bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting Mouse Oocyte Methylome from Polar Body by Single‐cell Whole Genome Bisulfite Sequencing
Authors: Lee Tin‐Lap , Chan Wai‐Yee , Qian Yan , Qin Cao , Yip Kevin Yuk‐Lap , Chow King Lau , Tang Nelson LS. , Liao Jinyue , Luk Alfred Chun Shui , Suen Hoi Ching , Lee Wing Tung , Zhao Ming Peng , Kong Grace Wing Shan , Chung Hoi Sze , Leung David Chan Yiu , Leung Tak Yeung , Li Tin Chiu 
Published: June 2021

Evaluating oocyte quality in assisted reproductive technology (ART) is essential to ensure a healthy pregnancy. Currently, morphological assessment on oocyte is applied to predict oocyte and embryo development potential. The method is limited and may not provide an accurate assessment of oocyte quality. Human polar body (PB) is the byproduct of an oocyte maturation. The advent of PB karyotyping has served as an indirect genetic analysis of oocytes and provided metrics of embryonic potential. This prompts the idea of oocyte genome interrogation by studying PB genome, and a recent study has shown transcriptome of PB could accurately reflect the transcriptome landscapes of the sibling oocyte. Yet the epigenetic dynamics of PB and oocyte remains elusive. Here we hypothesized that the methylome profile of PB could be representative of oocyte methylome.To reveal the epigenome information on PB and oocyte, we performed single‐cell whole genome bisulfite sequencing (scWBS) on mouse metaphase II (MII) oocytes and the associated PBs. Overall, we detected 1,653,985 CpG sites in the oocyte and 55,941 CpG sites in the PB respectively. The genome‐wide methylation level of CpG sites in PB was 73.56%, compared to 54.85% in oocyte. To examine if PB methylome could predict oocyte methylome landscape, all CpG sites covered with more than 3 reads and a window size of 2,000 bp were used to calculate the correlation of methylation level between PB and its sibling oocyte. They showed a moderate Pearson's correlation coefficient (r=0.5295), which was consistent with published data. We also calculated the correlation of methylation level in promoter region, but to our surprise, the correlation was weak (r=0.209). These results suggested that global methylation level in the mouse PB could not be applied to predict it sibling oocyte methylome. In summary, our preliminary data suggests that the correlation of global methylation level between mouse oocyte and its sibling oocyte is not as high as expected, but this conclusion need to be further confirmed by analyzing more samples.Support or Funding InformationCollaborative Research Fund, Hong Kong Research Grant Council.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Activated mesothelial cells in pleural fluid after lung resection and transplantation
Authors: Kienzle Arne , Servais Andrew B , Alexandra Ysasi B , Gibney Barry C , Cristian Valenzuela D , Wagner Willi L , Ackermann Maximilian , Mentzer Steven J 
Published: June 2021

ObjectivesThe mesothelium, the surface layer of the heart, lung, bowel, liver and tunica vaginalis, is a complex tissue implicated in organ‐specific diseases and regenerative biology. An open question is the mechanism of mesothelial repair after injury. Previous observations indicated that the seeding of denuded mesothelium by free floating mesothelial cells may contribute to mesothelial healing.Material and MethodsIn this study, the pleural fluid of 54 patients after lung resection or transplantation was analysed. Flow cytometry was employed to study the cellular composition of post‐surgical pleural fluid. We used histologically validated mesothelial markers (CD71 and WT1) to estimate the prevalence of mesothelial cells.ResultsThe viability of pleural fluid cells approached 100% indicating that the cells were not just dying exfoliated cells. Leukocytes and mesothelial cells were identified in the pleural fluid within the first week after surgery. The leukocyte concentration rapidly declined after postoperative day 1. In contrast, mesothelial cells, identified by CD71 and WT1, peaked on postoperative day 3. Based on optimal sampling and average cell size, we estimate that the post‐operative day 3 pleural fluid contains sufficient numbers of activated mesothelial cells to cover several cm2 of denuded mesothelium. The broad expression of CD71 molecule in postoperative pleural fluid suggests that many of the free‐floating non‐leukocyte cells were activated or proliferative mesothelial cells.ConclusionWe demonstrated that pleural fluid post lung surgery is a source of mesothelial cells; most of these cells appear to be activated or proliferative mesothelial cells. The observed peak of mesothelial cells on postoperative day 3 is consistent with a potential reparative role of free‐floating mesothelial cells after pulmonary surgery. The high viability of these cells and the convenient drainage chambers used after lung surgery suggests an opportunity for further in vitro studies of these free‐floating mesothelial cells.Support or Funding InformationSupported in part by NIH Grant HL94567, HL134229, HL007734, CA009535, ES000002, the German Research Foundation (SFB1066), and a Boehringer‐Ingelheim Fonds Travel Grant.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Dengue Fever: the Next Global Killer
Authors: Raynes Edilberto A. , Glymph Kelly , Coker Karen , Agazuma Keshia , Michaels Natalie , Menchavez Melinda Roca , Raynes Janika Ziarah Rellama 
Published: June 2021

