bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Transplanting an Exercised or Sedentary Microbiota into Gnotobiotic Mice on Global Gene Expression in Gut, Muscle, and Brain Tissue
Authors: Mailing Lucy J. , Allen Jacob M. , Wang Selena S. , Kashyap Purna , White Bryan A. , Woods Jeffrey A. 
Published: June 2021

IntroductionThe gut microbiota is intricately connected with host health and is known to influence gene expression across multiple organ systems. Both animal and human longitudinal studies have demonstrated that exercise has independent effects on the composition and functionality of the gut microbiota. Previous studies performed by our group have also shown that transplant of an “exercised” microbiota into germ‐free mice confers enhanced protection against colitis compared to transplant of a “sedentary” microbiota. In this study, we assessed how an “exercised” microbiota transplant impacts global gene expression in gut, brain, and muscle tissue compared to a “sedentary” microbiota transplant.MethodsDonor mice received access to a running wheel (n=10) or remained without access (n=9) for six weeks prior to euthanasia. Donor cecal contents were pooled by activity group and transplanted into two separate groups of recipient germ‐free mice (n=16 for each group). After five weeks of gut microbial colonization, recipient mice were sacrificed, and tissues were collected. Total RNA was isolated from the distal colon, soleus muscle, and hippocampus. Four representative mice were chosen from each group for whole transcriptome analysis (RNAseq) of these tissues.Anticipated ResultsWe hypothesize that mice that received an “exercised” microbiome will have different global gene expression profiles than those that received a “sedentary” microbiome. We predict that genes related to immune function, cellular metabolism, and gut barrier function may be particularly affected by transplant of the “exercised” microbiome.Support or Funding InformationThis work supported by a grant from the Mayo Clinic‐University of Illinois Alliance for Technology‐based Healthcare.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Shocking! The Effect of TSST‐1 in Toxic Shock Syndrome
Authors: Arnholt Mark , Munzenmaier Diane H , Anderson Evelyn , Benson Cassidy , Brown Julia , Colwell Margaret , Colwell Theodore , Flanagan Michael , Hautala Lauren , Hennes Delaney , Hoffmann Gabriel , Kennedy Cara , Lisowski Leah , Stoeckmann Tate , Witt Emma , Zuern Rachel 
Published: June 2021

Almost 20% of children who die of Sudden Infant Death Syndrome have a protein called Toxic Shock Syndrome Toxin‐1 (TSST‐1), produced by Staphylococcus aureus. This protein is also responsible for toxic shock and food poisoning. S. aureus produces this superantigen TSST‐1 to divert the immune system and multiply rapidly inside the body. TSST‐1 contains 194 amino acids and three domains. Identical domains A, B, and C consist of a larger alpha‐helix, residues 152‐168, along with two beta‐sheets, and three shorter alpha helices. The long alpha helix defines the protein as a superantigen. Antigen‐presenting cells, such as macrophages, contain Major Histocompatibility Complex class II. These domains are bound to T‐cell receptor beta sheets by TSST‐1, bypassing the normal interface, and activating up to 24% more than the average immune response. Despite TSST‐1 having no disulfide bridges, therefore lack of thermal denaturation resistance, TSST‐1 thrives in the human body due to an immune system distraction. TSST‐1 can move through mucous membranes, allowing S. aureus to disrupt the immune response without being inside the body. In the wild form of TSST‐1, His‐135 located adjacent to the long alpha‐helix is mutated to Alanine, creating mutant TSST‐1, making the superantigen inactive for reasons unknown. The HUHS SMART Team (Students Modeling A Research Topic) Team has designed a model of the wild form of TSST‐1 with 3D printing technology to investigate structure_function relationships. By studying how TSST‐1 interacts with the immune system, advances can be made to control the spread of these pyrogenic toxin superantigens.Support or Funding InformationThe MSOE Center for BioMolecular Modeling would like to acknowledge and thank the National Institutes of Health Clinical and Translational Science Award (NIH_CTSA UL1RR031973) and the Milwaukee School of Engineering for their support in funding the 2018_2019 SMART Team program.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Murine Mouse Models of Metastatic Colorectal Cancer in Lungs: Foci Counts in Three Dimensions
Authors: Monteith Corey , Jackson Hunter , Mechanic Jordan , Vemuri Venkata , Daniel Cody , Parker Kristy , Martinez Morgan , Scott Katherine , Farahani Navid , England Steve 
Published: June 2021

