bluuebunny/crossref_metadata_2025_split huggingface dataset:
Collecting duct NOS1 activation is necessary for increased GFR in response to high salt diet
Authors: Allan John Miller , Pollock David M. , Hydnman Kelly A. , Pollock Jennifer S. 
Published: June 2021

We previously reported that nitric oxide synthase‐1 (NOS1) in the collecting duct (CD) is critical for maintaining fluid‐electrolyte balance during high salt diet. Lack of NOS1 in the CD (CDNOS1KO) results in reduced sodium excretion, urine output, and urinary nitrite/nitrate excretion compared to control mice after 1 day of a high salt diet. By day 7 of a high salt diet, CDNOS1KO mice display significantly increased systolic blood pressure with normalized sodium excretion. We also previously reported that after 7 days of high salt diet there is inappropriate suppression of plasma and urinary aldosterone excretion, renal angiotensin II levels, and CD ENaC activity. This inability to appropriately suppress renal angiotensin II and systemic aldosterone with high salt diet in CDNOS1KO mice lead us to hypothesize that the loss of activation of CD NOS1 during high salt diet challenges blunts the physiological renal hemodynamic response to high salt diet. The purpose of the current study was to determine if CDNOS1KO mice on high salt diets have attenuated glomerular filtration rate (GFR) response. To test this, GFR was measured by transdermal FITC‐sinistrin clearance in conscious male control and CDNOS1KO mice on sodium deficient (LS, n=4), normal salt (NS, n=11) or after 1 day and 7 days of high salt (HS1, n=4 and HS7, n=10) diets. On LS and NS, GFR was similar between control (LS: 263 ± 14 ml/min, NS: 224 ± 6 ml/min) and CDNOS1KO mice (LS: 237.2 ± 10 ml/min, NS: 218 ± 10 ml/min) (Pgenotype = 0.4, Pdiet = 0.7, Pgenotypexdiet = 0.3). HS1 control mice had a significant increase in GFR (333 ± 10 ml/min, P=0.008), while GFR remained unchanged in CDNOS1KO mice (255 ± 23 ml/min, P=0.2) compared with LS. HS7 control and CDNOS1KO mice had similar levels of GFR (251 ± 16 and 291 ± 27 ml/min, respectively). Taken together these data indicate, that CD NOS1 is critical for the adaptation to a high salt diet, such that CDNOS1KO mice are volume expanded, have inappropriately high RAAS activation, and fail to increase GFR. After a few days of high salt diet, blood pressure is increased resulting in a rightward shift in the pressure natriuresis curve, with GFR and sodium excretion normalized to control levels. In conclusion, CD NOS1 activation is critical for regulation of tubular and hemodynamic pathways during consumption of HS diets.Support or Funding InformationK01‐DK‐105038 KAH, HL136936 JSP and DMP.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Alterations in the intestinal microbiota contribute to the gastrointestinal toxicity of the anti‐rejection drug mycophenolate mofetil
Authors: Flannigan Kyle L. , Pereira Sheldon K. , Taylor Michael R. , Alston Laurie , Wang Xuemei , Rioux Kevin P. , Galipeau Heather J. , Workentine Matthew L. , Greenway Steven C. , Hirota Simon A. 
Published: June 2021