The purpose of the study is to review the epidemiological aspects of the dengue fever infection. The infection is caused by dengue viruses (DENV), which have four different serotypes and antigenically distinct. The DENV is transmitted by a vectorborne day biting mosquito, Aedes agypti. The clinical spectrum ranges from dengue fever to dengue hemorrhagic fever. Based on our review from the World Health Organization, Centers for Diseases Control and Prevention, as well as from other studies, the disease is still more endemic in the Southeast Asia and Western Pacific regions with an estimate of 300 million infections annually, mostly affecting children. Factors that contribute to the emergence of DENV infection worldwide include substandard living conditions, virus evolution, lack of vector control programs, and international travelers. The best measure of DENV control is prevention by increasing awareness of the public through coordinated outreach programs to the community coordinated by various stakeholders. There are still no available vaccines and specific medications to cure. A multidisciplinary collaboration needs to be mobilized to combat the vector.Support or Funding InformationNoneThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Modulation of striatal dopamine release by nicotinic receptors in adolescent and adult rats
Authors: Pitts Elizabeth , Stowe Taylor , Fennell Ashley , Sexton Lacey , Ferris Mark 
Published: June 2021

Adolescence is a developmental period characterized by increased vulnerability to substance use and dependence. However, mechanisms mediating this vulnerability are not well understood. Previous work has shown that locomotor responses in a novel environment predict acquisition of nicotine and cocaine self‐administration in adult rats, with high‐responders (HR) acquiring faster and at lower doses than low‐responders (LR). Additionally, adult rats with higher vulnerability have more sensitive nicotine acetylcholine receptor (nAChR) modulation of striatal dopamine release to phasic firing‐like stimulation, which is known to be important in acquisition of self‐administration. Here we examined how antagonism of nAChRs altered dopamine release in the nucleus accumbens core in adolescent and adult rats using fast scan cyclic voltammetry. We found that non‐selective antagonism of nAChRs, by mecamylamine (2 uM) or a desensitizing dose of nicotine (500 nM), increased dopamine release in HRs to stimulation that models phasic dopamine release, but suppressed dopamine release in LR rats. Further, we report a‐conotoxin PIA (100 nM), an a6‐selective antagonist, produced similar effects as the non‐selective antagonists, indicating that facilitation of dopamine in the HR rats is mediated by a6‐containing nAChR. When dopamine release in adolescent rats was tested under the same parameters, nAChR modulation of dopamine release was similar to HR adult rats, with non‐selective and a6‐selective antagonists facilitating dopamine release following phasic firing‐like stimulation. This suggests a role for a6‐containing nAChR modulation of striatal dopamine release in mediating vulnerability to drug abuse.Support or Funding InformationThis work is supported by NIDA grant R00 DA031791 awarded to MJFThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Synthesis and Evaluation of Symmetrical and Unsymmetrical Diacyl Ureas, Acyl Urea/Carbamate/Thiocarbamate Derivatives and their Evaluation for FAAH inhibition
Authors: El‐Alfy Abir , Johnson Jacklyn , Hernandez Anolan Garcia , Grooms Gregory , Stec Jozef 
Published: June 2021

