bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of Cyclin A2 In Aging Hippocampus And rRna Dynamics
Authors: Alves Michele Joana , Goksel Mustafa , Fair Summer , Nunez Samara Mendez , Kaya Behiye , Mustafa Hasnaa , Czeiler Catherine , Otero Jose 
Published: June 2021

BackgroundNovel functions of cyclin A2 (CCNA2) have been demonstrated including DNA synthesis initiation and progression, DNA repair, and protein translation through RNA binding. Previously, we reported that loss of CCNA2 leads to hippocampal defects characterized by abnormal DNA repair and impaired performance on behavioral tests due to memory and learning deficits. Abnormalities in RNA processing and synaptic plasticity are mechanisms associated with deficits in memory and aging. This study was addressed to investigate effects of cyclin A2 loss on modulation of RNA processing in the hippocampus of aged mice.MethodsAll work involving animals was performed under the auspices of a protocol approved by the Ohio State University Institutional Animal Care and Use Committee. CamkIIα‐cre mice were interbred with CCNA2fl/fl mice to achieve adult ablation of CCNA2 in the hippocampus and cerebral cortex. To evaluate brain morphology, animals were sacrificed at 8 months. After fixed in 4% paraformaldehyde, crysections were obtained at 12 μm. Electron microscopy was performed and number of synapses and polyribosomes were quantified.ResultsUltrastructural analysis of Stratum Moleculare (SM) and Reticulare (SR) in 8mo mices showed a decrease of the synapse density in CamkIIαcre CCNA2 fl/fl mices as compared with control. However, quantity of ribosomes was increased only in SM of the hippocampus in mutant mices. Immunostaining for ribosomal RNA (rRNA) revealed an accumulation of rRNA granules in dentate gyrus and Cornu Ammonis (CA) both regions of the hippocampus. Quantitative analysis resulted an increased rRNA in the SR. To elucidate if mechanisms of translational regulation are modified by the lack of CCNA2 we screened for alterations of 40S ribosomal protein S6 (S6), and translational repressor eukaryotic initiation factor 4E binding protein (ELF4E) and cytoplasmic polyadenylation element binding protein 1 (CPEB1).ConclusionsOur data shows a distinct role for CCNA2 in adult hippocampus in the regulation of synaptic density as well as the prevention of rRNA granule formation. Alterations in RNA dynamics caused by loss of CCNA2 may be implicated in neuronal disorders and neurodegeneration.Support or Funding InformationThis work was sponsored by NIH/NHLBI grants RO1 HL132354This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Prion Deposition in the Retina of Sporadic Cruetzfeldt‐Jakob Disease
Authors: Goodwill Vanessa , Lin Jonathan , Sigurdson Christina , Geschwind Michael , Sanchez Henry 
Published: June 2021

IntroductionHuman spongiform encephalopathies, also known as prion diseases, are a rare group of infectious, heritable, and acquired diseases leading to rapid cognitive decline. Prion diseases are considered a serious public health threat due to the high level of infectivity and delayed presentation. Up to 50% of patients with prion disease develop visual symptoms during their clinical course, possibly secondary to abnormal prion protein (PrPSc) accumulation within the eye or within the visual pathway in the brain. Few studies, however, have investigated the presence and deposition pattern of PrPSc within the eye of patients with sporadic Creutzfeldt‐Jakob disease (sCJD). Knowing the presence or levels of PrPSc in the eye is important to assess the potential risk of transmission from common ophthalmic surgical procedures (cornea transplantations and cataract extractions). Additionally, the current gold standard of diagnosis for prion disease remains brain autopsy. If PrPSc expression is present consistently in the eye, ocular imaging modalities with PrPSc‐binding compounds may potentially enable earlier diagnosis. Here, we investigate the expression of PrPSc within retinas of confirmed prion disease cases collected from post‐mortem enucleations.MethodsFrom December 2015 to May 2017, 28 eyes were collected from 14 autopsies of clinically suspected prion disease and 6 of non‐prion disease at a single institution. sCJD was confirmed in all cases by brain autopsy and genetic analysis of the PRNP gene. Immunohistochemistry was performed with antibodies against PrP and PrP deposition within the retina was evaluated and compared with normal controls. Subjects included both male and female patients with ages ranging from 51–80 years old. The clinical disease course ranged from 2–24 months.ResultsIn twelve of the fourteen prion disease cases, PrPSc deposits were observed in the retina by immunohistochemistry. PrPScwas limited to the outer and inner plexiform layers of the retina and was most prominent in the outer plexiform layer, with the majority of cases exhibiting a coarse, 5–10 um well‐aligned ovoid deposits. Controls showed no PrPSc staining in any retinal layers. In the sclera, cornea, lens, and optic nerve, no deposits were observed.ConclusionPrPSc deposits were present in a majority of retinas of patients with confirmed prion disease, primarily within the outer plexiform layer, and these deposits can be detected immunohistochemically. Our findings confirm previous isolated reports of retinal PrPSc deposition in the largest series of documented prion cases to date. We suggest that the retina potentially serves as a diagnostic target in clinically suspected prion disease. Additionally, retinal involvement may contribute to visual symptoms commonly associated with prion 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.
Astrogliosis and downregulation of EAAT2 in rats infused with Nef transfected astrocytes.
Authors: Valles Ortiz Jaydie M. , Cruz Myrella L. , Rodriguez Yarelis L. , Cintron Kevin M. , Noel Richard J. 
Published: June 2021

