bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiac Conduction Disease in Huntington's Disease Mouse Model (BACHD)
Authors: Zhu Yujie , Shamblin Isaac , Ali Sameen , Gray Michelle , Huke Sabine 
Published: June 2021

ObjectiveHuntington's disease (HD) is a progressive neurodegenerative disease caused by a CAG repeat expansion in the gene encoding the huntingtin protein. In addition to the central nervous system, recent evidence indicates cardiac involvement in HD patients. ECG screening in HD patients suggested an increased prevalence of conduction abnormalities and compromised sinoatrial node (SAN) function. Here we tested if the huntingtin gene defect would cause increased arrhythmia susceptibility.MethodsWe used a conditional human huntingtin (HTT) Bacterial Artificial Chromosome (BACHD) transgenic mouse model at 8 months (motor dysfunction present) and 18+ months of age (advanced disease). Fibrosis level was assessed histologically. Surface ECG was measured in mice anesthetized with isoflurane and arrhythmia susceptibility was tested in response to sympathetic and parasympathetic agonists and their combination (autonomic conflict).ResultsIn 18+ month‐old mice overall cardiac structure was unremarkable. BACHD hearts were slightly larger, but HW/BW ratio was normal. Baseline ECG recordings showed prolonged QRS duration in BACHD mice. Stimulation with carbachol (parasympathetic agonist) resulted in increased premature atrial contractions (PACs), SAN exit block, tachy‐brady syndrome in BACHD mice. Stimulation with combined sympathetic and parasympathetic agonists (norepinephrine, epinephrine and carbachol) resulted in increased premature ventricular contractions, PACs, bigeminy and couplets in BACHD mice. Some of these events occurred also in younger BACHD mice, but to a lesser extent.Conclusions/Broader ImpactsThe BACHD mice showed signs of cardiac conduction system abnormalities and SA node dysfunction. This was observed in the absence of gross histological changes and during isoflurance anesthesia which dampened the influence of the autonomic nervous system. Stimulation with parasympathetic and sympathetic agonists uncovered increased atrial and ventricular arrhythmia susceptibility. Our study indicates that the huntingtin gene defect may cause progressive cardiac conduction system pathology that might increase the susceptibility to sudden cardiac death.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Alcoholic versus Non‐alcoholic Steatohepatitis: Levels of Expression of Some Proteins Involved in Tumorigenesis
Authors: Nguyen Luan , Masouminia Maryam , Mendoza Alejandro , Samadzadeh Sara , Tillman Brittany , French Barbara , French Samuel 
Published: June 2021

Non‐alcoholic steatohepatitis (NASH) is commonly associated with obesity, type 2 diabetes, and/or hypertriglyceridemia, while alcoholic steatohepatitis (ASH) is associated with alcohol abuse. Both NASH and ASH patients can develop cirrhosis and hepatocellular carcinoma if left untreated. However, the rate of tumorigenesis in NASH and ASH appears to be different. Individuals with NASH progress to cirrhosis at a rate of 7–10% annually, when individuals with ASH progress to cirrhosis at a rate of 10–20% annually. Thus, the objective of our study is to determine if there are differences in NASH versus ASH in the levels of different proteins expressed involved in cancer development. The method used was measuring the proteins expressed in liver biopsied sections from NASH and ASH patients using immunohistochemical staining with fluorescent antibodies and then quantitating the fluorescence intensity morphometrically. Normal liver biopsies were used as controls. The 20 proteins tested were parts of the Ingenuity Canonical Pathway of Molecular Mechanisms of Cancer and included: RAP2B, NAIP, FYN, PAK6, SUV39H1, GNAI1, BAX, E2F3, CKDN2B, BAK1, BCL2, DIABLO, RASGRF2, GNA15, PIK3CB, BRCA1, MAP2K1, BIRC3, CDK2, and ATM. For the results, in ASH, the proteins which had upregulated levels of expression were SUV39H1, E2F3, BCL2, BAK1, BIRC3, and GNAI1. In NASH, the proteins which had upregulated levels of expression were BAK1 and GNAI1 and the one which had downregulated levels of expression was BCL2. Additionally, the levels of expression for SUV39H1, E2F3, BCL2, BAK1, BIRC3 and GNAI1 were significant upregulated in ASH compared to NASH. These results showed significant differences in ASH compared to normal liver, and significant differences in ASH compared to NASH. We conclude that there are more proteins involved in tumorigenesis in ASH compared to NASH and normal liver, which is consistent with the known tumor development rate in ASH and NASH.Support or Funding InformationThis study was funded by NIH:NIAAA grant # UO1‐021898‐05This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
CXCR2 Regulates Hepatic Injury after Bile Duct Ligation by Altering Neutrophil Migration
Authors: Konishi Takanori , Schuster Rebecca , Lentsch Alex 
Published: June 2021

