maria
,
Meredith, J. Carson
,
Garmulewicz, Alysia
in
Agricultural industry
,
Agriculture
,
Biodegradable materials
2023
Biomaterials, used here to signify 100% biobased and biodegradable materials, can offer a promising solution for transitioning away from fossil-based resources, addressing the climate crisis, and combating plastic pollution. To ensure their environmental benefits, biomaterials must derive from regenerative, non-polluting feedstocks that do not compete with food or feed production. From this perspective, agricultural residues and by-products present a favorable feedstock option for biomaterials production. Although this is an improvement over sourcing them from primary crops, the sustainability of underlying agricultural systems must be considered. Furthermore, the nutrient value of biomaterials for specific soil ecosystems is often overlooked despite their compostability. In this research, we investigate the linkages between biomaterials development and regenerative agriculture, a set of farming practices that can effectively sustain the growing human population while enhancing, rather than degrading, ecosystem health. We explore interdependencies between biomaterials’ production and regenerative agriculture for biomass sourcing and nutrient return and suggest a methodological framework to identify mutual benefits. The extent to which regenerative farms can provide biomaterial feedstocks without compromising crop cultivation and ecosystem health is analyzed together with the potential of biomaterials to deliver beneficial nutrients and services to regenerative systems. Applying this framework to the Great Lakes Region, Michigan, USA, an agricultural hub facing environmental degradation and plastic pollution, reveals synergistic linkages that unlock novel circular economy opportunities, including local production of renewable biomaterials for various applications, enhancing food security and bolstering socio-ecological systems.
Journal Article