Fatty acid amide hydrolase (FAAH) is a serine hydrolase enzyme that metabolizes various lipophilic transmitters, including oleamide, anandamide, and 2‐arachidonyl glycerol. These neurotransmitters are part of the endocannabinoid system (ECS) that comprises a neuromodulatory network involved in regulation of various physiological functions, including appetite, pain, reward, motor control, memory, and mood. Previous studies have shown that enhancing the ECS offers a potential therapeutic target for various psychiatric disorders. An FAAH inhibitor provides indirect modulation of the system, with the added advantage of avoiding undesirable adverse effects associated with the direct receptor agonists. The objective of this study was to synthesize various oleamide analogs and evaluate them for FAAH inhibition. A total of fifty one compounds (1–51) were synthesized using a one‐pot two‐step synthetic scheme. All compounds were evaluated in the in vitro FAAH inhibition assay using human recombinant FAAH enzyme, at 2–100 uM concentrations. Of these compounds, ten analogs showed >50% FAAH inhibition activity at the 50 uM concentration. These compounds serve as leads for structure activity relationship studies to optimize the inhibitory activity and to help design potent and effective FAAH inhibitors to be evaluated in vivo in various animal models of neuropsychiatric disorders.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Targeted downregulation of MYC through G‐quadruplex stabilization: a novel therapeutic approach for breast cancer and lymphoma
Authors: Chang Katarina T. , Hao Taisen , DeSouza Harriet EJ. , Brooks Tracy Ann 
Published: June 2021

MYC, a basic helix‐loop‐helix/leucine zipper transcription factor, is an enigmatic protein with over 30,000 potential binding sites in the human genome, 10–15% of which are generally bound at any one time. It was one of the first proto‐oncogenes to be described and is ultimately disregulated in most tumor types and stages, including estrogen receptor (ER)‐positive breast cancer and non‐Hodgkin's lymphoma. Decreased MYC expression has been shown to significantly impact tumor viability while offering a notable therapeutic window and overall safe profile. As we and other groups have shown, stabilization of the higher order genomic structure – the G‐quadruplex (G4) – in the MYC promoter is an established approach to decreasing transcription and facilitating tumor lysis. We have pioneered a DNA interference (DNAi) approach to take advantage of the “druggability” of the DNA structure, and have previously demonstrated the specificity and efficacy of oligonucleotide (ODN)‐mediated stabilization of the predominant G4 structure within the MYC promoter. In the current report, we further optimize the DNAi, including the evaluation of different ODN lengths, for specifically stabilizing the MYC promoter G4 (as demonstrated by EMSA and chemical footprinting) and modulating promoter activity. The lead DNAi (A‐18) demonstrates anti‐cancer activity in RAJI and CA46 Burkitt's lymphoma cells, and in ER+ MCF‐7 breast cancer cells. Moreover, A‐18 enters the nuclei of cancer cells, where it binds the G4‐forming region of the MYC promoter, in an inducible manner. This clamp has potential as a novel DNAi therapeutic. It is being further explored for its ability to sensitize cancer cells to chemotherapeutic agents, and its formulation for delivery in nanotherapeutic vehicles.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Characterization of the novel anti‐cancer therapeutic ONC201 and related analogs as non‐competitive antagonists of the D2 dopamine receptor
Authors: Cuoco Caroline A. , Free R. Benjamin , Willette Blair K. , Day Marilyn M. , Lane J. Robert , Allen Joshua E. , Sibley David R. 
Published: June 2021

