bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Androgen Availability on the Activation of Neuroprotective Pathways Following Traumatic Brain Injury
Authors: De La Cruz Lianne , Duncan Kelli 
Published: June 2021

Following traumatic brain injury (TBI), steroid hormones are neuroprotective. Specifically, estrogens decrease apoptotic signaling, neuroinflammation, oxidative stress, and have been shown to normalize glutamate concentrations. Furthermore, androgens also regulate neuroinflammation and mediate gliosis. However, the mechanisms underlying these influences are poorly understood. Cyclooxygenase (COX‐2) and prostaglandin E2 (PGE2) activation appear to be necessary for the injury induced upregulation of estrogen synthesis. This sex specific increase in estrogens promotes neuroprotection by increasing estrogen receptor‐α dependent decreases in neuroinflammation presumably by altering the activity of protein kinase A (PKA) or phosphoinositide‐3‐kinase (PI3K). While there is a considerable amount known about the role of estrogens in this pathway, very little is known about how androgens interact with estrogens to promote neuroprotection. The goal of this study was to further investigate the effect of androgens specifically, but also to identify if there are any interactions between androgens and estrogens on the activation of the COX‐2/PGE2 pathway. Prior to the concussive injury protocol, adult male and female zebra finches (Taeniopygia guttata) were implanted with androgens or an androgen antagonist (flutamide) and collected 1 week later. Activation of the COX‐2/PGE2 pathway was measured using analysis of quantitative polymerase chain reaction and immunohistochemistry. Preliminary data suggest that androgens are involved in estrogen mediated neuroprotection following injury and suggest a novel role for androgens following TBI.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effects of DNA sequence, endosomal pH, and lipid rafts/caveolae on uptake of human cathelicidin LL‐37/dsDNA complexes by monocytic cells
Authors: Rhodenizer Emma , Cho Katriel , Li Kelly , Craig Maria 
Published: June 2021

LL‐37, the only human homolog of the class of cathelicidin cationic peptides, has many beneficial roles in the immune system as an antimicrobial and pathogen‐sensing molecule. However, altered levels of LL‐37 have been linked to a growing number of diseases, including autoimmune diseases, cancer, cystic fibrosis, and asthma. LL‐37 forms complexes with bacterial and self‐DNA that are internalized by many immune cell types, and formation of these complexes both protects DNA from degradation by nucleases and increases internalization of LL‐37. LL‐37 and self‐DNA uptake appears be related to autoimmune disease because it is a pathway by which the immune system may recognize and respond to self‐DNA. LL‐37 can bind to DNA and RNA and bring them into endosomes, activating innate immune receptors known as toll‐like receptors 3 and 9 (TLR3 and TLR9). In order to examine this mechanism, we have used fluorescence microscopy to observe the uptake of 5‐FAM‐LC‐LL‐37 (10 μM) into THP‐1 monocytic cells in the absence and presence of 24‐mer dsDNA oligonucleotides (0.6 μM). We investigate sequence effects and observe that complexes formed with CpG and poly A enhance LL‐37 uptake, but that GpC and poly G are less effective. We have also examined the effect of endosome acidification on uptake and intracellular association of LL‐37 and dsDNA by performing uptake in the presence or absence of inhibitors of endosome acidification. To investigate the possible role of cholesterol‐rich lipid rafts and caveolae in uptake, we pre‐treated the cells with the cholesterol‐depleting agents methyl‐β‐cyclodextrin (MCD) and nystatin known to disrupt raft/caveolar structures. The mechanism for LL‐37/DNA uptake is an interesting area of study that may reveal ways to facilitate LL‐37‐mediated immune responses and help to create more specialized medicines.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
LPS decreases the expression of Monocarboxylate transporter‐1 (MCT1) in mouse monocytes
Authors: Ochrietor Judith D , Al‐Khatab Ryan 
Published: June 2021

