bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiovascular Responses to Selected Cranial Osteopathic Manipulations in Hypertensive Patients
Authors: Ioudina Marina , Toder Eric , Muyot Aurelio , Salloum Liza , Boo Sue , Concepcion Jhaunden 
Published: June 2021

Background and PurposeOsteopathic cranial manipulations (CM) have been used as a part of therapeutic management of hypertensive patients. However, our knowledge about physiological responses to CM in cardiac patients is limited. A quantitative relationship between applied CM and cardiovascular parameters has not been well established. The purpose of this study was to measure changes in heart rate, autonomic input to the heart by using the heart rate variability test, cardiac contractility by using impedance cardiography, and systemic blood pressure in response to selected CM, namely occipital‐atlantal decompression, occipital‐mastoid decompression, and compression of the fourth ventricle.MethodHypertensive 65–75 year old subjects, three men and two women, were involved in this study. Hypertension was controlled by an angiotensin‐converting enzyme inhibitor (3 subjects), calcium channels blocker (1 subject) and beta‐blocker (1 subject). Each subject participated in the experimental (CM) and control (sham) groups. A non‐invasive impedance cardiography method was used to measure changes in cardiac parameters before and after manipulations. Data were recorded and analyzed using BIOPAC Systems, Inc. equipment and software. Blood pressure was measured before and after manipulations by using a sphygmomanometer. All manipulations were performed by the same osteopathic physician.ResultsCranial and sham manipulations resulted in different responses by the subjects. CM produced a decrease in systolic (5%) and mean arterial (6%) pressures, and revealed a trend towards an increase in sympathetic and decrease in parasympathetic cardiac activity based on heart rate variability test. Sham manipulations did not affect blood pressure and were associated with a trend towards a decrease in sympathetic and increase in parasympathetic cardiac activity. No changes in cardiac contractility were recorded for CM and sham manipulations.Discussion and conclusionIt appears that cranial manipulations may enhance the antihypertensive effect of medication through the effect on autonomic nervous system. The physiological effect of CM on autonomic control of systemic hemodynamics needs further investigation.Support or Funding InformationThis project was funded by the TUN Research Grant AwardThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Differences in cell proliferation in the cpk and Pkd1 mouse models of polycystic kidney disease
Authors: Rumschlag Matthew , Holthaus Conner , Ellis Monica , Swayze Emma , Zebolsky Aaron , Larson Erik , Heuvel Gregory Vanden 
Published: June 2021

Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common potentially fatal single gene disorders, resulting from mutations in either the Pkd1 or Pkd2 gene. Renal pathologies found in ADPKD include cysts resulting from increased fluid secretion, cell proliferation, and apoptosis, with an altered differentiation of the epithelial cells lining the cysts. In humans, ADPKD is thought to result from an inherited mutation in the PKD1 gene, followed by a somatic “second hit” mutation in the normal allele. The mechanism of this second hit is not understood. We analyzed the genomic sequence of human PKD1 and found extensive tandem repeats of guanine capable of supporting guanine quadruplex (G4) structures. G4 DNA is four‐stranded, and it is known to functionally contribute to recombination and mutagenesis. By comparison, mice do not carry extensive G4 repeats in the Pkd1 gene, thus targeted deletion of both Pkd1 alleles are required to generate cysts. However, homozygous Pkd1 null mice are embryonically lethal. Therefore, we have generated mice carrying a kidney specific deletion of the Pkd1 gene, called Pkd1CD. These mice develop rapid cystic disease and die by 14 days of age. Another commonly studied mouse model of PKD is a mutation in the cystin gene (cpk mice), which is a mouse model of ARPKD. These mice have a complete loss of the cystin gene, however, they survive until about three weeks of age. To begin to determine the differences in disease progression between the Pkd1CD mice and the cpk mice, we evaluated cell proliferation in these two models of PKD. While kidneys isolated from Pkd1CD mice showed high levels of cell proliferation in the cyst lining cells, similarly cystic kidneys from cpk mice showed very little cell proliferation in the cyst lining cells. Moreover, we observed differences between PCNA and Ki67 labeling as markers for cell proliferation in both mouse models. Because these mouse models differ significantly from human ADPKD, future studies will include replacing portions of the mouse PKD1 gene with the human PKD1 gene that includes the G4 repeats.Support or Funding InformationNIH DK100972This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Bifidobacterium grown on human milk oligosaccharides produce tryptophan metabolite Indole‐3‐lactic acid that significantly decreases inflammation in intestinal cells in vitro
Authors: Ehrlich Amy M , Henrick Bethany , Pacheco Alline , Taft Diana , Xu Gege , Huda Nazmul , Lozada‐Contreras Michelle , Goodson Michael , Slupsky Carolyn , Mills David , Raybould Helen 
Published: June 2021

