bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dietary Restriction modulates sleep in Drosophila Melanogaster
Authors: Varamini Behzad , Joel Hayley , Lee Jin , Newman Emma , Robinson Krystal , Smith Zachary 
Published: June 2021

Sleep deprivation has catastrophic metabolic and physiological consequences in numerous organisms, from fruit flies to humans. Dietary restriction (DR), a limitation of calories in the absence of malnutrition, has been shown to dramatically improve the health and longevity of a number of species, and evidence shows that this intervention may have the potential to overcome some of the molecular and neurological deficits seen in aging and sleep decline. Using a 17‐beam infrared‐light paradigm as well as gene expression analysis, this study demonstrates that restriction of amino acids has significant effects on sleep/wake patterns in Drosophila Melanogaster, as well as alters the expression of genes essential to maintaining homeostatic sleep.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Myeloperoxidase‐Derived 2‐Chlorofatty Acids Make Neutrophils Go NETs
Authors: Palladino Elisa N. D. , Katunga Lalage A. , Ford David A. 
Published: June 2021

Neutrophils represent the major effector cells of innate immunity. One mechanism for neutrophil‐mediated microbe killing is through the release of neutrophil extracellular traps (NETs). NET formation (NETosis) involves the fusion of granule and nuclear contents, which are then released in the extracellular space to capture and kill microbes. Chlorinated fatty acids (2‐ClFAs) are a product of neutrophil activation as a result of the myeloperoxidase (MPO) product, HOCl, targeting plasmalogen phospholipids. In this study, we examined the role of 2‐ClFA as an important lipid mediator of NETosis. Treating human peripheral blood neutrophils with physiological levels of 2‐ClFAs led to the formation of NETs, characterized by MPO association with DNA and neutrophil elastase (NE) redistribution to the perinuclear area. NETs induced by 2‐ClFA treatment were as efficient in killing bacteria as those produced by stimulating neutrophils with phorbol myristate acetate (PMA), a potent activator of NETosis. Like PMA, 2‐ClFA‐induced NETosis is calcium‐ and protein arginine deiminase 4 (PAD4)‐dependent. Interestingly, while PMA‐induced NETosis requires neutrophil activation, 2‐ClFAs initiate the NETosis process without neutrophil activation and degranulation. Furthermore, unlike PMA, 2‐ClFA elicits NETosis in bone‐marrow derived neutrophils from MPO deficient mice. Overall, 2‐ClFA may have an important role in directing neutrophil fate following activation, mediating the production on NETs and providing a new pharmacological target to either enhance bacterial killing or reduce host injury during inflammation.Support or Funding InformationThis study was supported by research funding from the National Institute of Health R01 GM‐115553 to D.A.F.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
2‐Chlorofatty Acid: A Functional Connection between Neutrophils and Endothelial Weibel‐Palade Body Mobilization
Authors: Hartman Celine L. , Duerr Mark A. , Albert Carolyn J. , Neumann William L. , McHowat Jane , Ford David A. 
Published: June 2021