Astrocytes play a major role in homeostasis and neuronal function by preventing excitotoxicity in the CNS. During HIV infection, astrocytes are reported to produce early viral proteins such as Nef, which is known to cause neurotoxicity. Excitatory amino acid transporter 2 (EAAT2) is one of the major astroglial transporters involved in the regulation of extracellular glutamate concentration. We investigated astrocytes transfected with Nef to understand the effect on learning, astrocyte morphology and glutamate transporter expression. Primary rat astrocytes expressing Nef or GFP were infused in the right hippocampus of 30‐day‐old male Sprague Dawley rats. Learning was assessed by Morris water maze five days after infusion. Brain tissues were collected for immunofluorescence staining and the morphological assessment of astrocytes and EAAT2 expression was assessed in different areas of the hippocampus (CA3 and dentate gyrus) using Image J software. In astrocytes, glial fibrillary acidic protein (GFAP) area fraction was significantly increased (P<0.05), while EAAT2 expression was significantly decreased (p<0.05) in the Nef‐treated group when compared to GFP controls. No differences in the length of processes in astrocytes were found, however the number of secondary processes was increased in the Nef‐treated animals. The increase of astrogliosis as measured by GFAP staining, the number of secondary processes, and the decrease of EAAT2 correlates with the learning impairment shown by the Nef‐treated group. These results suggest that there might be an astrocyte dysfunction that affects glutamate uptake at the synaptic cleft leading to neuronal toxicity.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effects of Alcohol on Innate Immune Responses of BV‐2 Microglial Cell Line without Type 7 Adenylyl Cyclase
Authors: Hu Yawen , Yoshimura Masami 
Published: June 2021