Bifidobacterium longum subsp. infantis (B. infantis) is a commensal bacterium that colonizes the infant gastrointestinal tract. This bacterium can efficiently utilize the abundant supply of oligosaccharides found in human milk (HMO) to help establish residence and generate bioactive metabolites which may produce beneficial effects by acting directly on the host. We hypothesized that metabolites from Bifidobacterium grown on human milk oligosaccharides would reduce inflammation in the intestine. To test this we first needed to identify metabolite candidates by growing B. infantis on either lactose or HMO and analyzing the metabolites produced using NMR spectroscopy. These metabolites were then compared to those found in Bifidobacterium‐dominated infant fecal samples. Once specific metabolites were identified, we treated intestinal and macrophage cells grown in culture to test if they exhibited an anti‐inflammatory response during endotoxin challenge. Lastly, we sought to find which pathway might be activated. We found that B. infantis grown on HMO produced significantly greater quantities of the tryptophan metabolite indole‐3‐lactic acid (ILA). Significantly higher amounts of ILA were also found in fecal samples from a population of infants with high compared to low abundance of Bifidobacterium species. The direct effects of ILA were assessed in macrophage and intestinal epithelial cell lines. ILA (at concentrations from 1 to 10mM) significantly attenuated lipopolysaccharide (LPS)‐induced activation of NF‐kB in macrophages. Similarly, ILA significantly attenuated LPS‐induced increase in the pro‐inflammatory cytokine IL‐8. ILA acts through the aryl hydrogen receptor (AhR) in intestinal epithelial cells as shown through increased nuclear localization of the AhR as well as increased protein expression of the AhR targeted gene CYP1A1. Activation of the AhR has been shown to exert a multitude of beneficial effects on the host including promoting normal intestinal immune function. These findings suggest that ILA, a predominant metabolite from B. infantis, can protect the epithelium via activation of AhRThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Preventive effects of medium‐chain triglycerides supplementation on the dysfunction of mitochondrial oxidative phosphorylation in skeletal muscle under cachectic condition
Authors: Hirabayashi Takumi , Tanaka Minoru , Matsumoto Tomohiro , Ikeji Takuya , Ono Kohei , Takuwa Miho , Maeshige Noriaki , Kondo Hiroyo , Fujino Hidemi 
Published: June 2021

Cachexia is a complex metabolic syndrome associated with underlying chronic diseases and is characterized dysfunction of mitochondrial oxidative phosphorylation in skeletal muscle. The preventive effects of medium‐chain triglycerides (MCT) supplementation on the dysfunction of mitochondrial oxidative phosphorylation in skeletal muscle under cachectic condition have been investigated in the present study. ICR mice were randomly divided into 4 groups; control, lipopolysaccharide (LPS), LPS plus long‐chain triglycerides (LCT), LPS plus MCT supplementation. LCT and MCT oil (The Nisshin OilliO Group, Ltd, Tokyo, Japan) were administered to the LPS+LCT and LPS+MCT groups orally by a catheter for 1 week. Cachexia was induced in the LPS, LPS+LCT and LPS+MCT groups via LPS injection (7.5 mg/kg body weight, i.p.) after the supplementation. LPS resulted in a decrease in succinate dehydrogenase (SDH) activity, which is an indicator of mitochondrial function, and PGC‐1α, which is an indicator of mitochondrial biogenesis, in tibialis anterior muscles. LPS also induced a reduction of total ketone bodies concentration level in blood plasma. Meanwhile, MCT supplementation suppressed the decrease of SDH activity and total ketone bodies concentration. In addition, MCT supplementation increased the level of citrate synthase activity in the muscles. These results suggested that MCT supplementation could prevent dysfunction of mitochondrial oxidative phosphorylation in skeletal muscle under cachectic condition.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Molecular Transducers of Physical Activity Consortium (MoTrPAC): Creating a Comprehensive Map of Molecular Changes in Response to Physical Activity
Authors: Williams John P. , Joseph Lyndon ,   the MoTrPAC Consortium
Published: June 2021

