bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of Tobacco Users in Creating an Educational Intervention to Promote Oral Health
Authors: Chawla Sudeep , Einstein George P. , Tulp Orien L. 
Published: June 2021

The purpose of this study was to characterize smoking behaviors amongst individuals of various socioeconomic status, to assess the need to develop an educational program that addresses the failure of getting treatments for diseases that stem from tobacco related products. Further, we wished to identify the target populations that might be the most suitable to be recruited in such a program for behavioral intervention and consultation by an oral health professional with a goal to to dissuade individuals from smoking and other tobacco use. Consuming tobacco in form of cigarettes, but also in more ‘artisanal’ forms like cigars and pipes as well as the current trend to ‘vaping’ or even consuming entirely smokeless tobacco are behaviors that are ultimately detrimental to the oral and subsequent physical health of individuals. Socioeconomic status has been negatively correlated with the engagement in such unhealthy behaviors, thereby potentially burgeoning society with increased treatment costs while suggesting that better access to public resources might be a viable way to reduce tobacco consumption across the socioeconomic strata in the future.MethodsIn a retrospective study, adult patients at NSU Dental School's Department of Oral Diagnosis were asked about their smoking behavior and several other demographic details, including age, gender, educational status and smoking history using an Axium questionnaire. Results indicated there was a slight prevalence of non‐smokers vs. smokers among the participants, with a few individuals preferring smokeless tobacco or electronic cigarettes. The prevalence or non‐smokers vs. smokers was reflected across the majority of demographic categories, with the exception of young age, old age, middle to low income and either low or the highest degree of education.ConclusionThese results are sufficient to select a first cohort of individuals who were younger and in a lower socioeconomic category to participate in a consultation/behavioral intervention program for tobacco users with low vs. high socioeconomic status.Support or Funding InformationSupport from Institutional ResourcesThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effect of Pistachios and Mixed Nuts on Bone Density and Osteogenic Gene Expression in Young Male Rats
Authors: Wickman Brooke E. , Rochester Eric , Hauffe Laura , Kern Mark , Hong Mee Young , Liu Changqi , Hooshmand Shirin 
Published: June 2021

Nut consumption has beneficial health effects that include reducing the risk of cardiovascular disease, improving blood lipid profiles, and reducing oxidative damage. Nuts contain several nutrients that are involved in the maintenance and development of bone such as calcium, protein, fatty acids, and various phenolic antioxidants. To investigate the effect of nuts on bone health, thirty 21‐day‐old Sprague Dawley rats were randomly assigned to one of three isocaloric diets containing pistachios (8.1% w/w), mixed nuts (7.5% w/w), or a control diet for 8 weeks. True bone densities of tibias and femurs were measured using Archimedes' principle, and areal bone densities of total body without heads were measured using dual‐energy X‐ray absorptiometry (DXA). Femoral mRNA expression of various genes including RANK, RANKL, and OPG were also assessed. True densities of the tibias were significantly different among groups (p<0.03). Post hoc analyses indicate that tibial true densities of rats in the pistachio group were greater than tibial true densities of rats in the control group (p<0.05, 95% CIΔ 0.001 to 0.092). There was no significant difference between the tibial true densities of the rats in the pistachio group and the mixed nut group nor in the control group and the mixed nut group. There was no significant difference in the femoral true density or the whole body DXA bone mineral density among groups. Though there was a higher tibial true bone density in the pistachio group compared to that of the control group, there were no significant differences in the genes presumed responsible for these changes. It can be concluded that pistachio intake may have beneficial effects on bone density. The potential mechanism of action should be further investigated.Support or Funding InformationAmerican Heart AssociationThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Role of N‐Methyl‐D‐Aspartate Receptor (NMDAR) in Co‐morbid Schizophrenia and Substance Abuse
Authors: Desai Rajeev I. , Puhl Matthew D. , Coyle Joseph T. 
Published: June 2021