Transplantation is curative for end‐stage organ failure but requires potent immunosuppressive medications to prevent rejection including the immunosuppressant mycophenolate mofetil (MMF). While MMF is effective as maintenance therapy, it is commonly associated with gastrointestinal (GI) side effects (e.g. diarrhea, rapid weight loss, colitis) which can necessitate its discontinuation, increasing the chances of graft failure and rejection. While the mechanism(s) contributing to MMF‐related GI toxicity are not understood, we recently reported a clinical case where MMF complications were associated with shifts in the composition of the intestinal microbiota. Thus, in the current study, we hypothesized that the GI toxicity associated with MMF was dependent on the intestinal microbiota. To test this, we fed C57BL/6 mice chow containing MMF and assessed a variety of outcomes. Mice consuming MMF exhibited significant weight loss (>20% after 9 days), which reflected a loss of body fat and lean muscle mass. This was accompanied by marked inflammation of the colon. MMF treatment also promoted changes in gut microbial composition, demonstrated by a loss of overall diversity, expansion of Proteobacteria and loss of beneficial bacterial genera. PICRUSt predicted gene counts identified several components of LPS biosynthesis that were significantly upregulated following MMF treatment. This was associated with an increase in fecal and serum levels of LPS in MMF‐treated mice. Treatment with broad‐spectrum antibiotics prevented and reversed MMFinduced weight loss and colonic inflammation. Importantly, MMF did not induce intestinal toxicity in germ free mice. Our results reveal that MMF triggers GI toxicity by altering the intestinal microbiota and highlights the microbiota as an important driver of the side‐effects associated with immunosuppressive anti‐rejection therapies.Support or Funding InformationAlberta Innovates, Canadian Institutes of Health Research, Canadian Foundation for Innovation, Dr. Lloyd Sutherland Fund in IBD/GI Research, Cumming School of MedicineThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Using a Zebrafish Model to Study the Gut Microbiota's Effect on the Brain's Neurochemistry and Behavior.
Authors: Ball Alexander G. , Bell Emily A. , Sienerth Karl , Uno Jennifer K. 
Published: June 2021

Despite the vast amount of Autism Spectrum Condition (ASC) research, the cause of ASC remains unknown. Recently, several studies indicate a link between ASD and the gut microbiota, a complex bacterial ecosystem present in the digestive tract of animals. The gut microbiome is an important component of the gut‐brain axis, a bi‐directional communication pathway between the gastrointestinal tract and the brain. Additionally, the gut microbiome is a key regulator of the serotonin, which has been found in higher concentrations in the autistic individual's blood serum. Serotonin is involved in neuron growth and may be responsible for the alterations in brain structure seen in autistic individuals. This study employs a zebrafish model to examine how dysregulation of the gut microbiome influences serotonin levels in the brain and how that potentially impacts social interaction. We hypothesize that alterations in the gut microbiota will produce higher levels of serotonin in the brain and therefore cause alterations in behavioral interactions. Adult zebrafish were administered amoxicillin, or an ampicillin/clindamycin combination and the shoal area was measured to examine the zebrafish's social behavior. Intestinal bacterial‐DNA was extracted, and bacterial phyla were examined and quantified by qPCR. Serotonin levels in a zebrafish brain were measured directly though fluorescence spectroscopy and indirectly, through serotonin receptor expression. Results confirmed amoxicillin significantly decreased the quantity and diversity of the intestinal bacterial communities by 60% (p value < 0.05). Antibiotic treatment also correlated to behavioral changes in the fish, illustrated by the 50% larger shoal areas (p value <0.05). The results from this study will help shed light on a complex neurodevelopmental condition.Support or Funding InformationThis work was funded by Elon University.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Four Weeks of Intermittent Fasting Improves Sleep Quality, Decreases Stress Levels, Improves Quality of Life, and Enhances Body Composition in a Middle Aged Male: A Case Study
Authors: Bains Gurinder , Silver Sasha , Wilson Christine , Garcia Henry , Lohman Everett , Berk Lee 
Published: June 2021