Alcohol consumption affects immune cell functions and induces neuroinflammation. The mechanism of ethanol's action on the immune system however, are not fully understood. Cyclic AMP (cAMP) is known for its immunosuppressive effects and also is required for proper development of the immune system. Previous work in our laboratory has demonstrated that ethanol enhances the activity of adenylyl cyclase (AC) in an isoform‐specific manner. Type 7 AC (AC7) is most enhanced by ethanol, and is highly expressed in immune cells including macrophages. Therefore, we hypothesize that AC7 plays an important role in alcohol's effects on innate immune functions of microglia and on neuroinflammation through a cAMP pathway. To test this hypothesis, we generated AC7 knockout (KO) cell lines from the mouse BV‐2 microglia cell line by CRISPR‐Cas9 mediated genome editing. A cAMP accumulation assay was used to confirm AC7 KO. The effects of ethanol on innate immune responses of BV‐2 cells with or without AC7 were examined by measuring phagocytosis and oxidative bursts via flow cytometry.The cAMP accumulation assay on wild type (WT) BV‐2 cells showed enhancement of cAMP production in the presence of prostaglandin‐E1 (PGE1). cAMP production was further enhanced by addition of ethanol, as well as an AC7 specific activator, sphingosine‐1‐phosphate (S1P). cAMP production in AC7 KO cells was drastically decreased and did not respond to either ethanol or S1P. The results suggest that AC7 is the dominant form of AC in the microglia. Phagocytic activity measured using fluorescently labeled bacteria was significantly suppressed in the presence of isopropanol (Iso) in WT BV‐2 cells, while Iso did not significantly change the phagocytic activity of AC7 KO cells. Ethanol further reduced phagocytic activity of WT cells in the presence of Iso. Ethanol alone did not suppress phagocytosis in WT BV‐2 cells, but significantly inhibited phagocytosis in AC7 KO cells. This latter difference in response was unexpected and may indicate that AC7 can protect microglia from ethanol‐induced inhibition of phagocytosis. The production of reactive oxygen species was measured using dihydrorhodamine 123. We did not observe any notable differences in oxidative burst between WT and AC7 KO BV‐2 cells. The results indicated that AC7 elimination altered ethanol effects on some of the immune functions of BV‐2 cells, which is consistent with our hypothesis. We plan to further examine innate immune functions including bacterial killing, nitric oxide production, and proinflammatory cytokine expression in AC7 KO cells.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Glutamic‐Oxaloacetic Transaminase Combined with Metabolic Therapy in a Mouse Model of Amyotrophic Lateral Sclerosis
Authors: Rogers Christopher Q. , Ramirez Melissa , Landon Carol S. , DeBlasi Janine M. , Koutnik Andrew P. , D'Agostino Dominic P. 
Published: June 2021

Amyotrophic lateral sclerosis (ALS) also known as Lou Gehrig's Disease is a progressive disease of neuronal degeneration in the spinal cord, brainstem and motor cortex resulting in impaired motor function and eventual demise. There is currently no widely accepted, effective treatment for this condition.Glutamate (Glu) excitotoxicity is a process in which excessive Glu‐induced stimulation of neurons can lead to their damage and death. The drug riluzole (Rilutek) is the only medication approved by the FDA for ALS. The drug appears to slow the disease's progression in some people, perhaps by reducing CNS Glu that is often present in elevated levels in ALS patients.Oxaloacetate (OX) is an anaplerotic molecule and initiation point for the activation of Kreb's Cycle. Previous work has demonstrated the ability of exogenous OX to reduce CNS Glu levels. Glutamic‐oxaloacetic transaminase (GOT) is an endogenous enzyme that catalyzes the following reaction: Glutamate + Oxaloacetate ↔ Alpha‐Ketoglutarate + Aspartate. GOT with OX has been shown to increase the removal of Glu from the blood and the CNS, thereby reducing excitotoxicity and improving neuronal health.A novel metabolic therapy known as the Deanna Protocol (DP) has been used effectively in ALS patients and mice. It consists of dietary supplements (arginine, alpha‐ketoglutarate, medium‐chain triglyceride oil, phenibut and coenzyme Q‐10) to support mitochondria and the Kreb's Cycle.Here we investigate the DP alone or in conjunction with GOT and OX as a potential therapy. Twenty ALS mice were randomly separated into four groups. Mice were singly‐housed. The control group received standard chow mash. The DP group received DP mixed with standard chow mash. The GOT/OX group received injections of GOT 3X/wk and OX mixed with standard chow mash. The DP + GOT/OX received injections of GOT 3X/wk and OX mixed in a DP‐containing chow mash.Compared to the control group, the three treatment groups each had significantly longer survival times, improved motor performance, and better neurological scores. The treatments were neither additive nor synergistic, suggesting unique therapeutic effects derived from each treatment. These findings suggest that the DP and/or GOT/OX treatment may have therapeutic application in patients with ALS and perhaps other neurologic disorders.Support or Funding InformationThis study was supported by Winning the Fight against Neurodegenerative Diseases grant #111990. Oxaloacetate kindly provided by Alan Cash.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 Lipocalin‐2 (LCN2) and High Mobility Box Group 1 (HMGB1) in Acetaminophen‐induced Acute Liver Failure
Authors: Reed E'Joven D. , Shashidharamurthy Rangaiah , Bhave Vishakha S. 
Published: June 2021