Both schizophrenia (SZ) and substance abuse (SA) exhibit significant heritability. Moreover, N‐methyl‐D‐aspartate receptors (NMDARs) have been implicated in the pathophysiology of both SZ and SA. We hypothesize that the high prevalence of co‐morbid SA in SZ is due to dysfunction of NMDARs caused by shared risk genes. We used transgenic mice with a null mutation of the gene encoding serine racemase (SR), the enzyme that synthesizes the NMDAR co‐agonist D‐serine, to mimic an established genetic risk factor for SZ. We determined the effect of NMDAR hypofunction resulting from the absence of D‐serine on motivated behavior using intracranial self‐stimulation (ICSS) and neurotransmitter release in the nucleus accumbens using in vivo microdialysis. Compared to wild‐type mice (WT), SR−/− mice exhibited similar baseline ICSS thresholds but were less sensitive to the threshold‐lowering (rewarding) and the performance‐elevating (stimulant) effects of cocaine. While basal dopamine (DA) and glutamate release were elevated in the nucleus accumbens of SR−/− mice, cocaine‐induced increases in DA and glutamate release were blunted. γ‐Amino‐butyric acid (GABA) efflux was unaffected in the SR−/− mice. Together, these findings suggest that the impaired NMDAR function and a consequent decrease in sensitivity to cocaine effects on behavior are mediated by blunted DA and glutamate responses normally triggered by the drug. Preliminary data from ongoing behavioral studies in SR−/− and WT mice also show a decreased sensitivity to nicotine's behavioral effects. Projected to humans, NMDAR hypofunction due to mutations in SR or other genes impacting glutamatergic function in SZ may render abused substances less potent and effective, thus requiring higher doses to achieve a hedonic response, resulting in elevated drug exposure and increased dependence/addiction.Support or Funding InformationThis research was supported by NIH grant RO1MH51290‐18 to JTC, DA031231 K01 NIH/NIDA grant to RID, and a NARSAD Young Investigator Award to MDP.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Studies on identification of genes associated with neuronal memory using of rat hippocampal neurons
Authors: Opoku Ruth , Ahmed Ijaz , Patwary Mohsin , Nur‐e‐Kamal Alam 
Published: June 2021

We have previously demonstrated that extracellular matrix (ECM) proteins facilitate neurite extension of rat cerebellar granule neurons (CGNs) in culture. We have also identified the functional domain(s) of these proteins involved in neurite outgrowth. Hippocampal neurons play an important role of storing memory in animals. We propose a hypothesis that “hippocampal neurons can be used to identify genes associated with storage of memory in animals”. In this report we developed a ECM‐coated culture surface to growth primary rat hippocampal neurons and determined their neurite outgrowth. We have also compared the neurite outgrowth of CGN and hippocampal neurons. Cerebellar granule neurons, cortical neurons (CN), and hippocampal neurons were plated onto the cover slips coated with extracellular matrix proteins (laminin‐1, fibronectin, and collagen) at a density of 105 neurons per ml. The neurons were allowed to extend neurites for 24 hrs in NBM/B27/KCl. The extent of neurite outgrowth was then determined using carboxyfluorescein diacetate (CFDA) labeling. Images of the cultures were captured and analyzed with the NIH Image software. A sample of 100 neurons with well‐defined processes were studied for each condition. Laminin and fibronectin‐coated surfaces induced neurite outgrowth of Cerebellar granule neurons, cortical neurons, and hippocampal neurons. It was found that collagen stimulates neuirte outgrowth of CGN, while collagen inhibited neurite outgrowth of hippocampal neuron. We have developed a condition for culture of hippocampal neurons. By immunostaining, immunoblot, and RT‐PCR analysis we found alteration of expression of some genes genes involved in neurite outgrowth, Results of these studies with be presented in this report. These hippocampal neurons will be used to apply different types of stimuli and identify genes involved in saving memory in neurons. Identification of genes associated with saving memory might be useful in developing a therapy for neurological disorders including Alzheimer's, Parkinson's diseases.Support or Funding InformationNIH‐RISEThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Five Different Phosphorylation Sites in the C‐Terminal regulate a1b‐Adrenergic Receptor Signaling and Regulations
Authors: Hernández David Alejandro 
Published: June 2021