ONC201 is the first member of a new class of anti‐cancer small molecules called imipridones to be investigated in clinical trials for select advanced cancers. The anti‐cancer properties of the parent compound were first discovered in a phenotypic screen as a p53‐independent inducer of the immune cytokine TRAIL and tumor cell death. Tumor cell signaling studies revealed that ONC201 causes a dual inactivation of Akt/ERK that drives Foxo3a‐mediated TRAIL gene induction. Recent studies identified that ONC201 also selectively antagonizes D2‐like dopamine receptors (D2R, D3R, D4R) at therapeutically relevant concentrations. Notably, malignant overexpression of the D2R occurs in a variety of cancers and its antagonism imparts pro‐apoptotic and anti‐proliferative effects in tumor cells. In the current study, we sought to characterize the pharmacological properties of ONC201 and several novel analogs (ONC206 and ONC213) on D2‐like receptors. Both functional signaling (β‐arrestin recruitment and cAMP accumulation) and radioligand competition binding assays were employed. Radioligand binding assays with [3H]‐methylspiperone determined that these compounds bind to D2‐like receptors with low μM affinity, consistent with their potencies for anticancer activities. When the compounds were tested in β‐arrestin recruitment assays (D2R, D3R, and D4R) and cAMP accumulation assays (D2R and D4R), all analogs were determined to be antagonists with no measurable agonist efficacy. Importantly, a resolved enantiomer of ONC201 that showed no anti‐cancer activity was found to be inactive in blocking the D2R. To gain further insight into the mode of action of ONC201 and analogs at the D2R, Schild‐like curve shift assays were performed in using the functional assays, where increasing concentrations of compound are used to shift the dopamine concentration‐response curve. Increasing concentrations of all compounds caused both a rightward shift in the dopamine concentration‐response curve and a depression of the maximum response. These data are consistent with a non‐competitive mode of action and could be fitted with an operational model of allostery. These analyses revealed a predominant modulatory effect upon dopamine efficacy and a smaller effect on dopamine potency. Further studies will aim to elucidate the nature in which these analogs interact with D2R binding pockets through site‐directed mutagenesis. Understanding the pharmacological profile of ONC201, including different signaling paradigms, may lead to a better understanding of its mechanism for anticancer targeting.Support or Funding InformationNINDS IRPThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Angiotensin ll Type 2 (AT2) Receptors: Novel Target in Asthma
Authors: Kurade Mangesh , Patel Mehaben , Rajalingam Sahith , Siddiquee Armaan , Narke Deven , Ponnoth Dovenia S. 
Published: June 2021

Angiotensin ll (Ang ll) is produced locally in the lungs and may potentiate airway responsiveness in asthmatic patients. Ang ll induces its effects by activating two GPCR subtypes: AT1 and AT2. This lab has previously found that AT1 antagonist losartan reduces airway inflammation and reactivity. The AT2 receptors counterbalance the effects of AT1 and are known to be anti‐inflammatory. However, it is not known if AT2 receptors have any effects in asthma. We studied the effects of AT2 agonist novokinin and antagonist PD 12339 administered in vivo in a mouse model of asthma. Mice were divided into control (non‐allergic; CON) and allergen sensitized‐challenged (SEN) groups, and were sensitized i.p. on days 1, 6 with 0.2μg ovalbumin (OVA) followed by 5% OVA aerosol challenges on days 11–13. Whole body plethysmography (measuring airway responsiveness as enhanced pause, Penh) and bronchoalveolar lavage (BAL) studies were performed. Methacholine (MCh; 48mg/ml) produced significantly higher airway responsiveness in allergic mice compared to control (563.71±40% in SEN vs. 208.79±20.84% in CON, p<0.05). However, novokinin (i.p. 0.3mg/kg) treated SEN mice had significantly attenuated MCh‐indcued airway responsiveness (563.71±40% in SEN vs. 252±11% in SEN+Novokinin, p<0.001). The AT2 antagonist PD 12339 (i.p.5mg/kg) significantly increased MCh airway responsiveness (563.71±40% in SEN vs. 757±30% in SEN+PD 12239, p<0.05). Differential BAL cell analysis showed novokinin also decreased eosinophils (221±21 in SEN vs. 122±18 in SEN+PD 12239, p<0.001), while PD 12239 had no effect on eosinophils (245± 16 cells in SEN+PD 12339). Our data suggests that activation of AT2 receptors may attenuate airway reactivity and inflammation in our model of asthma.Support or Funding InformationLong Island University start‐up funds (DSP)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Theoretical Considerations of Novel Nanocarbon Onion‐like Fullerene Material (NOLF) in Mitochondrial Quantum Processes, Mediation of Disruptive Perturbation, and Maintenance of Intracellular Quantum Electrodynamics
Authors: Bourassa Daniel J. , Tulp Orien L. , Einstein George P. 
Published: June 2021