IntroductionThe obesity epidemic, affecting nearly 78 million adults and 13 million children in the United States, is linked to increased propensity for metabolic syndrome, Type 2 diabetes, heart disease, and stroke. Weight loss and improvement of body composition through physical activity and dietary modifications can help decrease the risk for these obesity‐related diseases. One alternative method of caloric restriction is Intermittent Fasting.PurposeDetermine the effect of 4 weeks of Intermittent Fasting on sleep quality, stress, quality of life, and body composition.MethodsA forty‐seven year old male completed a four‐week session of Intermittent Fasting. The subject is a non‐smoker, does not drink alcohol, completed higher education, works in a University setting, and is considered otherwise healthy. The subject was required to perform physical activity for a minimum of three times per week for 30 minutes per session. The subject fasted 16 hours from the time of his last meal of the evening to the start of his first meal the following day. Once the fast was broken, the subject was required to consume his daily caloric intake within an 8‐hour period, with no requirements on number of meals. Basal Metabolic Rate and Total Daily Energy Expenditure was utilized to calculate daily caloric amounts and macro nutrient goals. The Pittsburgh Sleep Quality Index and the Cohen Perceived Stress Scale were administered to determine sleep quality and self‐awareness on stress levels. Quality of Life was assessed through the 36‐Item Short Form Survey Instrument (SF‐36). Body composition was determined using the InBody 270 analyzer.ResultsAt the conclusion of the 4 week intervention, there was an improvement in sleep quality (46.9%), reduction in stress (22.6%), and overall improvement in quality of life. In addition, there was a decrease in weight (4.9 kg), BMI (2.4 kg/m2), body fat (3.1 %), and waist circumference (5.1 cm), respectively.ConclusionWe suggest the health benefits of Intermittent Fasting is a viable option to help decrease the risks of obesity related disease, decrease weight, and lower body fat. Results indicate that four weeks of Intermittent Fasting should be considered to improve sleep quality, decrease stress, improve quality of life, and enhance body composition. Our case study shows potential health related benefits from Intermittent Fasting that can be integrated into whole person wellness programs. Further research is needed to expand these positive findings.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Attenuation of High Glucose/High Insulin‐Induced Muscle Insulin Resistance by Rosemary Extract
Authors: Shamshoum Hesham , Tsiani Evangelia 
Published: June 2021

Insulin is a key hormone affecting metabolism and plays a major role in the regulation of glucose homeostasis. Skeletal muscle accounts for ~80% of postprandial glucose disposal and is thus the major organ of glucose uptake. Insulin increases muscle glucose uptake by increasing the translocation of intracellularly stored GLUT4 glucose transporters to the plasma membrane through the phosphatidylinositol‐3 kinase (PI3K)/Akt signaling pathway. Impaired PI3K/Akt signaling is associated with insulin resistance (IR) in skeletal muscle, leading to chronically elevated blood glucose levels and followed by a compensatory rise in insulin levels. The elevated glucose and insulin levels, in turn, exacerbate IR. Polyphenols are phytochemicals derived from natural plant sources that were found to have antioxidant, anti‐inflammatory, anti‐cancer and anti‐diabetic effects.Rosemary extract (RE), rich in polyphenols, contains carnosic acid (CA), carnosol (COH) and rosmarinic acid (RA), which have been shown to counteract insulin resistance in both in vitro and in vivo animal models. However, the mechanisms involved are not known. Therefore, the aim of this study is to investigate the effects of RE on high glucose (HG)/high insulin (HI)‐induced skeletal muscle insulin resistance and the molecular mechanisms involved. Glucose uptake was assessed using [3 H]‐2‐deoxy‐d‐glucose. Total and phosphorylated levels of Akt and IRS‐1 were measured by immunoblotting. Exposure of L6 myotubes to 25mM glucose/100nM insulin for 24 h, to mimic hyperglycemia/hyperinsulinemia, abolished the acute insulin‐stimulated glucose uptake (I: 180±10.43, HG/HI + I: 108 % of basal). In addition, HG/HI attenuated the insulin‐stimulated Akt phosphorylation, while increased IRS‐1 Ser 636/639 phosphorylation indicating insulin resistance. Importantly, treatment with RE (5 μg/ml, 24 h) significantly restored the insulin‐stimulated glucose uptake (HG/HI + RE + I: 184%). Our data indicate a potential of RE to counteract muscle insulin resistance. The focus of our research is to investigate the mechanism involved in mediating this effect of RE.Support or Funding InformationSupported by a Natural Sciences and Engineering Research Council of Canada (NSERC) grant to ETThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Histological Study of Bovine Hoof Development
Authors: Hung Jun , Grossman Ari , Rodriquez‐Sosa Jose R. , Ruiz Saul , Hall Margaret I. , Plochocki Jeffrey H. 
Published: June 2021

