bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring pain mechanisms, drug effects and sex dimorphism with proteomics
Authors: Svensson Camilla Ingegerd 
Published: June 2021

This presentation will give examples of how examining global peptide and protein expression profiles can aid in advancing our understanding of pain mechanisms and effects of pharmacological intervention. Furthermore, the importance of being aware of and understanding the limitations of different extraction methods for peptidomic and proteomics analysis will be highlighted. High‐mobility group box‐1 protein (HMGB1) has emerged as a danger‐associated molecular pattern molecule protein with important roles in various diseases and injury states. Spinal delivery of disulfide HMGB1, which is an endogenous toll like receptor 4 (TLR4) ligand, leads to an increase of factors associated with microglia reactivity in both male and female mice. Interestingly, intrathecal administration of minocycline, frequently used as a microglia inhibitor, attenuated disulfide HMGB1‐induced mechanical hypersensitivity in male but not in female mice. In order to advance our understanding of how HGMB1 induces pain as well as the basis for the sex‐dependent minocycline effect, we examined the global spinal peptide and protein expression profile using LC‐MS/MS. Using a 2×2 factorial design we found that male and females subjected to disulfide HMGB1 show a differential regulation of spinal protein expression. In addition, upon treatment with minocycline there was a striking difference in expression and a statistically significant interaction between gender and the injection effect of minocycline. Thus, the importance of mapping sex‐associated differences in pain mechanisms will be discussed, as well as opportunities and challenges using global protein expression analysis as a basis for such work.Support or Funding InformationSwedish Research Council (2013–8373), Knut and Alice Wallenberg Foundation, William K. Bowes Foundation, European Union Seventh Framework Programe (FP7/2007–2013) under grant agreement No. 602919 (GLORIA) and European Union Horizon 2020 research and innovation program under the Marie Sklodowska‐Curie grant agreement No. 642720 (BonePain).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Metformin Activates Neural Stem and Progenitor Cells in the Spinal Cord and Improves Functional Outcomes Following Injury
Authors: Gilbert Emily A.B. , Morshead Cindi M 
Published: June 2021

Across mammals, spinal cord injuries (SCI) result in devastating functional deficits with minimal treatment options. Neural stem and progenitor cells (NSPCs) exist within the spinal cord and are located in the periventricular region lining the central canal. Although normally relatively quiescent and non‐neurogenic, these NSPCs are activated in response to injury, however their response is not sufficient to support functional recovery. Enhancing the response of resident NSPCs is an innovative approach to improve structural and functional outcomes following SCI. The FDA‐approved drug metformin (MET) has demonstrated efficacy in promoting neural repair in the injured brain where it expands the size of the NSPC pool and promotes both oligogenesis and neurogenesis from NSPCs. Here, we seek to determine whether MET can influence NSPCs within the spinal cord prior to and following SCI. Using the in vitro colony‐forming assay (neurosphere assay) we examined the size of the neural stem cell (NSC) pool in the spinal cord following 7 days of in vivo MET treatment. Females, but not males, demonstrated a three‐fold increase in the size of the NSC pool in response to MET treatment. Conversely, the differentiation profile of male and female‐derived NSPCs was not sex dependent in the presence of MET. Our results show that MET exposure led to an increase in oligogenesis across both males and females, with no change in neurogenesis. Next, we evaluated whether MET administration would improve functional outcomes following SCI using a dorsal column lesion in the thoracic spinal cord. MET was delivered to animals immediately post‐SCI and treatment resulted in a significantly reduced impairment at 7 days post‐injury (DPI) on a skilled walking task, compared to vehicle‐treated SCI mice. Strikingly, MET‐treated mice recovered to baseline by 14 DPI. Our data reveals that MET has differential effects on spinal cord NSPCs across males and females and that MET administration reduces the severity of SCI and results in improves functional outcomes post‐injury. Taken together, our results support MET as a viable therapeutic strategy for enhancing neural repair and improving recovery following SCI.Support or Funding InformationAmerican Association of AnatomistsOntario Institute for Regeneration MedicineKrembil FoundationThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Anatomy Nights—A Public Engagement Format Bringing Experts to the Public
Authors: Sanders Kat , Philp Janet 
Published: June 2021

