bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Ultrafine Nano‐zinc Particles on Cardiac Structure and Function in Myocardial Infarction Mice
Authors: Huang Yufan , Huo Yunlong 
Published: June 2021

ObjectiveWe aimed to illustrate the association between ultrafine nano zinc particles inhalation and cardiac structure and function in myocardial infarction (MI) mice.Method6‐week‐old ICR mice were divided into three groups randomly: sham group, MI group and MI exposure group, 12 mice in each group. We preformed LAD ligation operation in MI group and MI exposure group. After postoperative two weeks MI exposure mice were put into ventilation chamber which filled with 500ug/m3 ultrafine nano zinc particles for 6 hours per day, while MI group mice and sham group mice were cultivated in normal environment. After exposure 8 weeks, we use Vevo 2100 machine to acquire heart function measurements. Then we collected blood sample and killed mice and obtain heart samples that were used for immunohistochemistry. The apoptosis myocardium were measured by immunofluorescence. Elisa method was used to detect the catecholamine expression in plasma. The changes of collagen were measured by Masson trichrome staining.ResultsCompared with the sham group, the EF in MI exposure group and the MI group decreased significantly (p<0.05), and the decrease in MI exposure group was more obvious. The results of immunofluorescence showed that the number of apoptotic cells in MI exposure group increased significantly (p<0.05) and the myocardial cells exaggerated significantly. In addition, the norepinephrine in the peripheral blood of MI exposure group was increased significantly (p<0.05), in the same time the Marsson trichrome staining results showed that the collagen content of MI exposure group's myocytes increased significantly (p<0.05).ConclusionNano‐zinc particles inhalation can aggravated ventricular remodeling and heart dysfunction and increased myocardial cell apoptosis after myocardial infarction in mice.Support or Funding InformationShenzhen Science and Technology Innovation Institution (China) Grant JCYJ20160427170536358 (Y Huo)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Distilling Research Projects into Graphical Abstracts: Interactive Training During a Summer Research Fellowship
Authors: Aleksunes Lauren M , Laskin Debra L 
Published: June 2021

Short‐term research experiences such as summer fellowship programs provide students with an opportunity to develop their research skills, explore career options, and improve written and oral communication skills. Most summer research programs for undergraduate students require a final poster or podium presentation. At Rutgers University, we developed an interactive session for undergraduates to conceptualize and draft written and graphical abstracts that would summarize the major findings of their research. These were distributed at our research symposium. During week 7 of a 10‐week summer undergraduate research fellowship, students learned about the major components of an abstract using a variety of examples. Students were also taught common pitfalls to avoid in communicating research findings. After the discussion of each of the opening sections (title, introduction, hypothesis, and methods), students were provided 5‐minutes for writing. After each portion of the abstract was composed, students volunteered to share their writings with the group, and the moderator provided constructive comments. Different examples of graphical abstracts were also presented to the students. Thirty students submitted abstracts during week 9 of the summer fellowship program which were assembled into booklets for the final research presentations. This interactive activity received the highest programmatic rating of the summer fellowship with a mean score of 4.58 (±0.59 SD) on a Likert scale of 1 to 5 with 5 representing the highest possible rating. Other weekly activities were also well‐received with mean scores ranging from 3.44 to 4.60. Taken together, an interactive session that includes didactic instruction and student responses allows undergraduate students to begin writing and designing their written and graphical abstracts as part of a summer research fellowship.Support or Funding InformationSupported by NIEHS R25ES020721, P30ES005022, ASPET, and the SOT Intern Program.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Client‐based Classroom Undergraduate Research Experiences (CUREs) Benefit Faculty
Authors: Wisinski Jaclyn A , Cooper Scott T 
Published: June 2021