The molecule Toll‐like Receptor‐4 (TLR4) recognizes Gram negative bacteria, specifically the lipopolysaccharide component (LPS) and initiates a signal transduction cascade leading to an inflammatory response. Recent studies by this laboratory suggest the cell adhesion glycoprotein Basigin (CD147) interacts with TLR4 via their transmembrane domains. The role of Basigin in mouse retina has been well‐studied and includes an association with Monocarboxylate Transporter 1 (MCT1) for metabolic support of photoreceptor neurons. The role of Basigin in innate immune responses is less‐well studied. Therefore, the response of Basigin to LPS was assessed and compared to that of TLR4. The response of MCT1 to LPS was also assessed. It was hypothesized that Basigin and MCT1 expression would increase in response to LPS. To test this, RAW 264.7 mouse monocytes were incubated in the presence of 1 mg/mL LPS in serum‐free medium for various times ranging from 2–24 hours. Control cells received PBS. The cells were collected, and RNA was isolated for gene expression analyses via quantitative‐reverse transcription PCR (q‐RT‐PCR). The expression of TLR4 decreased at 2 hours and increased at 24 hours of LPS induction, when compared to control samples, although no changes were determined to be statistically significant. The expression of Basigin was similar between control and LPS‐treated cells at all time points, except for 24 hours of induction, when Basigin expression was significantly lower in LPS‐treated cells. MCT1 expression was also similar between control and LPS‐treated cells at all time points, except for 24 hours of induction, when MCT1 expression was significantly lower in LPS‐treated cells. These findings do not support the hypothesis. The data for TLR4 expression in response to LPS in mouse monocytes are consistent with published reports. Although it was hypothesized that metabolic responses would increase in monocytes to support immune mechanisms, the data for MCT1 suggests that metabolism is reduced in activated monocytes, perhaps as a shift of resources from general cellular maintenance to induction of an innate immune response. The observed decrease in Basigin expression also did not support the hypothesis and suggests that the molecule is either regulated directly by the innate immune response or indirectly via its role in metabolism through MCT1. Future studies will assess the expression of Basigin and MCT1 at the protein level to better analyze the role of metabolism in the innate immune response.Support or Funding InformationUNF Office of Academic AffairsThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Homogenized mouse neural retina extracts stimulate an immune response in the mouse monocyte RAW 264.7 cell line
Authors: Ray Ashton Nicole , Ochrietor Judith D 
Published: June 2021

There are two main protein products of the Basigin gene. One protein, known as Basiginvariant‐1 is expressed in the neural retina, specifically by the photoreceptor neurons. The other protein, known as Basigin‐variant‐2 is expressed throughout the body, including monocytes, as well as Müller glial cells and the retinal pigmented epithelium of the eye. Studies by this laboratory using recombinant proteins indicate that the two Basigin gene products interact via their extracellular domains and that the region of the Ig0 domain of Basigin‐variant‐1 used to interact with Basigin‐variant‐2 stimulates a proinflammatory response in monocytes. The purpose of the present study was to determine the biological relevance of this proinflammatory response using mouse neural retina samples rather than recombinantly‐generated proteins. It was hypothesized that mouse neural retina extracts would induce an immune response in mouse monocytes. Mouse neural retinas were obtained using an approved protocol and homogenized in phosphate buffered saline (PBS). The mouse neural retina extracts were then incubated with mouse monocytic RAW 264.7 cells. After 24 hours, the cell culture medium was collected and assayed for the expression of the pro‐inflammatory cytokine interleukin‐6 (IL‐6) via an ELISA and the cells were collected for RNA isolation and subsequent quantitative reverse transcription PCR (q‐RT‐PCR). Cells treated with a similar volume of PBS served as the controls. It was determined that incubation of the neural retina extracts with the RAW 264.7 cells elicits a proinflammatory response in the monocytes and that the expression of the innate immune molecule TLR4 significantly increases in expression in those cells, when compared to the response observed with PBS treatment. The data suggest a biological relevance for the observation that recombinant Basigin‐variant‐1 interacts with Basigin‐variant‐2 to stimulate a proinflammatory response in monocytes. This study is important for a better understanding of immune response aspects of diabetic retinopathy and other diseases in which the retinal pigmented epithelium is compromised and can allow the infiltration of monocytes into the neural retina.Support or Funding InformationUNF Office of Academic AffairsThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Synthesis and Evaluation of a Photoswitchable COX‐2 Inhibitor
Authors: Denison Madeline , Streu Craig Nolan 
Published: June 2021