In standard histological slide preparations, only a few representative samples are taken, which introduces sampling bias and necessarily eschews information about the full tissue sample. However, it is possible to obtain a full 3D data set of an entire tissue sample using the Knife Edge Scanning Microscope (KESM), an automated simultaneous sectioning and imaging microscope. In this study, we performed manual counts of metastases of colorectal cancer in mouse model lungs stained with India ink and hematoxylin and eosin, which were then sectioned and imaged in their entirety. We were able to get more accurate count of tumor foci than the current standard of surface nodule count can allow; multiple tumor foci were buried hundreds of microns deep into the parenchyma and hence not grossly visible from the surface. Volumetric analysis of whole samples also revealed unusual tumor morphology and permitted the visualization of unique architectural features where multiple tumor foci had grown together. Following the manual count of tumor foci, we developed a semi‐automated algorithm that could increase the efficiency of screening for foci, and create the opportunity for digital 3D reconstruction and morphology interrogation. Without access to a full dataset of the lungs, it is impossible to determine true foci number or morphology.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Bile Acid Excess Impairs Thermogenic Function in Brown Adipose Tissue
Authors: Zhou Weinan , VanDuyne Philip , Riessen Ryan , Akinrotimi Oludemilade , D'Souza Shawn , Anakk Sayeepriyadarshini 
Published: June 2021

Obesity is a major epidemic and is associated with metabolic dysfunction leading to excess accumulation of fat. Bile acids (BAs) are body's natural detergents that facilitate fat digestion. Additionally, BAs act as signaling molecules regulating metabolism and can protect against obesity. Despite, several studies have demonstrated that elevated BAs promote energy expenditure, it remains unknown if BAs are present in brown adipose tissue (BAT) and can they directly affect BAT function. Here, we show that BAs, BA transporters and de novo synthetic enzymes are detected in BAT. Notably, the global farnesoid X receptor; small heterodimer partner double knockout (DKO) mice, a model for BA overload, exhibit higher BAs levels in BAT than the control mice. DKO mice exhibit lower body temperature, decreased mitochondrial DNA content, and altered activities of oxidative phosphorylation enzyme complexes. Consistent with this phenotype, we find that excess BAs impair BAT mitochondrial function and can cause thermogenic dysfunction. Importantly, when low physiological BA levels are used to treat brown adipocytes, we do not find mitochondrial defects. However, upon treatment with pathological BA concentrations, differentiated primary brown adipocytes in vitro show reduced mitochondrial membrane potential and concomitant reduction in thermogenic gene expression profile. We have shown that DKO mice are resistant to fat accumulation both on normal chow and when challenged with a high‐fat diet. This protection is significantly lost when the mice are housed at thermoneutral conditions indicating that by having leaky mitochondria and poor thermoregulation, DKO mice are protected against accumulating fat. Overall, we show for the first time the presence of BA metabolic machinery in the BAT and identify that elevated levels of BAs can cause thermogenic dysfunctions. Weinan Zhou and Philip VanDuyne contributed equally to this work.Support or Funding InformationStartup funds from the University of Illinois at Urbana‐Champaign, and R01 DK113080 from NIDDK.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Analysis of an Omega 6:3 Balanced Diet Impact on Hibernation Behavior and Cortisol of Captive Arctic Ground Squirrels
Authors: Mikes Monica L , Rice Sarah A , Bibus Doug , Drew Kelly L 
Published: June 2021