Acetaminophen (APAP) overdose is the most common cause of Acute Liver Failure (ALF). Following APAP overdose, toxicity is initiated by the conversion of APAP to its reactive metabolic N‐acetyl‐p‐benzoquinone imine (NAPQI) by CYP2E1/CYP3A4. NAPQI binds covalently to mitochondrial proteins forming 3‐(cysteine‐S‐yl)‐acetaminophen (APAP‐Cys). This generates initial hepatotoxicity in the form of centrilobular necrosis and sterile inflammation. Lipocalin‐2 (LCN2), is an acute‐phase innate immune protein, upregulated during tissue injury in various organs including the liver. Recently we have demonstrated that LCN2 is pro‐inflammatory and elevated during APAP overdose in mouse model. Interestingly, LCN2 knockout (LCN2 KO) mice exhibit protection from APAP overdose compared to its wild type (WT) littermates. During APAP overdose there is necrosis of hepatocytes, these hepatocytes release Damage Associated Molecular Patterns (DAMPS) that further exacerbate the inflammatory process. One such DAMP is High Mobility Group Box 1 (HMGB1). However, the role of LCN2 and HMGB1 in APAP overdose has not yet been investigated.Present study investigates the molecular mechanism of LCN2 during the progression of acute liver injury in APAP overdose model. We hypothesize that during APAP induced ALF, LCN2 induces the expression and translocation of HMGB1 which in turn mediates inflammation and progression of injury. An in vitro model of HepG2 cells as well as an in vivo model of WT and LCN2 KO mice will be utilized to test our hypothesis. HepG2 cells will be treated with recombinant LCN2 to investigate whether exogenous LCN2 can cause induction and translocation of HMGB1. Translocation of HMGB1 will be assessed by immunofluorescence staining. Serum and tissues samples of WT and LCN2 KO mice subjected to APAP overdose will be assessed for expression of HMGB1. APAP‐cys formation will be measured in WT and LCN2 KO using the High‐Performance Liquid Chromatography method to ensure comparable bioactivation based injury between the WT and LCN2 KO mice. Lastly, histopathology will be performed on liver samples from both groups to assess liver pathology. It is anticipated that LCN2 mediates progression of liver injury in APAP overdose via HMGB1.Support or Funding InformationPhiladelphia College of Osteopathic Medicine‐Division of ResearchThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Histone Deacetylase 3 Promotes Liver Regeneration and Liver Cancer Cells Proliferation through Signal Transducer and Activator of Transcription 3 Signaling Pathway
Authors: Lu Xufeng , Zhuang Xiang , Zhu Yongjie , Cao Xiaoyue , Shao Mingyang , Xu Qing , Zhou Yongjie , Wu Zhenru , Ji Hongjie , Lu Qing Richard , Yang Jiayin , Shi Yujun , Liao Jiayu , Zeng Yong , Bu Hong 
Published: June 2021

Histone deacetylase 3 (HDAC3) plays pivotal roles in cell cycle regulation and is often aberrantly expressed in various cancers including hepatocellular carcinoma (HCC), but little is known about its role in liver regeneration and liver cancer cells proliferation. Using an inducible hepatocyte‐selective HDAC3 knockout mouse, we find that lack of HDAC3 dramatically impaired liver regeneration and blocked hepatocyte proliferation in the G1 phase entry. HDAC3 inactivation robustly disrupted the signal transducer and activator of transcription 3 (STAT3) cascade. HDAC3 silencing impaired the ac‐STAT3‐to‐p‐STAT3 transition in the cytoplasm, leading to the subsequent breakdown of STAT3 signaling. Furthermore, over‐expressed HDAC3 was further associated with increased tumor growth and a poor prognosis in HCC patients. Inhibition of HDAC3 expression reduced liver cancer cells growth and inhibited xenograft tumor growth. Our results suggest that HDAC3 is an important regulator of STAT3‐dependent cell proliferation in liver regeneration and cancer. These findings provide new insights into the HDAC3‐STAT3 pathway in liver pathophysiological processes.Support or Funding InformationThis work was supported by grants from the Natural Science Foundation of China (NO. 81472303), the National Key Clinical Project, and the Major Science and Technology Project of Science & Technology Department of Sichuan Province (2017SZ0003).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Heavy Baristas, Heavy Orders: Customers Order More Calories from Overweight Baristas
Authors: Wansink Brian , Junghans Astrid 
Published: June 2021

