bluuebunny/crossref_metadata_2025_split huggingface dataset:
PrPc: The Normal Prion
Authors: Wright Collette , Howard Ashley , Lim Shulammite , Lakshman Priya , Loo Cheyenne 
Published: June 2021

PrPc is a normal cell‐surface glycoprotein that is conformationally characterized by two alpha helices and two complex‐type N‐linked oligosaccharide chains. This protein is unique in its propensity to misfold into a neurodegenerative disease‐causing proteinaceous infectious particle, known as a prion. PrPc can undergo conversion into PrPSc through spontaneous misfolding, a genetic mutation of the human PRNP gene, or exposure to a prion from an external source. When this happens, its composition shifts from an alpha‐helical, soluble protein low in beta pleated sheets to an insoluble, protease‐resistant particle with a high percentage of beta sheets. This resulting misfolded form, known formally as PrPSc, is pathogenic and aggregates in neural tissue by recruiting and converting more PrPc to PrPSc, ultimately causing neuronal cell dysfunction followed by cell death. The prion's form of “self‐replication” without utilizing genetic material is particularly fascinating, as it appears to defy the central dogma of biology and differs from all other pathogenic particle infection mechanisms. It is notable that some prions have evolved to act as transmissible infectious agents, similar to viruses, despite the absence of genetic material. This distinguishes some prion diseases, such as chronic wasting disease (CWD) and scrapie, from their inherited disease counterparts. The biosynthesis pathway of PrPc is similar to other cellular proteins, with replication occurring on the ribosomes on the endoplasmic reticulum. However, whereas malfunctioning proteins are normally tagged by ubiquitin and then degraded in a proteasome, the ubiquitin‐proteasome complex is inhibited during prion formation, allowing PrPSc to form and survive degradation, leading to its buildup in cytosol and subsequent neurotoxicity. Human and animal prion diseases have been classified into three broad categories‐‐genetic, sporadic, and acquired‐‐based on properties of the PrP proteins and prion infection morphology. Physical symptoms of prion infection include deviant behavior, dementia, ataxia, insomnia, paraplegia, and paresthesias. Commonly discussed prion‐induced diseases (differentiated via host type and slight conformational discrepancies between misfolded proteins) include scrapie, kuru, CJD, bovine spongiform encephalopathy (mad cow disease), and CWD. Here, we present current research on prions, with a focus on CWD, which was first found in Colorado and affects deer and other cervids.The Olathe North High School Team 1 MSOE Center for BioMolecular Modeling SMART Team used 3‐D modeling and printing technology to examine the structure‐function relationships and histology of PrPc, or the normal cellular prion.Support or Funding InformationThis project is a joint venture between the Milwaukee School of Engineering and the Medical Professions Academy.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 Role of the Furin‐Cleavable Linker and KDEL Sequence in Cytotoxicity of Recombinant ImmunoDNase
Authors: Baker Jillian 
Published: June 2021

The lack of specificity of standard chemotherapies to identify and kill cancer cells has challenged researchers to engineer targeted therapies to replace conventional treatments. One strategy that is currently being optimized to treat cancer is the use of recombinant immunotoxins (RITs). RITs are chimeric proteins that are engineered to contain an antibody conjugated to a toxin. The antibody allows for specific targeting of cancer cells while the toxin domain is internalized by the targeted cell and subsequently induces cell death. These therapies suffer from several problems, including non‐specific toxicities, low anti‐tumor activity, and immunogenicity. A bacterial moiety introduced into a patient with an intact immune system can elicit an immune response that consequently eliminates the possibility of retreatment. Deimmunized, humanized, and fully human immunoconjugates have been engineered, but often lack efficacy. We are using specific sequences known to assist cellular intoxication by Pseudomonas exotoxin A (PE) to enhance the activity of human‐derived immunotoxins. We are developing a recombinant immunotoxin based on human DNase I, using a furin‐cleavable linker and KDEL ER retention sequence adapted from the PE intoxication strategy. We expect this construct to have low immunogenicity, high specificity for dividing cells, and enhanced toxicity relative to the unmodified DNase I construct.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Expression profile of adiponectin and adiponectin receptors in high fat diet feeding chicken
Authors: Lin YuanYu , Ding ShihTorng 
Published: June 2021