IntroductionCXC chemokines and their receptor, CXCR2, are important components for progression of hepatic inflammation. However, the contribution of CXCR2 for cholestatic liver injury have not been elucidated. Neutrophil recruitment in the liver and their releasing reactive oxygen species during cholestasis contribute to liver injury. In the current study, we sought to determine the role of CXCR2 in hepatic injury after bile duct ligation (BDL).MethodsWild‐type (WT) and CXCR2−/− mice were subjected to BDL to induce cholestatic liver injury. Serum and liver samples were obtained 14 days after BDL. Serum levels of alanine amino transferase (ALT) and liver myeloperoxidase content (MPO) were measured. Liver sections were stained with hematoxylin and eosin for assessing the extent of liver necrosis. Neutrophils in liver tissue was determined by immunonhistochemical staining for Ly‐6G.ResultsAfter BDL, CXCR2−/− mice had significantly lower serum ALT level and less necrotic area than WT mice. There was no difference in MPO level in the whole liver, however, the distribution of recruited neutrophils was different between WT and CXCR2−/− mice. In WT mice, neutrophils selectively accumulated to necrotic areas in liver parenchyma and infiltrated into the peri‐biliary lesions. In contrast, in CXCR2−/− mice, neutrophils were randomly scattered in the liver parenchyma, with less concentration of neutrophils in necrotic areas and peri‐biliary lesions.ConclusionThe data suggest that CXCR2 regulates liver injury after BDL by directing neutrophil migration to specific sites of hepatocyte and biliary cell injury.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Methodology to Determine Food Acquisition Strategies among Homeless Youth
Authors: Harris Cristen , Kloubec June 
Published: June 2021

BackgroundYouth represent a growing, and particularly vulnerable, subgroup of the homeless population in urban areas. Social service institutions, health care centers, and voluntary organizations have responded to this growth by creating a variety of programs to assist homeless youth in obtaining food, shelter, and medical care. Still, many of these individuals struggle each day to get the food they need. Only a handful of studies have examined the nutritional quality of meals available to homeless youth and how they obtain food. Lack of data is primarily due to the difficulty in studying this group due to their transiency and distrust of establishment figures.ObjectiveThe aim of this study is to create a method to describe how homeless youth access food and the nutritional quality and adequacy of food that they obtain.MethodsIn this cross‐sectional study, investigators orally administer a ~50‐item survey, adapted from published research, to homeless youth ages 14 to 24 in the greater Seattle/Tacoma area. Data collection takes place at multiple settings and organizations in which homeless youth access food. Individuals who meet inclusion criteria are invited to participate at these settings and are offered $10 at the completion of the survey. The survey asks information on general demographics; participants' current housing situation; factors relating to their ability to access food; and the kinds of food they acquire. Anonymity of participants is maintained by obtaining verbal assent rather than signed consent. All survey data is entered by researchers on site using REDCap™ software.SummaryCreating a method to gain a better understanding of how homeless youth obtain food and the nutritional quality of such food can help social services and nutrition programs improve the network of nutrition services and the quality of food available to this vulnerable population.Support or Funding InformationThis study was funded by a Bastyr University Faculty Student Research Grant (FSRG), award number H01A11.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 Assessment of Cognitive Food Consumption Experience
Authors: Atakan S. Sinem , Wansink Brian 
Published: June 2021