The NIH Common Fund initiated the Molecular Transducers of Physical Activity Consortium (MoTrPAC) in December 2016 by issuing 19 grants to 37 Principal Investigators from 23 institutions.Aim 1MoTrPAC will assemble a comprehensive map of the molecular changes that occur in response to exercise and provide insights into how they are altered by age, sex, body composition, and fitness level.Aim 2To fulfill its overall objective of facilitating investigator‐initiated studies and catalyzing the field of physical activity research, MoTrPAC will develop a user‐friendly database that any researcher can access to develop hypotheses regarding the mechanisms whereby physical activity improves or preserves health.SummaryWe provide an update on the progress and overview of the study design to be employed by MoTrPAC to develop a molecular map of signals that are involved in transmitting the tissue‐specific and systemic effects of physical activity in animals and humans.Support or Funding InformationNIH Common FundThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Profiling the Post‐Injury Hippocampal MicroRNA Response to Transient Forebrain Ischemia: Sub‐regional Differences Between Cornu Ammonis‐1 and Dentate Gyrus
Authors: Arvola Oiva Jouko , Kaidonis Georgia , Xu Lijun , Griffiths Brian , Stary Creed 
Published: June 2021

ObjectivesEven brief periods of ischemia can result in delayed neuronal cell death in hippocampal cornu ammonis‐1 (CA1), resulting in impaired memory and learning, whereas neurons in the adjacent dentate gyrus (DG) are relatively ischemia resistant. Understanding the pathophysiological and molecular mechanisms underpinning the selective ischemic vulnerability of the CA1 may translate to novel clinical interventions improving outcome in survivors of cerebral ischemia. MicroRNAs (miRNAs) are short (~18–25 nucleotides long) non‐coding RNAs that modulate translation of target messenger RNAs. To date, the miRNA expression profiles of hippocampal CA1 and DG sub‐regions in response to forebrain ischemia have not been examined. The objective of the present study was to assess and compare post‐injury miRNA expression patterns between CA1 and DG in a rat model of forebrain ischemia.MethodsAll experiments were conducted in conformance with the FASEB Statement of Principles for the use of Animals in Research and Education. CA1 and DG sub‐regions were dissected from rat hippocampi following a 10‐minute forebrain ischemia at 3 time points (3h, 24h, and 48h) and at baseline. Total RNA was extracted from samples using Quick‐RNA™ MiniPrep kits (Zymo Research), and the expression of 423 miRNAs were analyzed using nCounter® miRNA expression panel (NanoString). Successful sub‐regional dissection was validated using RT‐qPCR detection of the DG‐rich gene desmoplakin.ResultsPronounced differences between CA1 and DG in miRNA expression was observed for several miRNAs, greatest with mir‐329, mir‐219‐2‐3p and mir‐181a, known regulators of ischemic injury. Relative levels of CA1 and DG miRNA expression were greatest in established brain‐enriched miRNAs, including mir‐124.ConclusionsMiRNA expression profiles in response to transient forebrain ischemia were assessed and compared between hippocampal sub‐regions for the first time. Observed differences in microRNA expression patterns between CA1 and DG may explain selective CA1 ischemic vulnerability. Targeted modulation of select miRNAs identified here may serve as a therapeutic intervention to improve cognition in survivors of cerebral ischemia.Support or Funding InformationSupported by Finnish Cultural Foundation award to Dr. Arvola and American Heart Association award 14FTF19970029 to Dr. Stary.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Have Some Tea, Feed Your Brain: How EGCG Acts as a Protective Agent in a Parkinsonian Model
Authors: Blackburn Josephine Cetha , Magness Emily , Roberts James L 
Published: June 2021