Faculty are expected to establish and maintain research productivity, while demonstrating continuous innovation and improvement in teaching, especially at primarily undergraduate institutions (PUIs). These expectations can be quite daunting for early career faculty. However, a client‐based classroom undergraduate research experience (CUREs) can help faculty “clients” start research projects, provide professional development, recruit trained undergraduate research students and gain experience. At the University of Wisconsin‐La Crosse, each semester at least four different 300 and 400‐level biology and biochemistry courses, use the CURE model with fellow faculty members, often junior faculty, as clients. CURE instructors advise clients on the design and feasibility of specific projects in the multi‐week framework of the specific CURE course. With a reasonable research plan in mind, clients present the background, rationale and hypothesis as well as a basic outline of the experimental plan to students. In class sizes of 20–30, teams of 2–4 students work collaboratively on a research product (assay, mutant, clone, a set of data) and provide research documentation in the form of a complete lab notebook and final report. Clients and CURE instructors work together to guide students though each step of the experimental process, defining the molecular bases of techniques along the way. In the end, clients receive a formal lab report, research product and lab notebooks from students. In post CURE project surveys and interviews, clients reflected on the experience(s) in terms of usefulness to their research program, instructional development and career advancement. Instructor experiences were also evaluated in interviews. Based on responses by clients and CURE instructors, best practices could be established to make client‐based CURE a sustainable model for faculty development.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Caryophyllene Oxide is More Potent than Beta Caryophyllene in Attenuating the Abuse‐Related Effects of Ethanol
Authors: Oppong‐Damoah Aboagyewaah , Wood Bo Jarrett , Blough Bruce , Murnane Kevin Sean 
Published: June 2021

17 million adults in the United States had an alcohol use disorder (AUD) in 2012 and current treatments yield disappointing remission rates. In recent years, the endocannabinoid system has been shown to modulate the abuse‐related effects of ethanol. In this study, we used the loss of righting reflex (LORR) assay to assess the direct pharmacodynamic interactions between beta‐caryophyllene (BCP), its derivative caryophyllene oxide (B Car 21), and ethanol. We investigated the effects of B Car 21 in two widely accepted animal models of ethanol abuse: two bottle choice ethanol consumption and ethanol‐induced conditioned place preference (CPP). Finally, we determined whether there is any pharmacokinetic interaction between B Car 21 and ethanol using blood and brain ethanol analysis. B Car 21 augmented the ethanol‐induced LORR at a dose tenfold lower than BCP. This effect was reversed by pretreatment with a selective CB2 antagonist, AM630. B Car 21 significantly decreased ethanol intake and preference without any effect on total fluid intake in mice that consumed high amounts of ethanol. In mice that consumed low amounts of ethanol, B Car 21 had no effect on ethanol intake, preference, or total fluid intake. B Car 21 significantly attenuated the expression of an ethanol‐induced CPP. Our findings show that B Car 21 is more potent than BCP in vivo and that its attenuation of the abuse‐related effects of ethanol is likely mediated through pharmacodynamic rather than pharmacokinetic interactions. This study expands the support for the CB2 receptor as a viable target for the treatment of AUD.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Protective Role of MCPIP1 in Brain Injury Following Hypoxic‐Ischemia in Neonatal Mice
Authors: Naik Radheya , Chang Yingzi , Han Byynghee Henry 
Published: June 2021