Adiponectin is a circulatory cytokine secret from adipose tissue and exerts critical metabolic function in mammals. Avian also expressed adiponectin and adiponectin receptors in peripheral tissues, whereas the expression profiles are very different from mammals and the role of its unique profile is still unknown. The current study explore the role of adiponectin and adiponectin receptors in chicken by high‐fat diet feeding. Twenty Taiwan L2 chickens were challenge with 10% high‐fat diet for 6 weeks. The results are showed that body weight, plasma triglyceride, plasma cholesterol and DPP4 were increased by high‐fat diet treatment. Interestingly, we first demonstrated that chicken macroadiponectin and DsbA‐L (adiponectin multimerization enzyme) were elevated by high‐fat diet feeding. Moreover, the mRNA expression of adiponectin and adiponectin receptors were increased in fat tissues by high‐fat diet treatment. For metabolic‐related genes analysis, FAS, ATGL, LPL and PPAR γ were increased in high‐fat diet group. These results were suggested that high‐fat diet treatment may alter the expression profiles of adiponectin and metabolic genes in chicken fat tissue. In sum, we explore the effect of high‐fat diet in expression profile of adiponectin and its receptors in chicken and provide the new insights for how adipokines modulate physiological function in avian species.Support or Funding InformationThe authors would like to express our gratitude to the laboratory members for their help and input during this study.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Perilipin 5 Protein‐Protein Interactions
Authors: Hughes Erin K. , Tansey John T. 
Published: June 2021

Type II diabetes mellitus and non‐alcoholic fatty liver disease are two examples of metabolic diseases that are reaching epidemic proportions in the US. Key to understanding these diseases and their progression is an understanding of neutral lipid metabolism. Perilipins are a class of five conserved proteins that are key regulators of lipid metabolism and are potentially involved in lipid trafficking within cells. The most recently discovered member of the family is perilipin 5, which is expressed most strongly in tissues that are highly oxidative such as heart, oxidative muscle, and fasting liver. Perilipin 5 is predominantly located on the surface of lipid storage droplets, but has also been found in the cytoplasm, nucleus, and the endoplasmic reticulum and mitochondria. We hypothesized that perilipin 5 moves between these cellular pools via interactions with other proteins. Furthermore, we hypothesized that interactions with Rabs were necessary for this trafficking to occur. CHO cells expressing perilipin 5 were assayed using western blotting and were found to express Rab 18. Immunoprecipitations are being used to assay for interactions between perilipin 5, Rab 18, and other proteins. Collectively these data will provide a more detailed picture of perilipin 5 in the cell.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
A novel assay to measure scrambling of natural phospholipids in reconstituted proteoliposomes
Authors: Wang Lei , Pandey Kalpana , Ploier Birgit , Menon Anant K. , Bütikofer Peter 
Published: June 2021