Arctic Ground Squirrels (AGS) are widely studied in laboratories for their capability to sustain low metabolic rates and temperatures without enduring debilitating bodily harm. A specific range of omega 6 polyunsaturated fatty acids (PUFAs) has been shown to improve captive hibernation by increasing torpor bout length and depth of hibernation across multiple species (Geiser 1993, Frank 2008). To our knowledge, only three studies have investigated the impact of omega 3 fatty acids on hibernation behavior with varying results (Giroud 2018, Frank 2004 and Hill and Florant 2000). Our prior findings show wild AGS plasma have a balanced omega 6 to 3 fatty acid profile (1.3:1), but no one, to our knowledge, has tested the impact of this specific PUFA ratio on captive AGS. We hypothesize that substituting a high omega 6:3 (8:1) diet for a balanced diet (1.3:1) would increase the length of torpor bouts, entrance timing into hibernation and decrease cortisol.Wild juvenile AGS (12 f, 12 m) were evenly distributed to two groups: a balanced omega 6:3 ratio diet (1.3:1) and a control diet of Mazuri rodent chow with an omega 6:3 ratio of (8:1). Animals were fed 47g daily of their diets until first torpor bout and food was withdrawn. Animals were instrumented with abdominal temperature I‐buttons in early August. White adipose tissue (WAT) and plasma were sampled longitudinally at fall (early August at the time of surgery) and winter (mid‐December at time of euthanasia). Animals were euthanized in three stages of the torpor bout cycle: early torpor, late torpor, and full arousal.WAT was analyzed a modified lipid dense tissue protocol using solid phase extraction. Cortisol was measured using RIA. Early August levels of cortisol were 1.4× higher in the animals supplemented with the balanced omega 6:3 diet (p<0.0001). Preliminary temperature data indicates that the balanced diet and control diet AGS do not significantly differ in the number of hibernation days, entrance timing into hibernation or torpor bout length. Additionally, preliminary data indicates a significant increase in body weight of females on a balanced omega 6:3 diet during fall (p<0.013) and winter (p<0.049).Preliminary data indicates the balanced diet does not negatively impact hibernation behavior. The unexpected increase in cortisol in the balanced omega 6:3 ratio fed diet may reflect normal physiological levels rather than stress. Cortisol functions as a stress indicator, but also enhances fat deposition, which is an essential task prior to hibernation.Support or Funding InformationThis work was supported by NIH 20GM103395, UL1GM118991, TL4GM118992, or RL5GM118990. This work was performed in conformance with the FASEB Statement of Principles for animals used in research.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
LPS‐induced mTORC1 Signaling Activates Lipid Raft‐Actin Cytoskeletal Interactions for Phagocytosis through SREBP‐1a
Authors: Lee Jae‐Ho , Kim Do Young , Lee Sun Hee , Song Dae‐Kyu , Bae Jae‐Hoon , Im Seung‐Soon 
Published: June 2021

There is a growing appreciation for a fundamental connection between lipid metabolism and the immune response. Macrophage phagocytosis is a signature innate immune response to pathogen exposure and cytoplasmic membrane expansion is required to engulf the phagocytic target. The sterol regulatory element binding proteins (SREBPs) are key transcriptional regulatory proteins that sense the intracellular lipid environment and modulate expression of key genes of fatty acid and cholesterol metabolism to maintain lipid homeostasis. In this study, we show that TLR4 dependent stimulation of macrophage phagocytosis requires mTORC1‐directed SREBP‐1a dependent lipid synthesis. We also show that the phagocytic defect in macrophages from SREBP‐1a deficient mice results from decreased interaction between membrane lipid rafts and the actin cytoskeleton presumably due to reduced accumulation of newly synthesized fatty acyl chains within major membrane phospholipids. We show that mTORC1 deficient macrophages also have a phagocytosis block downstream from TLR4 signaling, and interestingly, the phagocytosis deficiency in both SREBP‐1a and mTORC1 mutant macrophages can be restored by ectopic SREBP‐1a expression. Taken together, these observations indicate SREBP‐1a is a major downstream effector of TLR4‐mTORC1 directed interactions between membrane lipid rafts and the actin cytoskeleton that are required for pathogen‐stimulated phagocytosis in macrophages.Support or Funding InformationThe National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP)(2016R1A2B4008516). The National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (2014R1A5A2010008).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Activation of Histone Deacetylase 6 (HDAC6) in the diabetic retina and in retinal endothelial cells exposed to glucidic stress, promotes oxidative stress through suppression of the thioredoxin system
Authors: Abouhish Hossameldin Abdelmonem , Thounaojam Menaka C , Jadeja Ravirajsinh N , Martin Pamela M , Khriza Mohamed Mhmoud , Bartoli Manuela 
Published: June 2021