Endothelial dysfunction has been characterized as a hallmark of multiple inflammatory diseases, including sepsis and atherosclerosis. Neutrophil interactions with the endothelium may have profound effects on vascular wall biology and pathophysiology. Myeloperoxidase (MPO)‐derived oxidant products released from neutrophils can mediate inflammation and endothelial dysfunction. 2‐Chlorofatty acid (2‐ClFA) is a product of MPO‐derived HOCl targeting plasmalogen phospholipids, found abundantly throughout the body. Chlorinated lipids, produced and released by neutrophils, have recently been associated with multiple inflammatory diseases, but their impact on nearby endothelial cells has not been examined. This study tested the biological properties of the 16‐carbon 2‐ClFA molecular species, termed 2‐chlorohexadecanoic acid (2‐ClHA), on endothelial cells. An alkyne analog of 2‐ClHA, 2‐chlorohexadec‐15‐ynoic acid (2‐ClHyA), was synthesized and utilized to determine the subcellular localization of 2‐ClFA in human coronary artery endothelial cells. Experiments using a novel Click chemistry approach revealed 2‐ClHyA localizes to Weibel‐Palade bodies, which are endothelial‐specific storage granules containing multiple key bioactive molecules. 2‐ClHA and 2‐ClHyA significantly increase the surface expression of P‐selectin, as well as the release of von Willebrand factor and angiopoietin‐2 from endothelial cells. Functionally, 2‐ClHA and 2‐ClHyA increase neutrophil adherence to and platelets aggregation on the endothelium, as well as increase permeability of the endothelial barrier which has been tied to the release of angiopoietin‐2. Ongoing studies utilize Click chemistry to pulldown proteins which bind to 2‐ClHyA through biotinylated azide. Initial studies indicate multiple, unique proteins interact with 2‐ClHyA when compared to the non‐chlorinated fatty acid, and identification of these proteins may provide further mechanistic insight into 2‐ClHyA‐induced Weibel‐Palade body mobilization. These findings suggest that 2‐chlorofatty acid, a novel lipid produced by neutrophils under inflammatory conditions, promotes endothelial cell dysfunction, which may have broad implications in inflammation, thrombosis, and blood vessel stability.Support or Funding InformationThis work was supported in part by National Institutes of Health Grant R01 GM‐115552 (DAF) and American Heart Association Grant‐in‐Aid 15GRNT25750022 (DAF).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
SAC1 degrades its lipid substrate PtdIns4P in the ER to maintain a steep electrochemical gradient on donor membranes
Authors: Hammond Gerry , Zewe James , Sangappa Sahana , Wills Rachel , Goulden Brady 
Published: June 2021

Phosphatidylinositol 4‐phosphate (PtdIns4P) is one of the most functionally diverse molecules utilized by eukaryotic cells. It is both a metabolic hub for other crucial signaling lipids such as PtdIns(4,5)P2 and PtdInsP3, and a key molecule for recruitment of membrane and lipid transport proteins in its own right. Most recently, it has been proposed to form a “phosphoinositide‐motive force”, whereby transport of PtdIns4P molecules down their concentration gradient from the plasma membrane (PM) or Golgi to the ER drives counter transport of other lipids up their own concentration gradients. A critical requirement for this model is that the main PtdIns4P degrading enzyme, the integral ER phosphatase SAC1, hydrolyzes PtdIns4P in the ER in a “cis” configuration. Alternatively, it has been suggested that other functions of PtdIns4P are regulated by SAC1 hydrolyzing PtdIns4P directly in the PM in a “trans” configuration at membrane contact sites (MCS). However, such activity would surely disrupt lipid counter transport. Therefore, we sought to determine whether SAC1 acts in “cis”, “trans”, or both in mammalian cells. Acute chemical ablation of SAC1 activity drives ectopic accumulation of PtdIns4P in the ER, revealing “cis” activity. Furthermore, endogenous or ectopically expressed SAC1 localizes to the ER and Golgi, but does not constitutively or dynamically enrich at ER‐PM MCS. Forced recruitment of SAC1 to experimentally induced MCS does not produce robust “trans” activity on PM PtdIns4P. However, “trans” activity can be induced by adding an approximately 6 nm long helical linker between the ER anchor and the catalytic domain. Together, our results reveal that SAC1 operates in a “cis” configuration. This ensures a “phosphoinositide‐motive force” for lipid transport is effective, and also implies regulation of PM phosphoinositide signaling is tightly linked to non‐vesicular traffic of PtdIns4P at ER‐PM MCS.Support or Funding InformationThis work was supported by National Institutes of Health grant 1R35GM119412‐01This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The Anthrax Toxin: A Molecular Trojan Horse
Authors: Patel Heeral , Edmondson Riley Grace , Baugh Jessica Renee , Shabbir Sanah Zehra , Kenana Sireen 
Published: June 2021