The goal of this research is to explore the cognitive experience of food consumption and develop a scale that can differentiate the various factors that individuals focus on while consuming food. Individuals differ in several aspects of the food consumption experience. Some pay more attention to the sensory aspects of the food whereas others focus on the quantity of the food or their surroundings. Currently, there are no reliable and valid instruments that assess the cognitive experience of food consumption.In‐depth interviews with consumers highlighted that, during food consumption episodes, consumers pay attention to the sensory tasting experience of the food, quantity consumed, and the nutritional content of the food. Furthermore, self‐monitoring (expectations and norms set by others who are readily present) and trying to eat healthy seem to be crucial aspects of the experience. Finally, distracted (non‐food related) thinking also emerges as part of the cognitive experience during consumption.Next, a survey study tested the dimensions that emerged from the in‐depth interviews. A pool of items for each dimension (attention to 1) the sensory experience, 2) quantity of food consumed, 3) nutritional content of the food, 4) healthy eating, 5) self‐monitoring, and 6) non‐food related thinking) was developed by the authors. Then, four professionals working on food consumption behavior were asked to review item content and question wording and to indicate any criteria that they believed were not adequately assessed. In addition, several consumers reviewed the scale questions for relevance and clarity. After making revisions based on feedback from both professionals and consumers, the questions were administered as part of a larger study that required consumers to consume several snack items. The participants (N = 56) were 18 years or older students at a large university. Exploratory factor analysis confirmed the six dimensions that emerged from the in‐depth interviews.This study is a preliminary exploration of the factors that shape the cognitive experience of food consumption. Future studies will focus on convergent, discriminant, and incremental validity of the newly devised scale.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Advocating the Responsible Use of Drugs through an Academic Service‐learning Activity in Higher Education.
Authors: Ignatova Tatiana , Yashchenko Oleksandre , Fernández Andrea , Sabaté Mar , Trullàs Eloi , Granados Victor , Morgó Judit , Solé Joel , Vacas Noemí , Vilaseca Jaume‐Elies , Garcia Maria Àngels , Cuffí Maria Laura 
Published: June 2021

Even with the great availability of new drugs and the best clinicians, therapeutic results are not always as expected. Poor therapeutic adherence leads to a waste of scientific knowledge and resources of the public health system. Medical students from the University of Barcelona analyzed this situation in their local hospital via a survey oriented to patients, which indicated a lack of adherence to prescribed treatments as well as an excess of self‐medication.A service‐learning activity begins with the identification of a real need and the preparation of an action plan (Kaye, 2004). The aim is to encourage best practices amongst the general public and health workers regarding drug consumption through an awareness campaign.In order to improve awareness and understanding of the consequences of the problem described, an audiovisual campaign was chosen, focusing on promoting therapeutic compliance and avoiding the risks of self‐medication. Thanks to the collaboration between the Medicine and Audiovisual degrees, two video clips were produced: (https://drive.google.com/open?id=0B1aCcXVIkA_cNDFseTNPb3Z2TUE) (https://drive.google.com/open?id=0B1aCcXVIkA_cV2t3bHdhQUpxdWc)This methodology improved the academic learning in Pharmacology and Audiovisual sciences as well as those related to other competencies required by our university.The skills acquired were generally assessed according to their specific degree competencies. The outcomes for the participants were: 1) learning to communicate scientific subjects in an appropriate language for the subject and audience, 2) detecting some common mistakes in drug prescription and/or therapeutic adherence, 3) producing audiovisual and multimedia content and 4) networking with experts from another field of knowledge.Kaye, C. B. The complete guide to service learning: Proven, practical ways to engage students in civic responsibility, academic curriculum, & social action. Free Spirit Publishing, 2004.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Clinical Potential of an Enzyme‐based Novel Therapy for Cocaine Overdose
Authors: Zheng Fang , Zhan Chang‐Guo 
Published: June 2021