The ungulate hoof is a complex integumentary organ formed by epidermal and dermal layers that primarily serve to protect the enclosed digits. Each layer serves specific functions and their histological structure may vary throughout prenatal and postnatal development. Importantly, epidermal regions of the hoof interface with the underlying connective tissue layers of the dermis. This tissue interaction includes a system of dermal laminae that interdigitate with the epidermally‐derived horn to increase contact area between the tissues, thereby anchoring the outer hoof to the distal phalanx. Functionality of this system is necessary at birth to reduce risk of lameness, which is associated with bovine mortality. However, the development of this tissue interaction has not been thoroughly investigated in the cow. Here, we study hoof development in bovine fetuses (n=21) aged 60, 80, 110, and 165 days of gestation, which lasts approximately 283 days. Hindlimb hooves were dissected, sectioned at 5 microns, and stained with H&E. Micrographs of the sections show the major layers are present by day 60 of development. Distances between laminae vary slightly with age, but the morphological complexity of the laminar system is similar among the age groups, suggesting growth and maturation of these structures occurs earlier in development, closer to the time of organogenesis. Thus, the tissue morphology necessary to provide mechanical stability to the bovine hoof are present early in prenatal development.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Links between Anatomy, Systems biology, Epigenetics, etho‐eco‐morphological mismatches, evolutionary trends, and organism behavior: a unifying view of anatomical evolution
Authors: Diogo Rui 
Published: June 2021

It is a puzzling paradox that eco‐morphological mismatches occur so frequently in an evolutionary process that often leads to macroevolutionary trends and in which organisms are said to be ‘designed’ for the habitats they inhabit. Here I present a new framework ‐ Organic Nonoptimal Constrained Evolution (ONCE) ‐ to address this paradox, and to explain why organisms look as they look: organisms themselves, and in particular their behavior, are the major active players of evolution. That is, within this framework, internal factors can both decrease and increase plasticity/hidden variation and therefore, together with epigenetic factors influenced by the external environment, can allows organisms to shift their behavior, for instance as a response to environmental changes. Importantly, due to behavioral persistence related to behavioral/ecological inheritance, organisms as diverse as bacteria, plants and animals help to construct their own niches, thus being crucial to direct evolution. Darwinian natural (external) selection then comes into play as a secondary ‐ but still crucial ‐ player. That is, due to organismal behavioral persistence, the random mutations/epigenetic factors that happen to be advantageous within the niches constructed by the organisms will be selected, further directing evolution and increasing the match between behavior, phenotype, and environment. This process can extend for long periods of time, leading to macroevolutionary morphological trends and further increasing this match, potentially resulting in successful phenotypic overspecialization. However, behavioral persistence, loss of plasticity due to natural selection, genetic drift, overspecialization, and internal constraints can often make it difficult for the organisms to respond behaviorally and/or anatomically to new environmental changes, resulting in potential mismatches between behavior, ecology and form, and eventually in extinction. This new framework about anatomical evolution therefore bridges the gap between ideas that have been long considered to be opposing views of biology since Aristotle, including internalism and externalism, Cuvier's vs. Geoffroy's take on form and function, Darwinism and Lamarkism, the ideas of Baldwin, Waddington and Goldschmidt, and current Evo‐Devo ideas such as a physicalist framework, niche construction and epigenetic plasticity. This talk therefore covers ‐ and aims to link ‐ areas as diverse as evolutionary developmental biology, paleontology, evolutionary biology, comparative anatomy, ecomorphology, functional anatomy, ecology, ethology, biological anthropology, evolutionary medicine and history and philosophy of biology.Support or Funding InformationNAThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Smell Loss (Hyposmia) is a Lifelong, Chronic Sensory Disease
Authors: Henkin Robert 
Published: June 2021