Scramblases transport phospholipids between the leaflets of a membrane bilayer in an ATP‐independent and bidirectional way to facilitate membrane growth and maintain lipid homeostasis. Members of two protein families, Class A G protein‐coupled receptors and the TMEM16 family of ion channels, have been identified to act as scramblases. However, the mechanisms by which they translocate phospholipids are still poorly understood. Synthetic glycerophospholipid analogs carrying fluorescent nitrobenzoxadiazole (NBD) groups, such as NBD‐phosphatidylcholine (NBD‐PC), have proven useful to identify and characterize phospholipid scramblases in membrane preparations and reconstituted proteoliposomes.We now have established a novel biochemical assay to measure the activity of scramblase proteins using radiolabeled natural phosphatidylinositol ([3H]PI) as probe. As sources of scramblase activity we used crude extracts from yeast containing ER membrane proteins, and also purified bovine opsin. We reconstituted symmetric large unilamellar liposomes containing trace amounts of [3H]PI. Addition of PI‐specific phospholipase C (PI‐PLC) resulted in hydrolysis of 46–52% of [3H]PI, i.e. the portion present in the outer leaflet of the bilayer. The time to reach maximal [3H]PI hydrolysis depended on the amount of PI‐PLC used. In contrast, PI‐PLC treatment of [3H]PI‐containing liposomes reconstituted with yeast extract containing scramblase activity or purified opsin resulted in protein‐dependent hydrolysis of 60–80% of [3H]PI, indicating that the [3H]PI located in the inner leaflet of the proteoliposomes became accessible to cleavage by PI‐PLC during the course of the experiment.To allow direct comparison of opsin's ability to scramble [3H]PI and NBD‐PC, we then prepared opsin proteoliposomes containing both [3H]PI and NBD‐PC and measured scrambling using PI‐PLC and dithionite, respectively, as probes. The results showed that opsin readily scrambled both NBD‐PC and [3H]PI, albeit with different characteristics. The results of these experiments, as well as experiments that directly compare opsin‐mediated scrambling of NBD‐PI and [3H]PI will be presented.apoproteinSupport or Funding InformationThis research is supported by the Velux StiftungThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Diltiazem Improves Twitch Tension in Dysferlin‐Null BLAJ Mice but Does Not Reduce Contraction‐Induced Muscle Damage In Vivo
Authors: Roche Joseph A. , Begam Morium , Collier Alyssa F. 
Published: June 2021

BackgroundThe L‐type Ca2+ channel blocker diltiazem (DTZ) protects dysferlin‐null A/J mice from muscle damage induced by large‐strain eccentric contractions (20 repetitions) (1). One of the disadvantages of studying the A/J mouse strain is that, it does not have a true control mouse strain. Additionally, A/J mice carry several non‐dysferlin mutations that might have an effect on muscle function (2). BLAJ mice, which carry the same dysferlin mutation as A/J mice, albeit in the C57BL/6J background, show lesser muscle damage than A/J mice after large‐strain eccentric contractions (3). We therefore developed a new model of eccentric exercise (40 repetitions of medium‐strain eccentric contractions) that reliably induces sufficient damage in BLAJ mouse muscle, in order to test if DTZ blocks contraction‐induced muscle damage in BLAJ mice.MethodsWe studied the tibialis anterior (TA) muscle in 3–4 month old, male, dysferlin‐null BLAJ mice. We measured contractile torque and exposed the TA muscle to eccentric contractions (one bout; 40 repetitions; 90–160 □ plantarflexion superimposed on maximal tetany of ankle dorsiflexors) with a custom‐built dynamometer. For one group of mice (Vehichle, VEH, N = 6 mice), we gave intraperitoneal injections of distilled water, once daily, for one week prior to eccentric contractions and three days thereafter (10 ul per gram body weight). For another group of mice (DTZ, N = 6 mice), we gave intraperitoneal injections of DTZ (72 mg/kg/day), once daily, following a similar injection schedule as the VEH group (we dissolved 72 mg DTZ in 10 ml distilled water and injected 10 ul per gram body weight). We assessed baseline contractile torque, torque changes after eccentric contractions, and histology of unexercised and exercised TA muscles.ResultsData are summarized in Table 1. DTZ improved Peak Twitch Torque, but did not provide protection against muscle damage from eccentric contractions.ConclusionDiltiazem might not offer protection against all types of contraction‐induced damage to dysferlin‐null muscle.Translational RelevanceDiltiazem might not be able to protect muscles in patients with dysferlin deficiency if muscle damage exceeds a certain threshold level.Support or Funding InformationThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Role of Tumor Necrosis Factor‐Alpha in Rheumatoid Arthritis
Authors: Link Tina , Kepner Alisa , Coruso Olivia , Dilip Megha , Jacobson Reagan , Stanovski Lisa 
Published: June 2021