Anthrax is a three protein component exotoxin released by the virulent bacterium Bacillus anthracis that causes cell lethality in its host. In humans and many animals, Bacillus anthracis can enter the body through the lungs, skin, intestines, or bloodstream. Symptoms of Anthrax poisoning are commonly displayed between one day to two months after initial contact. Once the bacterium spores enter the host organism, the spores germinate and the bacterium synthesizes and releases the anthrax endotoxin protein molecules in response to elevated CO2 levels. Anthrax toxin is composed of three protein molecules: protective antigen, edema factor, and the lethal factor. The protective antigen is released by the bacterium as an 83 kDa protein single chain, and then binds to the host cell receptors. It is then cleaved by proteases on the host cell into a smaller 63 kDa assembly competent monomer which assembles on the cell surface as a heptamer. This heptameric ring binds to edema factor and lethal factor. The pre pore three component complex is then endocytosed into the host cell. As the endosome acidifies to pH 5.0, the prepore protective antigen changes shape, and inserts into the endosomal lipid membrane. The bound edema factor and the lethal factor are gradually unfolded and threaded through the protective antigen pore translocon injection system. The translocated edema and lethal factors then refold in the cytoplasm. This threading is facilitated by a pH gradient. During the threading of the lethal and edema factors, the acidic residues of these proteins are first protonated, resulting in a positive charged state. As these enzymatic proteins are threaded through the pore, the proton is lost after crossing a critical phenylalanine clamp loop region and the protein continues to thread in a unidirectional manner into the cytoplasm. Once the translocated enzymes refold in the cytoplasm, the lethal factor disrupts cell signaling and the edema factor disrupts cell homeostasis. To study this translocation mechanism, one can use the 20 kDa N terminal portion of the lethal factor (called LFN) that binds to the pore and removes the enzymatic portion of the protein. Research is progressing where this translocation system is used to deliver drugs that are attached onto the LFN and be transported into cells in a very specific manner. Thus the understanding of this transport mechanism may be important for engineered drug delivery systems. The Olathe North MSOE Center for BioMolecular Modeling SMART Team used 3‐D modeling and printing technology to examine structure‐function relationships of anthrax.Support or Funding InformationThe Olathe North SMART Team is joint venture between the Medical Professions Academy and the Milwaukee School of Engineering.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Membrane localization of HspA1A, a stress inducible 70‐kDa heat shock protein, is mediated by the lipid phosphatidylserine
Authors: Bilog Andrei Dominic , Nikolaidis Nikolas 
Published: June 2021

Seventy‐kilodalton heat shock proteins (Hsp70s) are molecular chaperones essential for regulating cellular homeostasis. Apart from their indispensable roles in protein homeostasis, specific Hsp70s, including HspA1A, also localize at the plasma membrane (PM) of 90% of human and mouse tumors and its PM presence has been associated with bad patient prognosis. However, it is currently unknown how HspA1A, a protein that lacks membrane localization signals, is translocated and anchored to the PM. We have recently demonstrated that HspA1A interacts with several lipids, including phosphatidylserine (PS), a lipid found primarily in the inner leaflet of the PM during normal cell growth. Taking into account that lipids recruit proteins to the PM, we hypothesized that the interaction of HspA1A with PS allows the chaperone to localize at the PM. To test this hypothesis, we determined the translocation pattern of HspA1A in three human cell lines and also whether the C2 domain of lactadherin (Lact‐C2), a known PS‐biosensor, inhibits this translocation. Specifically, cells were subjected to mild heat‐shock, a condition that does not induce apoptosis, and the PM‐localized HspA1A was quantified using confocal microscopy and cell surface biotinylation. These experiments revealed that in the absence of Lact‐C2, HspA1A's membrane localization increases during recovery from non‐apoptotic heat‐shock and this phenomenon is unrelated to PM‐charge. In the presence of Lact‐C2, however, HspA1A's membrane localization is inhibited. Furthermore, we used TopFluor‐PS, a fluorescent PS analog, and established that it co‐localizes with HspA1A. Collectively, these results strongly suggest that HspA1A's membrane localization, anchorage, and embedding depends on its interaction with intracellular PS. This discovery institutes PS as a new and dynamic partner in the cellular stress response and establish the foundation to directly assess the biological implications of this newly described function of Hsp70s.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Induction of Osteogenesis by Means of Continuous Delivery of Testosterone and TQ Using in Bone Fracture Rat Model
Authors: Benghuzzi Hamed A. , Tucci Michelle A. 
Published: June 2021