The G protein‐coupled receptors (GPCRs) transmit a variety of signals across the cell membrane and regulate cellular activity via the intermediary role of guanine nucleotide regulatory proteins (G proteins). Among these receptors, the a1B‐Adrenergic (a1B‐AR) receptor mediates the effects of catecholamines, like epinephrine and norepinephrine, through coupling to Gq. The activation of the a1B‐AR causes polyphosphoinositide hydrolysis catalyzed by phospholipase C (PLC), generating inositol trisphosphate and diacylglycerol, which together lead to calcium signaling and protein kinase C (PKC) activation. Subsequently, receptors are phosphorylated, triggering their desensitization and internalization, a process mediated by members of the G proteins‐coupled receptor kinases (GRK) family and/or by PKC.It is currently known the a1B‐AR is phosphorylated in two separate groups of serine residues in the carboxyl terminal tail, one by PKC (S396 and S402) and one by GRK (S406, S410 and S412) during the desensitization and internalization of the receptor. The mutation of these residues prevents agonist induced desensitization and blocks the receptor internalization into the plasma membrane.Because the role of these specific sites remains unknown in different down‐process of the a1B‐AR, we investigated the importance of phosphorylation by PKC and GRK in calcium desensitization signal, mitogen activated protein kinases (MAPK) pathway and receptor phosphorylation. To achieve this,, we generated three site specific mutants of the a1B‐AR in which the serine residues phosphorylated by the two kinases were mutated to alanine, alone or in tandem. We found that any of these mutations in the phosphorylation sites produces changes in the heterologous desensitization of the receptor detected by intracellular calcium response and in the activation of the MAPK, when compared to the wild type. Finally, we obtained clear differences in the phosphorylation pattern of each mutant during noradrenaline stimulation.Support or Funding InformationPartially supported by Grants from CONACYT (253156 and 882) and DGAPA (IN200915).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Different Phosphorylation Sites Regulate α1D‐Adrenergic Receptor Function
Authors: Rosas Gabriel Carmona 
Published: June 2021

Human α1D‐adrenergic receptors (α1D‐AR) are seven transmembrane‐spanning proteins that mediate the actions of noradrenaline in homeostasis maintenance as well as the physiology of hypertension and benign prostatic hyperplasia. Although several studies have demonstrated that α1D‐AR is a phosphoprotein, the phosphorylation sites and the specific roles that they play in the function and regulation of this receptor, are currently unknown. Using a combination of in silico analysis, mass spectrometry and site directed mutagenesis, we identified for the first time distinct phosphorylation patterns on α1D‐AR during noradrenaline (homologous) and non‐related agents‐mediated (heterologous) desensitization. We were able to identify that G protein‐coupled receptor kinase‐2 (GRK2) and protein kinase C α/β (PKC α/β) phosphorylate α1D‐AR during these processes. Phosphorylation of the receptor's intracellular domains, such the intracellular loop 3 or the carboxyl tail, was enough to altered calcium desensitization signals, mitogen activated protein kinases (MAPK) pathway and regulate receptor internalization, suggesting that modular regulatory mechanisms heavily rely on the phosphorylation bar code and the receptor's intracellular domains.Subsequently, we generated six specific non‐phosphorylatable α1D‐AR mutants to delve into the functions of the phosphorylation sites located only at the receptor's carboxyl tail. We found clear differences in the phosphorylation pattern of each mutant during noradrenaline and non‐related agents‐stimulation. Moreover, we analyzed the activation of the MAPK and AKT pathways as well as intracellular calcium mobilization. Modification of any of these phosphorylation sites altered the response when compared to the wild type, but no clear differences were observed among the different α1D‐AR mutants. Interestingly, seven specific phosphorylation sites clustered into two groups in the carboxyl tail, regulate the α1D‐AR subcellular location. This was confirmed when these two clusters were mutated with negative charged residues and the α1D‐AR was located again at the plasma membrane.These data suggest that different phosphorylation sites located in the carboxyl tail regulate the α1D‐AR functions and regulation at different levels. This knowledge highly contribute to unveil new strategies to improve current pharmacological treatments and to avoid drug side effects during sustained administration.Support or Funding InformationPartially supported by Grants from CONACYT (253156 and 882) and DGAPA (IN200915).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Amyloid Beta Peptide Modulates the Signaling Property of Chemokine‐like Receptor 1
Authors: Ye Richard D. , Zhang Shuo , Liao Dan , Gong Hao 
Published: June 2021