Tumor necrosis factor‐alpha (TNF‐α) is a 233 amino acid, 17 kilodalton, homotrimer, bell‐shaped proinflammatory cytokine. TNF‐α is usually secreted from monocytes and macrophages and is also an inducer of many proinflammatory cytokines like IL‐1, IL‐6 and others to help regulate immune cell function. . TNF‐α has two transmembrane cell receptors, TNF‐R1 and TNF‐R2, which have functional binding domains located on the outside of the cell and catalytic signaling domains located inside the cell. TNF‐R1 mediates the activation of a number of transcription factors resulting in an increased inflammatory response, while TNF‐R2 increases the number of T‐cells through a proliferation/survival pathway. A high amount of TNF‐α compared to a low number of its receptors leads to joint inflammation and eventual shock, while a low amount of TNF‐α leads to cachexia. Rheumatoid Arthritis (RA) has many causes including environmental factors, proclivity of smoking, or a genetic history, but in all cases, TNF‐α seems to play a role in disease progression due to its high proteins concentration in advanced disease stages. The source of TNF‐α in joints could be due to the production of the protein by CD4+ T cells in the synovial fluid which has been associated with synoviocyte proliferation, osteoclast activation, and cartilage degradation. Attempts to inhibit TNF‐α are currently centered around general suppression of the protein through TNF‐α inhibitors, but due to the devastating effects these treatments have on the immune system, further studies are considering creating higher numbers of anti‐inflammatory cytokines to create a balance between inflammatory and anti‐inflammatory cytokines, while other studies are attempting to target downstream protein targets of TNF‐α in an attempt to selectively suppress disease symptoms. The Walton High School SMART Team has designed a 3D model of TNF‐α using JMOL to investigate the relationship between structure and function.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Curcumin Suppresses Pro‐Inflammatory Response through Interference of NF‐κB Activation in Human Umbilical Vein Endothelial Cells
Authors: Cheng An‐Chin , Yu Ya‐Mei , Chang Weng‐Cheng 
Published: June 2021

Oxidative stress and redox‐sensitive transcription factors are involved in the process of inflammation which plays a central role in the pathophysiology of atherosclerosis. NF‐κB is a redox‐sensitive transcription factor which was activated secondary to excessive mitochondrial ROS production in the endothelium, participating in a various of proinflammatory and prothrombotic reactions in the endothelial cells. In the present study, we found that the production of ROS was induced by IL‐1 β and pretreatment with curcumin could decrease the induction of ROS by IL‐1 β in human umbilical vein endothelial cells (HUVECs). Since atherosclerosis is a chronic inflammatory disease associated with increased oxidative stress in the vascular endothelium, we proposed that the inhibitory effect of curcumin on NF‐κB activation may be due to its antioxidant and anti‐inflammatory properties. We also measured the nuclear translocation of p65 and p50 protein of the NF‐κB family to examined whether the inhibitory effect of curcumin on the cytokine‐induced expression of pro‐inflammatory response is medicated via NF‐κB. Our results indicated that the nuclear translocation of p65 and p50 were induced by IL‐1 β, whereas the pretreatment with curcumin could inhibit the induction of translocation by IL‐1 β in HUVECs. Therefore, we confirmed that curcumin has an anti‐inflammatory effect through the partial interference of NF‐κB activation.Support or Funding InformationThis study was supported by NSC 100‐2313‐B‐309‐003 to A‐C Cheng and NSC 95‐2815‐C‐039‐019‐B to Y‐M Yu.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 LOW LEVEL LIGHT THERAPY, DIET, EXERCISE AND MEDITATION AS COMBINATION TREATMENT MODALITIES FOR TREATMENT OF FIBROMYALGIA
Authors: Labrousse‐Walker Lynn , Einstein George P. , Tulp Orien L. 
Published: June 2021