Medical research into fullerenes, though still currently in its early phases of discovery, has revealed novel applications due to their unique characteristics and compatibility with living cells. This has produced some exciting and potentially promising medical applications. Research supports evidence of enhanced ROS protection, anti‐inflammatory action, HIV protease inhibition, mitochondrial SOD mimetic, and possible longevity benefits among other uses. Fullerenes are increasingly being modified or functionalized as transporter molecules, phototherapy agents, and even considered for primary treatment options in a wide array of diseases, including cancer. However, there is much we don't know. The six‐carbon aromatic ring is among the most electrodynamically stable carbon structures and essential to the known biochemistry of life due to dense pi cloud properties. All fullerenes are composed largely of aromatic six carbon rings. Nanocarbon onion‐like fullerene material (NOLF) all have the basic structure C60n2 and derive most of their electrodynamic properties from their outer two shells. This creates a very large and diffuse but dense pi cloud that seems to share C60s biological compatibility and benefits but potentially offers more due to multi‐shell electrodynamics, diamagnetism, and increased capacitance characteristics. These mechanisms help explain how NOLF assists mitochondria to resist disruptive perturbations and restore homeostasis in disease states as well as maintain and regulate it in health. With interest increasing in the cellular electrodynamics, ultra‐weak photonic emission, electromagnetic resonance, and the role of the quantum cell in health and disease; the electrodynamic properties of NOLF and observed biological effects merit greater attention. We present a theoretical basis, derived from current research, for the influence of NOLF in the enhancement of mitochondrial quantum processes, mediation of disruptive perturbation, and assistance in maintenance of intracellular quantum electrodynamics in chronic degenerative disease and cancer, and suggest future research to investigate these proposed quantum effects in mitochondria and cells.Support or Funding InformationSupport from Institutional ResolurcesThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
BPC 157 Rescues NO‐System in Perforated Stomach and Caecum
Authors: Drmic Domagoj , Vidovic Tinka , Vlainic Josipa , Samara Mariam , Gojkovic Slaven , Krezic Ivan , Jeyakumar Jerusha , Bilic Zdenko , Seiwerth Sven , Sikiric Predrag 
Published: June 2021

AimWe focused on perforated defect in stomach and caecum, and NO‐tissue levels in rats and the therapy with the stable gastric pentadecapeptide BPC 157. Effective in perforated stomach lesion and perforated caecum lesion as well as ischemic colitis, ischemia and reperfusion, BPC 157 rapidly activates vessels “running” toward the perforated defect (stomach perforation (Gastroenterology 2017; 152, Issue 5, Supplement 1, S889–S890; Gastroenterology 2017; 152, Issue 5, Supplement 1, S890–S891) or to bypass vessel obstruction (ischemic colitis)(World Journal of Gastroenterology, in press, 2017) and largely attenuates lesions course.MethodsAt 15 minutes post‐injury, we determined nitric oxide (NO) levels in stomach caecum tissue samples using the Griess reaction (Griess Reagent System, Promega, USA). Sulfanilamide was added to the homogenized tissue, incubated and then N‐1‐naphthylethylenediamine dihydrochloride was added. The Griess reaction is based on diazotization reaction in which acidified nitrite reacts with diazonium ions and in a further step are coupled to N‐1‐naphthylethylenediamine dihydrochloride forming chromophoric azo derivate. Absorbance was measured at 540 nm, using sodium nitrite solution as standard. NO levels are reported in μmol/mg protein. Proteins were determined using the commercial kit (BioRad Protein DR Assay Reagent Kit, USA). Medication was bath (BPC 157 10 ug, 10 ng/kg/1ml bath/rat; equivolume saline (controls)) at the ligated perforated injury, in stomach or caecum, at 1 min after perforated injury induction.ResultsStomach. In the early term, we noted fewer NO‐levels in rats underwent stomach perforation, but a reversal with BPC 157 administration, and thereby, NO levels like in the healthy appear in rats with perforated stomach underwent BPC 157 medication (Fig. 1). Caecum. Likewise, NO level assessment demonstrated a drop in level in rats which underwent caecum perforation, but the NO values in rats with perforated caecum which underwent BPC 157 medication were similar to the NO‐levels in healthy rats (Fig. 2).ConclusionsRapid activation of vessels “running” toward the perforated defect (perforated defect healing and attenuated bleeding, counteraction of free radicals formation previously described by BPC 157 application, occurs with the parallel rescue of the NO‐system in the both of the perforated tissues (stomach perforation (Gastroenterology 2017; 152, Issue 5, Supplement 1, S889–S890; caecum perforation (Gastroenterology 2017; 152, Issue 5, Supplement 1, S890–S891)).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.