Retinal microvascular dysfunction characterizes the pathophysiology of diabetic retinopathy (DR), a common complication of diabetes and a leading cause of blindness in the World. Oxidative stress and inflammation have been implicated as major pathogenic hubs for the induction and progression of DR. Reduced endogenous antioxidant activities within the retinal microvasculature can significantly contribute to oxidative stress in the diabetic retina. We have previously shown that diabetes inhibits the thioredoxin system (TrxS) and others have shown that the cytosolic histone deacetylase 6 (HDAC6) can promote oxidative stress in a not yet understood mechanism. Here we have investigated the role of HDAC6 in regulating the TrxS in the diabetic retinal microvasculature. HDAC6 expression and activity were assessed by immunoblotting and fluorimetric assay (respectively) in retinas of streptozotocin‐induced diabetic rats (STZ‐rats, 8 weeks of diabetes) and in primary culture of human retinal endothelial cells (HuREC) exposed to disease‐relevant glucose levels (HG=25mM D‐glucose) for 48 hours. Changes in TrxS were monitored by assessing the expression and activity of its functional unit, thioredoxin‐1 (Trx‐1), by immunoblotting and a commercially available fluorimetric assay, in STZ‐rats retinas and in HuREC exposed to HG. Some experiments in HuREC were conducted also in presence of 5μM of the specific HDAC6 inhibitor tubastatin A. CellROX assay and dot‐blot assessing 5‐nitrotyrosine (5‐NT) and 4 hydroxynonenal (4‐HNE) were used to measure oxidative stress in our experimental groups. HDAC6 expression and activity were found significantly elevated in retinas of STZ‐rats compared to normal age‐matched controls and in HuREC exposed to HG, but not to normal glucose (5mM D‐glucose) or the osmotic control L‐glucose (25mM). At the same time Trx‐1 expression was increased in diabetic retinas and in HuREC exposed to HG, whereas its activity was significantly decreased. Parallel to loss of Trx‐1 activity and increased HDAC6 expression and activity, we also found that oxidative stress parameters were also elevated. In HuREC, tubastatin A was able to block HG‐induced up‐regulation of oxidative stress parameters while up‐regulating Trx‐1 activity and normalizing its expression. In summary, our data confirm previous observations on the role of HDAC6 in promoting oxidative stress and disclose HDAC6 role in suppressing Trx‐1 activity. Therefore, our results, support HDAC6 pathogenic role in promoting oxidative stress in the diabetic retinal microvasculature and its implication in the pathogenesis of diabetic retinopathy.Support or Funding InformationEY022416This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Avoiding a Swelled Head: Aquaporin‐4 and Brain Edema
Authors: Shelton Katelyn , Gross Gabriela , Baca Mackenzie , Kaka Nornubari 
Published: June 2021