Neuroinflammation has been implicated with neurodegenerative diseases and acute brain injuries such as stroke. Monocyte chemotactic protein‐1‐induced protein‐1 (MCPIP1) is a multifunction inflammatory modulator known to have pro‐inflammatory or anti‐inflammatory effects depending on the nature of brain injury. However, its role in brain injury after asphyxia in the developing brain has not been studied. Therefore, we explored the role of MCPIP1 in acute neurodegeneration after hypoxic‐ischemia (HI) in the neonatal mouse model. Neonatal C57BL/6 wild type mice at postnatal day 7 (P7) underwent a carotid artery ligation and exposure to hypoxia (8% oxygen) for 42 minutes. After the HI insult, we determined the time‐course and the spatial distribution of MCPIP1 expression in the brain. To determine the impact of MCPIP1 in acute brain damage, we assessed brain tissue loss 1 week post‐HI brain injury in MCPIP1‐deficient versus wild type mice. Western blot analysis was used to determine MCPIP1 protein expression in the brain. Caspase‐3 activity assays were used to determine apoptotic cell death, and immunoflorescent double‐labeling was utilized to determine the scope of neuroinflammation in different types of cells including astrocytes, microglia, and neuronal cells. Our data revealed that MCPIP1 protein is expressed in the neonatal brain and its expression appears to increase 24 hours after HI insult. Immunostaining showed that MCPIP1 expressing cells are present in both neuronal and non‐neuronal cells of the brain, and that there are increased numbers of MCPIP1‐positive cells in the ipsi‐lateral hemisphere compared to the contra‐lateral hemisphere. Furthermore, there was significant change in brain tissue loss after HI in MCPIP‐1‐deficient mice compared with wild‐type mice. Our data suggest that HI brain injury appears to induce expression of MCPIP1, supporting a possible role of MCPIP1 in neuroinflammation after HI.Support or Funding InformationThis study is funded by KCOM‐ Biomedical Graduate Program, Warner/Ferumaturo Grant, and ATSU Start‐up Fund (BHH).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Assessing the Neuroprotective Effects of Docosahexaenoic Acid in 6‐Hydroxydopamine Induced Parkinsonism in Rats
Authors: Chitre Neha M , Wood Bo , Ray Azizi , Moniri Nader H , Murnane Kevin S 
Published: June 2021

Parkinson's Disease (PD) is the second most common neurodegenerative disease throughout the United States. Dopamine (DA) Replacement Therapy is the standard treatment for the motor symptoms of PD. However, there is growing interest in studying newer therapeutic compounds. Polyunsaturated omega‐3 fatty acids have been associated with neuroprotective roles. In this study, we aimed to investigate the neuroprotective effects of Docosahexaenoic Acid (DHA) in 6‐Hydroxydopamine (6‐OH‐DA) unilaterally lesioned rats. Behavioral assays were conducted for the assessment of locomotor activity, stride length and limb asymmetry. Neurochemical analysis of DA levels and its major metabolite DOPAC in the striatum was performed using high performance liquid chromatography (HPLC‐ED). Biochemical estimation of oxidative stress markers like Glutathione and Reactive Oxygen Species (ROS) was conducted. Semiquantitative measurements of total Tyrosine Hydroxylase (TH) and Phospho‐TH (Ser 40) in striatal homogenates were assessed using Western Blot analysis. Our results demonstrate that DHA significantly improved stride length and limb asymmetry in the parkinsonian rats. No significant improvement was observed in locomotor activity. DHA significantly improved dopamine levels in the lesioned striatum along with a significant decrease in oxidative stress markers. There was a significant increase in expression of total Tyrosine Hydroxylase (TH) and Phospho‐TH (Ser 40) with DHA treatment. In conclusion, DHA protected the dopaminergic neurons and led to increased dopamine levels and improved motor function. We are currently studying the specific role and mechanism involved to establish a link between DHA mediated neuroprotection and increased levels of Tyrosine Hydroxylase. These results support targeting free fatty acid systems for the development of new therapeutics for PD.Support or Funding InformationStudies were supported by the National Institute of Neurological Disorders and Stroke, a component of the National Institutes of Health, by grant number NS095239. Moniri N – Principal Investigator; Murnane KS – Co‐InvestigatorThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Dendrobii Officinalis Flower improved learning and memory impairment by mediating antioxidant effect in Senescent Rats
Authors: Lei shanshan , Yan Mei qiu , Lv Guiyuan , Chen Suhong 
Published: June 2021