Ferrous iron is important in biological function but can be oxidized into ferric iron, at which point it causes oxidative stress. Ferric iron accumulation leading to oxidative stress is one of the factors that contributes to forms of dementia including that associated with Parkinson's Disease. A compound found in green tea called Epigallocatechin Gallate (EGCG) had been shown to act as a metal chelating factor and can naturally bypass the blood brain barrier. Using EGCG as a potential protective agent against Parkinson's disease development would provide a solution to issues regarding drug administration to the brain. We hypothesize that introducing EGCG to the media will help to prevent the oxidation of naturally occurring iron and prevent oxidative stress, leading to less cell death. In this study we used N27 dopaminergic neurons treated with 6‐ Hydroxydopamine (6OHDA) as a model for Parkinson's disease development. In the 6OHDA model for Parkinson's disease, DMT1, one of the proteins responsible for iron uptake, is upregulated increasing iron influx and stimulating oxidative stress. Prior to exposing the cell cultures to 6OHDA, varying concentrations of EGCG were introduced to determine protectiveness. We determined that the IC50 of 6OHDA (normally 35μM) was increased to 45μM upon protection with 5μM of EGCG, 50μM upon protection with 10μM of EGCG, and 55μM upon protection with 20μM of EGCG. This indicates that EGCG is protective in this Parkinsonian model and could possibly have health benefits in the diet. We are currently conducting experiments to determine how EGCG is preventing oxidative stress in this model.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Development of a Cell Culture System to Examine the Acclimation, Contraction, and Cytoskeletal Remodeling of A7r5 Smooth Muscle Cells to Microgravity
Authors: Whitenack Kaylee M , Arnold Callie , Gibson Danielle , Fultz Michael 
Published: June 2021

Few studies have examined the acclimation and contraction of smooth muscle cells in microgravity. In addition, the cytoskeleton in smooth muscle has not been thoroughly examined habituated to microgravity. Although previous studies have noted that the phenotype of smooth muscle may be gravity dependent, those that have been performed have utilized simulated microgravity. The cytoskeleton has been implicated by several investigators as allowing single cells in vitro to respond to changes in gravity and may serve as a gravity sensor (reviewed in Vorselen et al., 2016) at the individual cell level. This investigation will focus on the effect of microgravity on the alpha‐actin, beta‐actin, and myosin components of the cytoskeleton in resting and contracting A7r5 smooth muscle cells. We have provided evidence of differential remodeling of the alpha‐actin, beta‐actin, and myosin cytoskeletal domains in smooth muscle (Brown et al., 2006, Li et al., 2001, Fultz et al., 2000, Fultz and Wright, 2003, and Thatcher et al., 2011). At rest these are organized into filamentous stress cables that run the length of the cell. Upon stimulation, α‐actin and myosin interact to produce force that results in shorting of the cell. This shortening applies stress on the beta‐actin filaments which then undergo subsequent remodeling into configuration that holds the cell in the shortened state. Alpha‐actin and myosin then undergo disassembly/reassembly into a configuration that is optimized for further contraction and aggregate into podosomes that appear as column‐like structures in the contracted cell. While we have proposed that this remodeling is essential mechanism in the development and maintenance of force in smooth muscle (Li et al., 2001). Others have proposed that pododome formation may be relevant in the invasiveness of smooth muscle that is observed in cardiovascular disease as podosomes formation correlates with cell motility and localized degradation of the extracellular matrix (Burgstaller and Gimona, 2005; Lener et al., 2006; Murphy and Courtneidge, 2011). In collaboration with SpaceTango (Lexington, KY) and the Craft Academy for Excellence in Science and Mathematics at Morehead State University, a cell culture system has been developed that will allow for the culture, visualization, stimulation, and subsequent fixation of A7r5 cells aboard the International Space Station. Upon return to Earth, components of the cytoskeleton will be examined by fluorescent microscopy to investigate if microgravity alters the characteristic remodeling observed on Earth.Support or Funding InformationThis material is based upon work supported by NASA Kentucky under NASA award No: NNX15AR69H.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Electrical field stimulation‐induced vasorelaxation responses decreased in anterior and middle cerebral arteries of endotoxemic rats
Authors: SOYDAN GURAY 
Published: June 2021