Aquaporins are integral membrane proteins that serve as water channels. Aquaporin 4 (AQP4) is an aquaporin specific to the brain. Besides working as the “plumbing system” to allow water to diffuse across the membrane, it also prevents the passage of ions and other solutes. Aquaporin‐4 works in a bundle of four aquaporin monomers to form a tetramer and is highly expressed within astrocytes (cells in the CNS that help maintain homeostasis) and within the blood‐brain barrier. The blood‐brain barrier is a lipophilic membrane which permits lipid penetration freely while preventing water diffusion. Aquaporin‐4 regulates water circulation of the brain and does not require any energy to function, allowing for the simple diffusion of water. AQP4 has been shown to facilitate astrocytic edema and is responsible for the reabsorption of extracellular edema fluid. Symptoms of cerebral edema include nausea, vomiting, Aquaporin‐4 is supposed to maintain the fluid levels through the spinal cord but the real question is how does it do that in the structure it appears to be. Instead of explaining the function of the Aquaporin‐4, we are going to show it through a model we have created. Cerebral edema can occur when a clot is preventing blood access to the brain; the immune system begins to attack and exert fluids via AQP4, resulting in excess fluid. That edema therefore increases pressure within the skull preventing blood from flowing to the brain and occasionally leads to a stroke. If AQP4 can be targeted, then edema can significantly be reduced and become less of a risk to injured brain tissue.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The Snow Flea Antifreeze Protein and Cryopreservation
Authors: MacGillivray Brendan , Greig James , Cobo Nicolás Alonso , Chow Alyssa , Han Brian , He Lucy , Mark‐George Matthias , Niu Zimu , Wai Ewan , Wang Yier , Xiao Mason 
Published: June 2021

Hypogastrura harveyi (snow fleas) produce a glycine‐rich antifreeze protein which enables it to survive in environments that would otherwise freeze its body fluid. Snow flea antifreeze protein (sfAFP) is a 6.5 kDa monomeric protein made of six alpha helices linked by hydrogen bonds and disulfide bridges. The protein's amino acid sequence has a frequent glycine‐x‐y amino acid pattern, where the x amino acid is also glycine 50% of the time and the y amino acid is either hydrophobic or hydrophilic. The hydrophobic side of sfAFP binds to the surface of seed ice crystals, breaking up the ice surface into smaller areas and preventing the further binding of water molecules due to the Kelvin effect. Other AFP's have been shown to be efficacious in improving the preservation of rat hearts, leading to the yet‐untested hypothesis that sfAFP's are also able to prolong the cryopreservation of organs. The Ashbury MSOE Center for BioMolecular Modeling SMART Team used 3‐D modeling and printing technology to examine structure‐function relationships of sfAFP when bonding to an ice lattice.Support or Funding InformationMSOE ‐ Center for Biomolecular Modelling ‐ co‐sponsor Diane MunzenmaierThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Qualitative and Comparative Analysis of Antemortem vs. Postmortem Root Hair Banding Use in Forensic Science
Authors: Wiggins Abigail Grace 
Published: June 2021

Hair is one of the most important types of evidence in Forensic Science. Hair can be used to place a victim, and an assailant, in the same location. One method utilizes root banding of a hair sample, recovered from a victim or crime scene, that are analyzed using microscopy. Postmortem root banding is observed in samples collected from deceased humans. This methodology is used to determine if the evidence came from a living, or deceased victim. However, postmortem root banding patterns have recently been observed in antemortem anagen hair samples, now referred to as antemortem root banding. Further characterization and comparison between the two types of root banding is needed to assist in determining the type of investigation required in forensic cases; missing persons or body recovery missions. The objective of this research is to better differentiate postmortem and antemortem root banding. Laboratory created antemortem root banding data will be characterized by the banding location on the hair follicle, coloration by stage, and width compared to corresponding postmortem root banding. This work is expected to contribute to advancements in the field of Forensic Science and strengthen the ability to differentiate postmortem and antemortem root banding. The legal argument of antemortem root banding, and postmortem root banding evidence is easily dismissible in a court of law. The ability to differentiate between the two types of root banding patterns will afford more reliable evidence in the judicial system.Support or Funding InformationDepartment of Mathematics and Science, Saint Leo University, Saint Leo, FL 33574This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.