Potent anti‐oxidant extracts from natural products, as an alternative to conventional treatment of various diseases, have been utilized extensively in the recent years. For example, Nigella sativa, natural herbs have been used for many acute as well as chronic conditions. The specific objectives of this study were (1) to successfully deliver the active components of black seed, thymoquinone (TQ), and anabolic agent, testosterone (TE) at sustained levels using a tricalcium phosphate delivery system (TCPL); (2) to evaluate the effects TQ and TE on bone healing (induced femoral defect) in adult male rats. Sixty animals were randomly divided into five equal groups. Groups I and II animals served as controls, and shams, while groups III and IV served as TQ and TE experimental groups (40 mg of TQ or TE loaded TCPL). Group V animals served as TQ (40 mg)+TE (40 mg) treated group. Serum biomarkers, x‐rays, reproductive and vital organs were collected and analyzed. At the end of 30 days, animals were sacrificed and vital as well reproductive organs were collected and analyzed morphometrically. At the end of 60 days post treatment all animals were sacrificed and the results revealed the following: (i) gross anatomical observation indicated an increase in the healing pattern of animals in all experimental groups compared to the sham operated group, (ii) the progression of osteogenesis was in the following order: TQ+TE>TE>TQ>shams, and (iii) no significant differences where detected in the levels of total serum proteins, and maliondialdehyde; (iv) an increase in alkaline phosphatase (p<0.05) in all experimental animals compared to control and sham groups. Overall conclusion of this study demonstrated that TCPL sustained delivery of TQ plus TE can be used effectively to stimulate osteogenesis in rat 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.
GPR18 Distribution and Expression in Human Placenta
Authors: Yuil‐Valdes Ana , Mukherjee Maheswari , Anderson‐Berry Ann , Hanson Corrine K. , Berry Elizabeth , Nordgren Tara 
Published: June 2021

BackgroundOptimally functioning inflammation resolution systems during pregnancy are essential in regulating a series of complex processes that could degenerate into persistent inflammation and result in poor maternal‐child outcomes. Infants developing in a pro‐inflammatory intrauterine environment are at significantly higher risk for severe complications than infants born without pregnancy inflammatory risk factors.Specialized pro‐resolving lipid mediators (SPM) are chemical structures derived from polyunsaturated fatty acids. Resolution of acute inflammation is an active process regulated by SPM, including resolvin D2 (RvD2), a potent docosahexaenoic acid‐derived resolution‐phase mediator, which activates a cell surface G protein–coupled receptor, GPR18/RvD2.Preliminary data from our group indicate that the SPM RvD2 is significantly increased in maternal plasma taken at the time of delivery compared to cord blood plasma (3,450 vs. 689 pg/mL for maternal vs. cord, respectively, p<0.001), with further increases in the maternal plasma of cases with adverse maternal‐fetal outcomes, including NICU admission. Based on this data, we hypothesize that the placenta is a target site of action of SPM during perinatal growth and development. We identified the expression of the RvD2 receptor, GPR18 by immunostain on decidual cells, smooth muscle of the maternal and fetal arteries and syncytiotrophoblast, cytotrophoblast and macrophages of chorionic villi. Since the decidual cells showed significant expression of GRP18 therefore, the objective of this study was to analyze and categorize the different levels of staining intensity in this cell type.MethodsTen cross‐sections of placental tissues containing both maternal and fetal sides were stained for SPM‐binding receptor, GPR18 immunostaining, and digitized at 40× magnification using VENTANA iScan HT scanner. Our novel approach including Definiens Tissue Studio® software was used to quantify the cellular analyses of decidual cells in these digitized images that quantify low, medium, and high expressions for GPR18.ResultsThe majority of decidual cells showed medium or high GPR18 membranous and cytoplasmic expression (Figure 1). 20% of decidua cells had no areas of low expression. Seven out of ten samples had areas of medium expression that were greater than 50%. Areas of low expression ranged from 0–31%, while areas of medium expression ranged from 11–81%, and high expression ranged from 5–75%.ConclusionsThe decidual cells of the placenta have medium/high membranous and cytoplasmic expression of GPR18. SPM may be an important component of the inflammation physiology in the placental tissue. The expression of GPR18 may play a protective role in pregnancy and perinatal disease.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Profiling apolipoproteins in disease
Authors: Dreskin Elizabeth Jordan , Brampton Chris , Houser Brett , Hendricksen Amy 
Published: June 2021