OBJECTIVEAmyloid beta peptides (Aβ) are the main constituents of the amyloid plaques found in the brains of Alzheimer patients. While Aβ is proinflammatory and contributes to the development of Alzheimer's disease, its signaling property remains unclear. The present study investigates how Aβ modulates signaling of one of its receptors, the chemokine‐like receptor 1 (CMKLR1, ChemR23).METHODSCells expressing CMKLR1 were incubated with Aβ42 before stimulation with another agonist of the CMKLR1, the C9 peptide. Calcium mobilization, cAMP inhibition and MAP kinase activation were measured. Intramolecular FRET was determined using CMKLR1 constructs containing an ECFP attached to the C‐terminus.RESULTSBinding of both Aβ42 and the C9 peptide induced CMKLR1 internalization, but only the Aβ42‐induced receptor internalization involved clathrin‐coated pits. Likewise, Aβ42 but not C9 stimulated β‐arrestin2 translocation to plasma membranes. A robust Ca2+ flux was observed following C9 stimulation, whereas Aβ42 was ineffective even at micromolar concentrations. Despite its low potency in calcium mobilization assay, Aβ42 was able to alter C9‐induced Ca2+ flux with potentiation at concentrations as low as 0.1 – 1 nM. However, at higher concentrations the effect was diminished. Similar effects were seen with the C9‐induced ERK phosphorylation but the dose curve was different from that of Ca2+ flux and cAMP inhibition, suggesting a reciprocal regulatory mechanism. Intramolecular FRET assay confirmed that Aβ42 modulates CMKLR1 rather than its downstream signaling pathways.CONCLUSIONThese findings suggest that long‐term exposure to Aβ42 may alter the signaling properties of its receptors, thereby influence the pathology of Alzheimer's disease. The reciprocal regulation of CMKLR1 by Aβ provides a novel mechanism by which a ligand dose‐dependently modulates the response of its receptor to another ligand.Support or Funding InformationSupported by grants SRG2015‐00047‐ICMS‐QRCM and MYRG2016‐00152‐ICMS‐QRCM from University of Macau and by grant 31470865 from NSFC.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Development of a comprehensive profiling method for regulatory lipid mediators using UPLC‐MS/MS
Authors: Yang Jun , Wan Debin , Sun Jia , Hammock Bruce D. 
Published: June 2021

The regulatory lipid mediators are biologically active metabolites derived from polyunsaturated fatty acids such as the metabolites by cyclooxygenases, lipoxygenases, and cytochrome P450 enzymes. These pathways represent over 75% of pharmaceutical in mass in the world. By measuring endogenous metabolic responses to various environment stimulus, pathological processes and dietary supplements, lipidomics/metabolomics provide the most useful information about human responses. The knowledge gained from this type of research is very useful for many research fields including biomarker discovery, biotechnology advancement, discovery of novel biochemical mechanism, and assessment of clinical effectiveness.We developed a sensitive and comprehensive profiling method for the regulatory lipid mediators covering more than 150 lipid mediators including prostaglandins, leukotrienes, epoxy fatty acids, dihydroxy fatty acids, specialized pro‐resolving mediators, endocannabinoids, nitro‐fatty acids, poly‐unsaturated fatty acids and the trace for major species of phospholipids.Support or Funding InformationThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
A Key Role of Soluble Epoxide Hydrolase in the Pathogenesis of Parkinson's Disease
Authors: Ren Qian , Ma Min , Yang Jun , Nonaka Risa , Yamaguchi Akihiro , Ishikawa Kei‐ichi , Kobayashi Kenta , Murayama Shigeo , Saiki Shinji , Akamatsu Wado , Hattori Nobutaka , Hammock Bruce D. , Hashimoto Kenji 
Published: June 2021