Smell loss (hyposmia) occurs in about 7% of the U.S. population. It is comprised of a heterogeneous group of diseases with three major groupings: direct (brain or nerve injury), congenital (genetic factors) or acquired (biochemical causes). Smell loss most commonly occurs with acquired factors with specific biochemical pathology initiating the disorder associated with a variety of clinical conditions, e.g., post‐viral infection, chronic allergic rhinitis, head injury, inhalational anesthesia and other conditions. The biochemical mechanisms underlying both acquired and congenital hyposmia relate to inhibition of olfactory epithelial receptor cell function due to altered secretion of specific growth or transcription factors in nasal mucus which are required to initiate olfactory receptor stem cell generation and perpetuation. Some growth/transcription factor secretions are decreased to cause these dysfunctions. They include hormones, vitamins, trace metals and a group of biochemical growth/transcription factors – cAMP, cGMP and sonic hedgehog. Some growth/transcription factor secretions are increased to cause these dysfunctions ‐ these are “death factors” which act to inhibit olfactory receptor function. These include cytokines such as TNFalpha. Treatment with oral or intranasal phosphodiesterase (PDE) inhibitors increase secretion of decreased growth/transcription factors and decrease secretion of “death factors” such that stem cells in the olfactory epithelium are stimulated to initiate receptor growth and development. Treatment with PDE inhibitors are required to provide continual stimulation of these stem cells since they initiate the cellular activity by which these receptors (which do not contain blood vessels, lymphatics or exhibit mitosis but turn over rapidly, commonly on a daily basis) are stimulated. In this sense, hyposmia is a chronic disease process similar to diabetes or arthritis. While the disease can be treated it is a lifelong, chronic disorder.Support or Funding InformationNAThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The effect of cocaine cue re‐exposure after prolonged cocaine self‐administration and forced abstinence on DNA methylation and mRNA expression in the rat dmPFC
Authors: Ploense Kyle L. , Vieira Philip , Carr Amanda , Purpura Mari , Kippin Tod 
Published: June 2021

Cocaine addiction is a chronic relapsing disorder whereby cocaine craving in response to drug related cues persists, and even intensifies through protracted drug‐free abstinence periods. Studies employing animal models observe cocaine‐seeking patterns that are similar to human addicts. Additionally, there are long term changes in neuron structure, receptor function, and neurotransmission associated with abstinence from cocaine in humans and animals. DNA methylation is an epigenetic modification to the DNA structure that mediates mRNA expression to confer different cell types, but has recently been implicated in learning and memory mechanisms. The long‐term control that DNA methylation has over gene expression in animals makes it a prime candidate for controlling gene expression over the course of abstinence in animals with previous drug experience. To test this, I trained rats to self‐administer either saline (1 h per day) or cocaine (6 h per day) for 15 days, then exposed them to 60 days of forced abstinence. After abstinence half of the rats were put back in self‐administration chambers and re‐exposed to cues for 2 h, while the other half were left in their home cages. After the cue manipulation, all rats were sacrificed, the dmPFC was dissected out, and DNA and mRNA were extracted. Methylated DNA was purified using methylated DNA immuno‐precipitation, and mRNA was reverse‐transcribed into cDNA; levels of each were then quantified via digital PCR procedures. Interestingly, I observed cue‐induced changes in DNA methylation within Homer2, Dlg4, Npas4, and Grin1 promoter regions. These context‐specific changes indicate that DNA methylation is much more dynamic than previously shown. Additionally, I saw changes in mRNA expression for Homer2, Dlg4, and Npas4 that appear to be highly reflective of the changes in DNA methylation. These results indicate re‐exposure to cocaine cues induce gene‐specific mRNA expression via rapid changes in DNA methylation.Support or Funding InformationThis research was supported by NIH grants DA‐027115 and DA‐027525 (TEK) and DA024038 (KKS), as well as funding from and the W.M. Keck Foundation (TEK).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.