Purchasing coffee is a daily ritual for many consumers. How might various characteristics of the barista influence what a customer decides to order? If baristas do have a small calorie‐biasing influence on an order, when repeated hundreds of times, could calories become kilograms? 1,010 customers were observed as they ordered at 34 different Starbucks locations. Customer and barista characteristics, customer orders, and the calories in these orders were coded. Analyses tested the effect of barista weight and gender on the likelihood that consumers would purchase add‐ons to their order, as well as the calories in these items. Customers ordering from overweight baristas appeared to be twice as likely to order food with their drink and to order extra add‐ins to their drink. While the overall calories in the drinks were not different, the total calories ordered (food calories plus drink calories) was greater for those who ordered from overweight baristas compared to normal weight ones. The barista's body size appears to be related to the number of calories ordered by consumers. This underscores the wide range of primes and cues that exist in restaurants that can unknowingly bias what and how much one orders. Pre‐committing to an order before arriving at a restaurant will reduce the influence of environmental primes and cues.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
First Seen First Bought: Supermarket Aisles Order and Spending
Authors: Wansink Brian , Stein Kate , Lutz Richard 
Published: June 2021

In grocery stores, product location may be key to more persuasive marketing and increased sales; we investigated the links between aisle location, likelihood of aisle entry, and purchase incidence. We observed the behaviors of 328 shoppers at four different supermarkets, recording how often they entered each aisle and how many items they selected from that aisle. We found that aisle content and amount of time spent in the store determine the likelihood of aisle entrance. As a shopping trip continues, a number of factors may drive a shopper into greater selectivity in aisle entrance: impatience, product assortment in that aisle, and time pressures. Shoppers who enter an aisle later in their shopping trip will be more likely to select a product, yet they make fewer purchases in that aisle than in aisles they shopped earlier in their trip. Diminished motivation levels and decreased enthusiasm may prompt this observed effect.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
High fat diet risk factor for gingival Immunosuppression and cancer
Authors: Kaur Kawaljit , Eibl Guido Anahid , Jewett Anahid 
Published: June 2021

ObjectiveHigh fat diet leading to obesity has been associated with many diseases including cancer. We determined the effect of high fat diet and obesity in the phenotype and function of immune cell infiltrates within different tissues including gingival tissues of mice with wild type and targeted KRAS mutations in the pancreas.Experimental methodsConditional LSL‐KRASG12D and p48‐Cre or PDX‐1‐Cre mice were bred and their offsprings were used for the studies. Mice with both the KrasG12D and Cre allele were designated as mutant mice (KC). Mice with neither the KrasG12D nor the Cre allele were used as wildtype (WT). Mice were fed either a high fat, high calorie diet (HFCD) or a control diet (CD) for 4 to 6 months before they were used for experiments. NK cytotoxicity was determined by 51Cr release assay and cytokine secretion by ELISA.ResultsThe Following profiles were obtained for NK cell cytotoxicity and secretion of IFN‐g from NK cells purified from spleen of KC or WT mice fed either with CD or HFCD (WT(CD)>WT(HFCD)>KC(CD)>KC(HFCD). Immune cells from blood and pancreas exhibited similar pattern of cytotoxicity to those obtained from the spleen but inverse profile of IFN‐g and IL‐6 secretion (WT(CD)<WT(HFCD)<KC(CD)<KC(HFCD) was seen. Mice fed with HFCD when compared to CD had much less NK cells both in WT and KC mice in pancreas, adipose and gingiva.ConclusionMice fed with HFCD exhibited higher inflammatory index when compared to those fed with CD both in WT and KC mice. In addition, numbers and the cytotoxicity of NK cells were severely decreased in pancreas and gingiva of WT and KC mice fed with HFCD. High fat diet exacerbates the progression of neoplastic lesions in KC mice and could be responsible for the oral mucosa pathologies due to decrease function and numbers of key immune effectors.Support or Funding InformationP01 CA163200; PAPD and XO clubThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.