Detecting changes in biomarker levels or even the presence of biomarkers in limited samples can be difficult with traditional ELISA techniques. Multiplexing magnetic bead based assays not only affords much higher sensitivity, but also allows for sample conservation by testing for multiple analytes in a single well. In this study, we used an apolipoprotein multiplex panel to screen for some of the traditional apolipoproteins within the statin pathway (ApoA1, ApoA2, ApoB, ApoC1, ApoC3, and ApoD , along with additional targets important for cardiovascular disease, neurobiology, cancer, and inflammation research; Apo E, Apo H, Clusterin (Apo J) and C‐Reactive Protein (CRP). Purchased serum samples representing several different diseases, including atherosclerosis, Diabetes Mellitus Type I, sepsis, Alzheimer's, and Traumatic Brain Injury, were diluted 1:50,000. With the exception of CRP levels in some sepsis samples, all readings were within range. We conclude that this technology, and specifically this Apolipoprotein 10‐plex, can be applied to many areas of disease research, and requires a minimum of sample of serum in order to generate robust data.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
RELATION ASYMMETRY FACIAL AND SYMMETRY FACIAL vs TIMES AND FIXATIONS TO BUILD A DIAGNOSIS IN A HISTOPATHOLOGY TASK
Authors: MONDRAGON EDWARD JAVIER ACERO 
Published: June 2021

The asymmetry facial is a signal morphometric that in the development embryonal increase by causes endogens how mutations, homozygosity, inbreeding, and causes exogens how minors epigenetic adaptations during environmental stresses maternal. During task of observation the perceptual load has individual differences relatively high by fixations over shape, size, brightness and color and the experience of observation, but don't exist references about its relations with asymmetry facial when is accepted in biology that asymmetry impose different performances functionalsMaterials and MethodsSecond‐year medical students 8 females (□ = 18.4 years) and 6 males (□ = 18.9 years) were calculated their facial asymmetry being n = 4 symmetrical and n = 9 asymmetric; In time of free interaction the entire population was challenged to the definitive histopathological diagnosis of basal cell carcinoma from digital images, measuring both duration and quantity of fixations.RESULTSBetween symmetric individuals and histopathological diagnosis, there was a negative correlation coefficient r = −0.9411 between the duration of their fixations (average 310 ms, DS = 40 ms) and the number of their fixations (mean 103, DS = 16 ), Which has significant differences in the performance of asymmetric individuals with a less negative correlation coefficient r = −0.743 between the duration of fixations (average 237 ms, DS = 28 ms) and the number of fixations (average 144, SD = fifty).ConclusionSymmetric individuals do less fixations and last longer in them when they make histopathological diagnosis of basal cell carcinoma with respect to asymmetric individuals who make more fixations and last less in each one.
Agnostic Pathology of Molecular Biomarkers in Smell Loss (Hyposmia)
Authors: Henkin Robert , Abdelmeguid Mona 
Published: June 2021

There are multiple pathologies which biochemically initiate and perpetuate smell loss (hyposmia). These pathologies are non‐neoplastic diseases and include viral‐type infections, allergic rhinitis, traumatic head injuries, inhalational anesthesia and several other pathologies. We have attempted to evaluate specific biochemical parameters, manifested as biomarkers, which identify the pathology underlying these various causes of hyposmia. While each of these pathologies reflects widely different initiating events to cause hyposmia the biomarkers underlying these events are similar in each pathology. These biomarkers are found in nasal mucus, the biological fluid which maintains olfactory receptors. These biomarkers are decreased nasal mucus concentrations of cAMP, cGMP and sonic hedgehog. The mechanisms for these changes are similar across each of these pathologies since these biomarkers reflect diminished activity of these moieties which act as growth or transcription factors which stimulate stem cells in the olfactory epithelium to initiate growth and perpetuation of olfactory epithelial receptor cells. Similarities in these growth factor abnormalities across these multiple initiating pathological events are the basis for this agnostic determination of the biomarkers which induce hyposmia. Indeed, correction of these biochemical abnormalities with treatment with the phosphodiesterase inhibitor theophylline increases nasal mucus levels of each of these biomarkers in each pathology which thereby improves hyposmia in each pathological entity and establishes the agnostic character of these biomarkers.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.