IntroductionEndotoxic shock is characterized by vascular dysfunction, hypotension and multiple organ dysfunction. Loss of vascular tone is a key factor responsible for death in endotoxic shock. Perivascular innervation has an important role in the regulation of vascular tone. Neural control of the arteries is mediated by adrenergic and nitrergic neurons. The nitrergic component is dominant in brain arteries while adrenergic component is dominant in mesenteric arteries. Lipopolysaccharide (LPS) alters the electrical field stimulation (EFS) responses in mesenteric arteries in vitro. Our aim is to study the alterations of EFS responses of cerebral and mesenteric arteries in endotoxemia in rats.Material and MethodsLPS (10 mg/kg) were given intraperitoneally to rats to make an animal model os sepsis. Rats were anesthetized with gaseous carbon dioxide and decapitated 20 hours after injection, Basilar, anterior cerebral, middle cerebral and 3rd branch of mesenteric arteries were isolated and mounted in a wire myograph covered with platinum electrodes. After U46619 precontraction, frequency‐dependent EFS responses were obtained using a constant current stimulator.ResultsHigh K+ responses did not change in brain and peripheral arteries. EFS‐dependent vasorelaxation responses decreased in anterior and middle cerebral arteries in endotoxemic rats. EFS‐induced vasorelaxation responses of basilar artery and vasoconstriction responses of mesenteric arteries did not change in endotoxemic rats.ConclusionsIn this study we demonstrate for the first time that EFS‐induced vasorelaxation responses of some cerebral arteries decreased in endotoxemic rats. This EFS‐dependent alterations could be explained by degeneration of perivascular innervations or an imbalance between adrenergic and nitrergic neurons.Support or Funding InformationThis study was funded by Hacettepe University Scientific Research Projects Coordination Unit (TSA‐2017‐12848).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The Evolution of Heterocomplexation and Multifunctionality in the S100 Protein Complex Calprotectin
Authors: Harman Joseph , Loes Andrea , Shi Ran , Heaphy Maureen , Harms Michael 
Published: June 2021

Calprotectin is a multifunctional complex of S100 proteins A8 and A9. It promotes neutrophil migration to sites of inflammation, kills bacteria via oxidative bursting and transition metal sequestration, and exacerbates the inflammatory response by stimulating proinflammatory cell surface receptors. This extensive multifunctionality is the product of preferential heterocomplex formation between A8 and A9, as individual A8 or A9 homodimers are insufficient to perform all of these functions. Our research aims to understand how modern A8 and A9 proteins evolved from a shared homomeric ancestor to form the highly multifunctional calprotectin complex. When did A8/A9 heterocomplexation evolve? How have key biophysical differences between A8 and A9 homo‐ and heterocomplexes changed over time? What are the functional consequences of evolving preferential heterocomplexation? To answer these questions, we are examining complex formation between both extant and ancestrally reconstructed A8 and A9 proteins. We are also characterizing the biophysics of preferential heterocomplexation by measuring oligomeric state and proteolytic susceptibility for all members of the calgranulin clade (S100 proteins A8, A9, A12, and MRP126). Finally, we are mapping changes in biophysical properties and complex formation to changes in functionality. We have found that all therian A8s and A9s form proteolytically resistant heterocomplexes, while the ancestor of all calgranulins forms a proteolytically resistant homohexamer. Antimicrobial activity appears to be conserved across extant A8/A9 complexes, and we are currently evaluating this functionality for ancestral complexes. This work will help unravel the evolution of key biophysical features that contributed to the evolution of multifunctionality in this important innate immunity protein complex.Support or Funding InformationThis work was funded by the National Institutes of Health (NIH‐T32GM007413). Michael J. Harms is a Pew Scholar in the Biomedical Sciences, supported by The Pew Charitable Trusts.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.