It is a grand challenge to develop a truly effective medication for treatment of cocaine overdose. The current available, practical emergence treatment for cocaine overdose includes administration of a benzodiazepine anticonvulsant agent (e.g. diazepam) and/or physical cooling with an aim to relieve the symptoms. The inherent difficulties of antagonizing physiological effects of drugs in the central nervous system have led to exploring protein‐based pharmacokinetic approaches using biologics like vaccines, monoclonal antibodies, and enzymes. In particular, we have rationally designed and discovered highly efficient cocaine‐metabolizing enzymes for therapeutic treatment of cocaine overdose and addiction. However, none of the pharmacokinetic agents has demonstrated convincing preclinical evidence of clinical potential for drug overdose treatment without a question mark on the timing used in the animal models. In this investigation, we have made use of animal models, including locomotor activity, protection, and rescue experiments in rats, of drug toxicity treatment with clinically relevant timing for the first time. It has been demonstrated that an efficient cocaine‐metabolizing enzyme developed in our previous studies can rapidly reverse the cocaine toxicity whenever the enzyme is given to a living rat, demonstrating promising clinical potential of an enzyme‐based novel therapy for cocaine overdose as a successful example in comparison with the commonly used diazepam.Support or Funding InformationThis work was supported by an NIDA Translational Avant‐Garde Award (grant UH2/UH3 DA041115) and NIDA R01 grants (DA035552, DA032910, DA013930, and DA025100).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 Medial Prefrontal Cortex is Involved in Social Odor Recognition Memory
Authors: Granata Lauren M. , Robinson Siobhan , Hienz Robert D. , Davis Catherine M. 
Published: June 2021

ObjectiveThe medial prefrontal cortex (mPFC) is critical to mediating attention and social cognition, but its specific role in memory processing is unclear. In a rodent model of social odor recognition memory (SORM), we assessed the role of the prelimbic and infralimbic regions of the mPFC in social motivation and recognition memory at different stages of the memory process (encoding, consolidation, and retrieval). In the same animals, we also assessed the role of these subregions of the mPFC in sustained attention, using the rodent psychomotor vigilance test (rPVT).MethodsThe SORM task involves three phases (familiarization, habituation, and recognition), and requires olfactory‐based discrimination between familiar odors and novel odors from conspecifics, where failure to show preference for novel odors on the test phase indicates a memory deficit. The rPVT is a sustained attention test that measures accuracy, premature responding, and response times to the presence of a stimulus light that appears after a random waiting period between 3–10 seconds. Using pAAV‐hSyn‐hM4D(Gi)‐mCherry (“designer receptors,” DREADDs) injected bilaterally into the prelimbic or infralimbic regions of the mPFC, we remotely silenced these regions during behavioral testing via injections of the “designer drug,” clozapine‐N‐oxide (CNO).ResultsFor the SORM test, injecting CNO (1 mg/kg, i.p.) 30 minutes prior to the habituation phase did not impair novel odor discrimination on this phase, but did result in impaired memory for a novel odor on the recognition test day 24‐hrs later. These effects were not a function of CNO administration alone because the impairment was found on the drug‐free test day 24‐hrs after the previous CNO injection. In a second study, injections of CNO (0–5 mg/kg, i.p.) were administered 30‐min prior to different rPVT sessions. CNO at 1 mg/kg had effects on premature responding in the rPVT, without impairing response times.ConclusionsSilencing the prelimbic and infralimbic subregions of the mPFC impaired memory performance the recognition test phase of the SORM test, without inducing a motor impairment in the psychomotor vigilance test, indicating that the mPFC could be involved in encoding, and possibly consolidating, information about social odors acquired during habituation.Support or Funding InformationThis work was supported by a grant from NASA (NNX15AC71G) to CMD.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Determining Key Carbonic Anhydrase Isozymes Involved in Learning and Memory via Mouse Memory Assays
Authors: Lemon Nicole , Sanku Rajesh Kishore Kumar , Chong Anthony M. , Ilies Marc A. , Walker Ellen A. 
Published: June 2021