The research being presented herein is focused on making a drug that competitively and selectively inhibits cyclooxygenase‐2 (COX‐2) in response to a given wavelength of light, thereby reducing side effects. Cyclooxygenase‐2 is an enzyme primarily responsible for synthesizing prostaglandin, which generates inflammation in response to an infection or injury. Overproduction of prostaglandin can lead to painful inflammation like rheumatoid arthritis and osteoarthritis. Therefore, a COX‐2 inhibitor can solve this issue of inflammation by inhibiting the synthesis of prostaglandin.Before the advent of selective COX‐2 inhibitors, drugs targeting prostaglandin production were not as selective and also inhibited Cyclooxygenase‐1 (COX‐1), which could lead to unwanted side effects, like ulcers and gastrointestinal toxicity. To address this problem, “coxib” drugs were created to selectively inhibit COX‐2. While these drugs worked well in reducing inflammation, long‐term use was found to increase the risk of adverse vascular side effects. These side effects are thought to arise, in part, as a result of the role of COX‐2 in the maintenance of the vascular system. The research being presented aims to eliminate this side effect by making a drug that can target COX‐2 at the site of inflammation, without affecting the vascular system.The drug being synthesized is an azologue of a validated COX‐2 selective inhibitor. Azologues are modified to contain a nitrogen‐nitrogen double bond between two aromatic rings. Molecules containing this moiety can change conformation trans to cis or cis to trans in response to near UV or visible light, respectively. It is this change in conformation that creates a difference in target binding in the presence or absence of the appropriate wavelength of light. The target compound was designed to exist in the trans conformation in the absence of light. In silico binding analysis suggests that this is the active conformation of the inhibitor. The synthesis of the target molecule will be disclosed and its photophysical characterization by UV/Vis spectrophotometry will be outlined.Support or Funding InformationAlbion College Foundation for Undergraduate Research, Scholarship and Creativity ActivityThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Quantitative Survey of NAD+ Flux in Aged Mice
Authors: McReynolds Melanie R. , Chellappa Karthikeyani , Chu Qingwei , Baur Joseph A. , Rabinowitz Joshua 
Published: June 2021

Decline of NAD+ is associated with aging and disease; hence this critical metabolite is proposed as a master regulator of age‐dependent pathology. NAD+ is found in all living cells and is an essential coenzyme that broadly impacts metabolism and protein covalent modification. NAD+ depletion contributes to mitochondrial dysfunction, which is a classic hallmark of aging. Redox state and the rates of synthesis and degradation of the NAD+ chemical backbone govern the cellular concentration of NAD+. NAD+ decline during aging reflects depletion of the total NAD(H) pool, rather a shift in the NADH/NAD+ ratio, suggesting defective NAD+ synthesis and over‐consumption of NAD+ by cleaving enzymes. Concentration measurements are ill‐suited to distinguish these possibilities. Thus, there is a critical need to examine NAD+ metabolic flux, i.e. the rates of production and consumption of the NAD+ chemical backbone. To this end, we used isotope‐labeled NAD+ precursors, mass spectrometry, and quantitative modeling to determine NAD+ fluxes in young and aged mice. Tissue‐specific measurements of NAD+ labeling enabled organ‐specific assessment of NAD+ fluxes. These experiments identified accelerated NAD+ production and consumption in aging, and thus rational targets for intervention. Understanding of NAD+ fluxes will lay the foundation for understanding how NAD+ homeostasis is achieved: What are the primary control mechanisms that determine proper NAD+ concentration and fluxes? How do these go wrong in aging and disease?Support or Funding InformationHHMI Hanna H. Gray Fellows Program Burroughs Wellcome Fund Postdoctoral Enrichment ProgramThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Novel CBWD Gene Products Augment Mammalian Zinc Homeostasis
Authors: Ogo Ogo Agbor , Obochi Godwin Oche , Valentine Ruth , Ford Dianne 
Published: June 2021