Aging is a necessary process, with the main feature of structural and functional decline, adaptability and resistance weakened, accompanied with obvious feature of memory dysfunction. At present, the aging of population has become the basic situation in China. Elderly people aged over 60 had reached 130 million in the year of 2007, accounting for 10% of the total population. It is expected that to 2020 year, the aging population will reach 2.24 to 3 million. To the year of 2050, 60 years of age will be more than 400 million. Therefore, it is important to study methods to delay senility to improve the quality of life of elderly and prevent and control the incidence of senile diseases.Dendrobii Officinalis Flower (DOF), which is belong to Dendrobium officinale, is very popular to people for the effect of anti‐aging in China, but lack of corresponding pharmacological experiments. The aim of was to evaluate whether DOF has effect on antioxidant enzymes and improving the brain function in aging rats. DOF was administrated at a dosage of 1.38, or 0.46 g · kg−1 once a day, as well as with a normal control group and senescent control group for 8 weeks. The results showed that DOF could improving the learning function of the escape latency, total distance and target quadrant time at 1.38 g · kg−1 and 0.46 g · kg−1 in Morris water maze experiment, as well as increasing level of γ‐GABA. In addition, DOF (1.38 g · kg−1) could decrease the levels of MDA, Glu and MAO‐B, improving locomotors, SOD and GSH‐P x. Histopathological study showed DOF also could significantly reduce structural lesions and neurodegeneration in the hippocampus. In conclusion, DOF could alleviate brain aging and ameliorate the bodily functions, which may be due to attenuating body's oxidative stress, improving hippocampus damage, and balance the release of neurotransmitters.Support or Funding InformationThis study was supported by the National Key Research and Development Program (No. 2017YFC1702200), the National Science Foundation of China (No. 81673638, No. 81874352, No. 81703772 and No.81803760), the China Postdoctoral Science Foundation (No. 2018M632506)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Elucidating Anti‐Inflammatory Signaling Paradigm at the 5‐HT2A Receptor
Authors: Billac Gerald , Nichols Charles 
Published: June 2021

Given the recent resurgence of clinical interest in the application of classical serotonergic psychedelics as treatment for various disease states, a comprehensive analysis of the structure‐activity relationship (SAR) is necessary to fully understand the differential expression of behavioral and physiological effects elicited by these compounds. While the field is mostly focused on action within the central nervous system, previously published data from the Nichols laboratory supports the use of serotonin (5‐hydroxytryptamine; 5‐HT) 2A receptor (5‐HT2AR) agonists as potent modulators of tumor necrosis factor alpha (TNF‐α)‐mediated inflammatory responses in the periphery. Whereas whole organism models will provide insight into the physiological response profile, the mechanism of action and structural basis mediating the anti‐inflammatory activity have yet to be elucidated on a molecular level. In this study, we are characterizing the signaling pathway activation profile of a comprehensive panel of 5HT2AR ligands comprising three chemical classes: tryptamines, ergolines, and phenethylamines. We hypothesize that a distinct signaling pathway elicited by 5‐HT2AR activation is mediating the differential anti‐inflammatory response to these ligands. With this data, the varying degree of effector pathway bias can also be determined for each ligand, which, from a pharmacological standpoint, will support better understanding of adverse and favorable therapeutic activities, as well as, to inform structure‐activity studies and drug candidate selection matrices. Initial results from examination of the canonical Gαq pathway – using a calcium mobilization measure – and recruitment of the multi‐adaptor protein β‐arrestin2 – using a luciferase reporter gene assay – exhibit no significant correlation between potency and efficacy for either pathway with in vivo measures of anti‐inflammatory activity. Ongoing studies are examining additional GPCR‐mediated signaling (Gi, Gs) via comparative analysis of cAMP accumulation. The collective analysis of a comprehensive panel of 5HT2AR ligands has never been examined in this fashion; thus, we aim to elucidate the SAR to inform drug design for novel molecules that are biased to pathways targeting a biologically therapeutic response.Support or Funding InformationEleusis PBCThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Inter‐Subunit Conformational Dynamics and Allosteric Modulation of Metabotropic Glutamate Receptors
Authors: Levitz Joshua , Gutzeit Vanessa , Thibado Jordana 
Published: June 2021