ObjectiveFibromyalgia is a systematic, “holistic” disease that impairs those it attacks at virtually all levels, including physically, mentally, and emotional. The goal of this study is to help determine any possible benefits or effects of Low level light therapy [LLLT] in combination with traditional treatments in reducing the widespread pain associated with fibromyalgia as described by the 1990 criteria classification as set by the American College of Rheumatology [ACR]. Fibromyalgia is thereby described as widespread musculoskeletal pain with 11–18 tender points. Other signs and symptoms may include, but not limited to fatigue, morning stiffness, disordered sleep and “fibro fog”. Studies show positive results on the use of LLLT in dental procedures, tendon ruptures and muscle fatigue, resulting in reduced pain. It is also theorized that LLLT helps reduce pain related to musculoskeletal and myofascial pain as it relates to Fibromyalgia.MethodsFifteen participants diagnosed with fibromyalgia via ACR criterion underwent combined treatment that included: Low level laser therapy, an alkaline‐rich diet, evening meditation, and 20 minutes of aerobic and strength exercises daily. Subjects were then administered 20‐minute Low Level Light Therapy sessions for six additional weeks. Each subject had palpatory examinations as described by the 1990 criteria classifications as set by the ACR to determine areas of widespread points of tenderness throughout the study to assist in determining the possible sites and effectiveness of LLLT administration. The palpatory examinations for points of tenderness were conducted before and throughout the sessions of LLLT treatment. Pain analog scales were used to assess the subjects' severity of pain at the start of each session. Diagrams of the 18 tender points as illustrated by the 1990 ACR classification criteria were completed by the participant before, during, and after the LLLT therapy was administered. The participants also consumed an alkaline‐rich diet throughout the study, and the first morning urine pH was reported daily to monitor dietary compliance. Furthermore, the subjects were engaged in exercise program and nightly meditation throughout the study.ResultsResults of the combined therapy show that the number of affected tender points diminished following LLLT throughout the study regardless of age; pain decreased linearly as time passed during treatment, sleep improved relative to time after time ‐ patients reported sleeping for longer periods of time as their pain intensity index decreased. The results of this study indicated that LLLT may be an effective adjunct to conventional treatments for fibromyalgia.Support or Funding InformationSupported by Institutional Resoures of USAT Montserrat and the Einstein Institute, NPB, FLThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Evaluating Approaches to Analyze Tissue Score Data
Authors: Meyerholz David , Beck Amanda 
Published: June 2021

Histopathology remains an important source of data in the clinical and research settings. However, qualitative evaluation of tissues alone has limitations for translational studies. Recent petitions for enhanced reproducibility in scientific studies have elevated the roles for scoring (semiquantitative and quantitative) of tissues. Effective tissue scoring requires appropriate statistical analysis to validate the group comparisons. Choice of appropriate statistical test is greatly influenced by experimental design (e.g. paired, unpaired, parametric, nonparametric, longitudinal, repeated measures, and multi‐factorial to name a few). We evaluated how the type of statistical analysis could impart highly skewed interpretations of the data. We evaluated mock tissue scores for inflammation representing two groups of tissues. For these ordinal scores, we analyzed the data (n=5/gp) using 4 statistical tests that have been used in the literature for comparing two groups of tissue date: paired T‐test, unpaired T‐test, Mann‐Whitney test and Kolmogorov‐Smirnov test. From these tests, the data produce a wide range of P values of 0.0161, 0.1823, 0.3175, and 0.5238, respectively. The data was further analyzed as to what type of test should have been run to be valid. The data (generated by rolling of dice) failed a normality test (P<0.05, Shapiro‐Wilk test) and given ordinal scoring approach – data analysis should have focused on non‐parametric approaches that showed no significance. Statistical tests that give the best “confidence” in the data interpretation should be preferentially applied to achieve peak validity and reproducibility.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.