Parkinson's disease (PD) is a chronic and progressive neurodegenerative disorder. Although there are many medications available to treat the symptoms in PD patients, these medications cannot reverse the progress of the disease. The soluble epoxide hydrolase (sEH) plays a key role in the inflammation which is involved in the pathogenesis of PD. The present study was undertaken to examine whether sEH plays a role in the pathogenesis of PD. MPTP (1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine)‐induced dopaminergic neurotoxicity in the striatum and substance nigra (SNr) of mice could be attenuated by subsequent repeated administration of TPPU, a potent sEH inhibitor. Furthermore, deletion of sEH gene protected against MPTP‐induced neurotoxicity in the striatum and SNr. Moreover, the treatment with TPPU or deletion of sEH gene attenuated and protected the MPTP‐induced ER stress and oxidative stress in the striatum. In addition, expression of sEH protein in the striatum from MPTP‐treated mice and patients with dementia of Lewy body (DLB) was higher than controls. Overexpression of sEH after AAV injection into the striatum significantly enhanced MPTP‐induced neurotoxicity in this region. Interestingly, expression of sEH mRNA in the neuron from iPS cells from PD patients was higher than that of healthy control subjects, and treatment with TPPU could protect against neurotoxicity in the neurons from iPS cells of PD patients. The present results suggest that sEH plays a key role in the pathogenesis of PD, and that epoxy fatty acids, their mimics as well as sEH inhibitors could be potential therapeutic or prophylactic drugs for PD.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Identification of Structural‐Activity Features of Long Chain Polyunsaturated Fatty Acid Epoxides in Angiogenesis
Authors: Betts Rebekah Marie , Lee Kin Sing , Cinelli Maris , Karchall Lalitha , Luca Joe , Confer Nick 
Published: June 2021

The cytochrome P450‐derived fatty acid epoxides are bioactive lipids with regulatory roles in a wide range of homeostatic and pathophysiological events. These lipid mediators are metabolized efficiently by the mammalian soluble epoxide hydrolase enzyme (sEH) to corresponding 1,2‐diols. Inhibition of sEH has been shown to be beneficial to human health via increasing concentrations of a variety of short‐lived epoxylipids in vivo (2). Identifying the most potent polyunsaturated fatty acid (PUFA) epoxide metabolites will provide insight on the effects of sEH inhibition. Recent studies have shown that the omega‐6 epoxyeicosatrienoic acids (EETs) from arachidonic acid are pro‐angiogenic, while the omega‐3, docosahexaenoic acid (DHA)‐derived epoxydocosapentaenoic acids (EDPs) inhibit angiogenesis, tumor growth, and metastasis (1). Given these findings, we are interested in exploring the roles of various long chain PUFA epoxides in angiogenesis. We tested a library of omega‐3 and omega‐6 epoxides in a newly developed high‐throughput tube formation assay and found their effects are regiospecific and stereospecific; Of note, the 19(S),20(R)‐EDP stereoisomer was a less effective inhibitor of endothelial cell tube formation than its respective racemic mixture. Here, we report the angiogenic activities of diverse omega‐3 and omega‐6 fatty acid epoxides that could be present in mammals from the diet, including the less explored epoxides from both omega‐3 and omega‐6 docosapentaenoic acid (DPA). We will discuss the structure‐activity features of the most potent epoxide species and also present methodology to synthesize and purify the regioisomers and stereoisomers of each series of epoxides. Ultimately, understanding activities of sEH substrates in specific regulatory environments will guide development of targeted sEH modulators that promote the beneficial effects of PUFA metabolites in human health and 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.