The CBWD genes (coding for COBW domain‐containing proteins) was previously identified through an in silico search of the human genome for the presence of a zinc‐responsive element known as Zinc Transcriptional Regulatory Element (ZTRE)1. The human CBWD gene family consist of six isoforms with different chromosomal and cytogenetic locations and exhibit a remarkable nucleotide and amino acid sequence conservation. The prokaryotic homologues of CBWD proteins belonging to the GOG0523 family of proteins have been reported to have roles in zinc homeostasis2, however, no known role has yet been documented for the mammalian types. The discovery that the zinc‐sensitive element (ZTRE) occurred in multiple copies of the CBWD genes was intriguing and triggered further investigations into a likely role for this gene family in mammalian cellular zinc handling and/or trafficking. Moreover, we reported a protein that acts at the ZTRE site to mediate regulation of zinc homeostatic genes and found CBWD genes to be a prominent feature3. Using Caco‐2 cells as in vitro model of human enterocytes, we demonstrate the ability of CBWD genes to respond to changes in zinc content at both transcriptional and post‐transcriptional levels evidenced by decreased transcript and overexpressed protein abundance in response to increased extracellular zinc concentration. We also show that increased expression of CBWD protein through a transgene extended cellular tolerance to extreme windows of zinc availability, demonstrating the potential of the human CBWD gene products to augment cellular zinc buffering. This potential buffering ability of CBWD gene products may be effected through cellular zinc redistribution evidenced by a less punctate zinc distribution in cells made to overexpress CBWD protein compared to control cells. Furthermore, overexpression of COBW protein attenuated the responsiveness of a zinc‐sensitive metallothionein promoter, indicating an action consistent with a role in zinc trafficking or buffering. These findings give plausible evidence in support of the involvement of the mammalian CBWD gene products in cellular zinc homeostasis.Support or Funding InformationThis work was supported by the Nigerian Tertiary Education Trust Fund through Benue State University, Makurdi, Benue State NigeriaThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Anti‐apoptotic effect of Korean ginseng extract on aging‐induced ovary via inhibition of p63 signaling pathway in mouse
Authors: Song Ji‐Hyeon , Chei Sungwoo , Seo Young‐Jin , Lee Kippeum , Jin Heegu , Oh Hyun‐Ji , Oh Jae‐Hoon , Jang Hoon , Choi Youngsok , Lee Boo‐Yong 
Published: June 2021

BackgroundThe problem of women's subfertility has been steadily increasing worldwide, and many studies are under way to treat it. The ovary is a key element in the problem of subfertility, and it is very important to maintain integrity. Recently, the pregnancy age of women is increasing, and so the function of the ovary is deteriorated with aging. Korean ginseng has been widely used as a herb medicine and it is known to contain many beneficial biological properties. We investigated the effect of Korean ginseng extract (KGE) on ovary function of female.MethodsThe ovaries were harvested from 6‐month‐old female mice and cultured in the KGE‐treated media for 24 hours. After that, RNA was extracted from the control and KGE‐treated groups and microarray was performed. In addition, based on the microarray data, the gene expression was verified by qPCR.ResultsAging dramatically increased expression of apoptosis regulatory factors in ovary, but expression of these factors was significantly reduced in the KGE‐treated groups. Expression levels of apoptosis regulatory factors such as p63, NOXA, BCL2 and BAX were increased in the ovary with aging. KGEs reduced the expression level of these factors. Consequently, KGEs helps to maintain ovary function by suppressing apoptotic damage caused by aging.ConclusionsWe suggest that KGEs protect against aging‐induced ovary damage by inhibiting apoptosis signaling pathway.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Cardiometabolic Profile after Pediatric Cancer Treatment: Insight into HDL Composition and Nutritional Intake
Authors: Belanger Veronique , Diallo‐Blais Simon Saliou , Robert Carol‐Ann , St‐Martin Juliette Sauve , Beaulieu‐Gagnon Sabrina , Drouin Simon , Bertout Laurence , Bouchard Isabelle , Laverdiere Caroline , Sinnett Daniel , Marcil Valérie 
Published: June 2021