Carbonic anhydrase (CA) is a zinc enzyme that catalyzes the reversible reaction between carbon dioxide and bicarbonate. This reaction is important in many tissues and its functions include recycling and secretion of cerebrospinal fluid and pH homeostasis. In mammals, 16 isozymes have been described to date, with different catalytic activity, sub‐cellular localization, and tissue distribution. CA isozymes located in the CNS are believed to be involved in neuronal signaling and synaptic strengthening suggesting that activation of these isozymes may enhance learning. The role of CA in learning and memory processes is not fully elucidated, predominantly due the fact that most of the carbonic anhydrase activators (CAA) available today are either inefficient activators or may lack appropriate physicochemical properties to cross blood brain barrier. The purpose of the current study is to profile a set of lipophilic CA activators and to determine the important isozymes of CAs involved in learning and memory. Therefore, we designed and synthesized series of novel lipophilic CAAs with discreet activation profiles for different CA isozymes in the CNS. Our strategy is to selectively activate one, two, and/or three different isozymes with our discrete set of CA activators. In the current study, a series of novel CAAs were profiled using a mouse memory assay known as the Novel Object Recognition Test (NORT). Solubility and lipophilicity for each compound were also determined and compared along with the activation profiles (KA) of multiple isozymes for all compounds. Representatives with different activation profiles and optimal physicochemical properties were assessed for learning and memory in mice to identify the main CA isozymes likely involved in learning and memory. When tested in NORT, CAAs protected mice from scopolamine‐, ketamine‐, and acetazolamide‐induced recognition deficits when tested using doses of 0.03 mg/kg CAA, i.p. and a 30 min pretreatment. Considering both the physicochemical and activation profiles, preliminary results gathered by testing CAAs in NORT revealed that several CA isozymes present in the CNS are responsible for learning and memory. Moreover, our data suggest that CAAs protect retention from drug‐induced memory disruption without affecting the motor activity.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 Effects of HIV‐1 Gp120 on the Puncta Count and Expression of α5‐Containing GABAA Receptors in Cultured Rat Hippocampal Neurons
Authors: Jo Adrienne , Green Matthew , Thayer Stanley 
Published: June 2021

Approximately 50% of the >30 million people worldwide affected by human immunodeficiency virus‐1 (HIV‐1) suffer from cognitive impairments known as HIV‐1‐associated neurocognitive disorders (HAND). HIV‐1 can infect microglia, leading to the release of toxic proteins, such as envelope glycoprotein 120 (gp120IIIB), which causes neurotoxicity and synaptodendritic damage. Gp120 is known to induce the release of interleukin‐1β (IL‐1β), a cytokine released by microglia. Previous work shows that IL‐1β increases the function of α5‐containing GABAA receptors (α5‐GABAA‐Rs), which lowers cell excitability and may contribute to cognitive impairments. Thus, we tested whether gp120 would increase the expression of protein clusters of α5‐GABAA‐Rs in primary hippocampal cultures derived from embryonic day 17 Sprague Dawley® rats. Immunocytochemistry was performed to examine the localization of α5‐GABAA‐Rs relative to microtubule‐associated protein 2 (MAP2) immunoreactivity. Based on previous electrophysiology experiments on α5‐GABAA‐Rs, we hypothesize that gp120 increases α5 puncta. Preliminary data demonstrates that gp120 leads to a trending increase in α5 puncta, which might explain the increased neuronal inhibition and decreased cell excitability seen in vitro. Altered excitability may lead to the cognitive impairments found in HAND patients. Thus, inhibition of α5‐GABAA‐Rs may be a novel target for the treatment of HAND.Support or Funding InformationThis investigation was supported by DA07304 and the National Institute on Drug Abuse of the National Institutes of Health under Award Number 1R25DA039074‐01A1 through the Summer Research Program for Diversity Students in PharmacoNeuroImmunology (PNI) under Life Sciences Summer Undergraduate Research Programs.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.