Metabotropic glutamate receptors (mGluRs) are class C G protein‐coupled receptors (GPCRs) which function in synapses throughout the central nervous system where they respond to the excitatory neurotransmitter glutamate to initiate intracellular signaling cascades. A comprehensive understanding of mGluR activation requires a mechanistic description of the effects of both extracellular ligand binding domain(LBD)‐targeting “orthosteric” and transmembrane domain (TMD)‐targeting “allosteric” compounds, both of which have therapeutic potential. Here we use a combination of high resolution, time‐resolved functional and conformational assays to dissect the mechanisms by which allosteric compounds activate and modulate mGluRs. First, using an electrophysiological assay we find that mGluR2 can be activated by both orthosteric or allosteric ligands and that allosteric activation does not require LBD closure. We then use a single molecule fluorescence‐based subunit counting assay to find that mGluR transmembrane domains efficiently dimerize with variable efficiency to a degree that is consistently higher than that observed for class A GPCRs and is not sensitive to allosteric drugs. Next, we develop an inter‐TMD FRET assay that reveals that activation‐associated inter‐TMD rearrangement occurs independently of allosteric input from the LBDs. Using this assay, we test a panel of allosteric compounds to uncover diversity in apparent affinity, efficacy and kinetics between these compounds. Strikingly, we find that negative allosteric modulators are either neutral or induce TMD rearrangement which correlates with degree of inverse agonism. Together this data is consistent with a model where multiple (>2) intersubunit reorientations are part of the activation process and motivates further work on the role of multimeric assembly and inter‐domain coupling in the activation of class C GPCRs.Support or Funding InformationThis work is supported by an NIGMS R35 (R35 GM124731) grant to JL. JKT is supported by an NSF GRFP.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
YM‐254890 is a General Inhibitor of G Proteins
Authors: Peng Qianman , Shen Jianzhong 
Published: June 2021

Small molecular chemicals that target individual subtype of G proteins including Gs, Gi and Gq has been lacking, except for pertussis toxin that has been validated as a selective peptide inhibitor of the Gi protein. Recently, a cyclic depsipeptide compound termed YM‐254890 was isolated from the culture broth of Chromobacterium sp., which was reported as a selective inhibitor for the Gq protein by blocking GDP exchange of GTP on the α subunit of Gq complex; however, functional selectivity of YM‐254890 towards various G proteins remains unclear, primarily due to its restricted availability before 2017. Here, using primary human coronary artery endothelial cells (HCAEC) as a testing model, we performed a systemic pharmacological study on the functional selectivity of YM‐254890 on multiple G protein‐mediated receptor signaling. First, we confirmed that YM‐254890, at 30 nM, abolished 100 μM UTP activated P2Y2 receptor‐mediated Ca2+ signaling, indicating its potent inhibition on the Gq protein. However, unexpectedly, pretreatment of HCAEC with 30 nM YM‐254890 also significantly suppressed (>50%) 100 μM adenosine‐induced cAMP elevation by Gs‐coupled adenosine A2 receptors; furthermore, we found that 30 nM YM‐254890 significantly reversed CXCL12 activated CXCR4‐Gi protein mediated suppression of cellular cAMP level, suggesting a blockage of Gi proteins. Western blotting assay indicated that YM‐254890, at 30 nM, abolished MAPK signaling triggered by P2Y2, CXCR4 and adenosine A2 receptors. Nonetheless, no cellular toxicity was observed for YM‐254890 up to 1 μM, and it neither affected A23187‐induced Ca2+ signaling, nor forskolin‐induced cAMP elevation and growth factor‐induced MAPK signaling. We conclude that YM‐254890 is not a selective inhibitor for the Gq protein, instead it acts as a broader spectrum inhibitor for Gq, Gs and Gi with a high potency, without affecting non‐GPCR‐mediated cellular signaling.Support or Funding InformationSupported in part by NIH grant 1R01HL125279‐01A1 (to J.S.)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.