Few studies have investigated the impact of pediatric cancer treatment on cardiometabolic health, although chemotherapy in children can cause rapid weight gain, transient hypertension, elevated blood glucose and hyperlipidemia. Besides, we have previously shown that young survivors of childhood leukemia are at increased risk of having the metabolic syndrome, dyslipidemia, hypertension and altered high‐density lipoprotein (HDL) composition. This study aims to examine the cardiometabolic profile of children after cancer treatment in relation to their diet, as well as HDL2 and HDL3 composition.MethodsPatients were recruited at Sainte‐Justine University Health Center in Montreal as part of the VIE Program (Valorization, Implication, Education). Fasting blood samples were collected and we assessed participants' anthropometric, metabolic, and biochemical profiles. Three day food records were used to evaluate dietary intake. HDL2 and HDL3 fractions were isolated from plasma by ultracentrifugation, and total protein and lipids were measured by colorimetric reactions.ResultsTo date, 63 patients (44.4% boys) were recruited. Mean age was 11.7 ± 5.6 years and 46.0% were treated for acute lymphoblastic leukemia. The time elapsed since the last treatment was 17.0 ± 9.7 months. We found that 25.4% of participants (n=16/63) had hypertension, 22.2% (n=14/63) were obese and 8.9% (n=5/56) were insulin resistant. One third of patients had dyslipidemia (n=21/63), a risk that was increased by age (OR: 1.31, 95%CI: 1.16–1.50, P<0.01). Patients over 10 years old had insufficient intakes of several nutrients (vitamins A and E, folate, magnesium, zinc). Compared to healthy children, the proportion of esterified cholesterol in HDL2 was lower (18.6 ± 1.2% vs. 11.9 ± 1.4%, P<0.01), but protein content was higher (41.1 ± 1.6% vs. 48.8 ± 1.0, P<0.01). The proportion of esterified cholesterol was also lower in HDL3 fractions of patients treated for cancer (12.6 ± 1.3% vs. 10.1 ± 0.7%, P<0.01).ConclusionThese results indicate cardiometabolic disturbances and anomalies in HDL composition in children shortly after cancer treatment. They emphasize the need for nutritional interventions in this high‐risk population.Support or Funding InformationThis work is funded by The Foundation Centre de cancérologie Charles‐Bruneau and The Joy of Eating Better Foundation and the CHU Sainte‐Justine Foundation.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Lipid rafts transduce force to TREK‐1 channels via phospholipase D
Authors: Petersen E. Nicholas , Gudheti Manasa , Pavel Mahmud Arif , Murphy Keith R , Ja William , Jorgensen Erik , Hansen Scott 
Published: June 2021

The transduction of force into a biological signal is critical to all living organisms. Recently, disruption of ordered lipids has emerged as an ‘atypical’ force sensor in biological membranes; however, disruption has yet to link with canonical channel mechanosensation. We show here that force‐induced disruption and lipid mixing activates TREK‐1. This activation is dependent on PLD2 which transduces the force into the chemical signal phosphatidic acid that is then sensed by TREK‐1 with a latency of <3 ms. TREK‐1 then produces a mechanically induced change in membrane potential. These experiments establish the ordered lipid as the force sensor, PLD2 as the primary chemical transducer, and the ‘mechanosensitive’ ion channel TREK‐1 as a downstream effector of mechanical transduction. Confirming a central role for PA singling in force transduction, genetic deletion of PLD2 decreases mechanosensitivity and pain thresholds in D. melanogaster.Support or Funding InformationNATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKENATIONAL INSTITUTE OF AGEINGHOWARD HUGHES MEDICAL INSTITUTEThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.