Anatomy Nights is a public engagement event created, organised, and hosted by anatomists that highlight the amazing architecture of our bodies. The public's appetite for anatomy is growing. However, the involvement of experienced and expert anatomists in many popular events is limited and it is time we got involved. In 2018, we held two sold‐out Anatomy Nights across five locations around the UK, reaching an audience of over 400 people. Each event focused on a specific organ: the heart on Valentine's Day, and the brain in the week around Halloween.Anatomy Nights brings the fundamental practice of dissection into the public sphere and gives audiences a chance to hear from anatomy experts in casual spaces such as bars and pubs. There is a general structure followed at each location. The event starts with a talk on the organ of focus, covering the basics of where is it, what does it look like, and what does it do? This is followed by a dissection of the organ (acquired from a butcher or similar source), and after a short break it all wraps up with a Q&A session.The aim of the event is to increase the publics' knowledge about their own bodies. As the audience come in, we ask them to complete a pre‐talk questionnaire that establishes the baseline knowledge. The data from these questionnaires give us an insight into the standard level of anatomy that the public knows and the common misconceptions that they hold (e.g. location of the heart often thought to be left and lower than actuality). After the dissection, the questionnaire is repeated. Everything in the questionnaire is covered in the talk, so we can see from the responses what particular anatomical knowledge the audience now know, and what topics people still struggle with.The organisation of Anatomy Nights is achieved at two levels. A core team arrange dates and themes, promotional material, presentation material, ticketing and supports the local teams. Each location then organises what they need on the ground (venue, the organ for dissection, AV equipment, volunteers to assist, etc.)Past events have been hosted by both seasoned and novice science communicators. A key benefit of the shared platform is that we are building a public engagement community in anatomy with a common goal: to ensure that the public has greater access to anatomy knowledge from reliable and expert sources; the anatomists themselves. We aim to encourage more anatomists to step out of the lab and host their own Anatomy Nights events around the globe, with the support of a growing Anatomy Nights community that brings the anatomist directly to the public.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Learning Styles and Evidence‐Based Approaches to Education
Authors: Newton Phil 
Published: June 2021

The basic idea behind the use of ‘Learning Styles' classifications is to diagnose learners into one or more of a handful of ‘styles' (e.g. Visual, Auditory, Converger) and then teach students according to their supposed style. This idea has been repeatedly tested and does not improve learning, according to current experimental evidence. Continued use of a teaching method that is not evidence‐based is potentially associated with negative effects on learning, particularly where learners are compartmentalized into a small number of ‘styles'. Despite this lack of evidence, survey and literature review research I will present here demonstrates that belief in the use of Learning Styles appears to be widespread amongst teaching staff in Higher Education (58%). This may be in part due to the continued publication of research papers that are based on the premise that matching teaching to Learning Styles is an effective approach. However the percentage of respondents who reported actually using Learning Styles in the last year (33%) was lower. Far more reported using a number of techniques that are demonstrably evidence‐based. As a group, participants agreed with all the posited weaknesses and negative consequences of Learning Styles theory. However, a substantial number of participants (32%) stated that they planned to continue using Learning Styles despite being presented with the lack of an evidence base to support them, suggesting that a ‘debunking’ approach to belief in Learning Styles may not be an effective way to promote evidence‐based approaches education. Qualitative comments revealed a number of potential reasons why belief in Learning Styles persists.Support or Funding InformationN/AThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
This is your brain on education – how an understanding of the human brain can give us insights into best approaches to teaching and learning
Authors: Krebs Claudia 
Published: June 2021

The human brain defines who we are, how we perceive and process the world around us, how we interact with each other and our environment. The human brain has the unique ability for interpretation, imagination, and creativity. The implications of these functions are profound for how we learn and an understanding of how the brain processes and responds to information can lead to new approaches in education.The cortex plays a huge role in all of our cognitive processes – extensive work has been done to map the cortex and areas that are important for learning. From a more generalist perspective, while the temporal cortex is important for the recognition of people, objects, and patterns, the prefrontal cortex is the site of our reasoning and our imagination. The question for educators is how do we motivate and engage students to learn? How do we capture their attention? Subcortical structures such as the limbic system are important for affective‐motivational processing and memory formation, the basal ganglia integrate the sum of our cortical activity into one cortical – cognitive and behavioral – output. Finally, the cerebellum helps automate processes in our brains. Together, these are some of the neuroanatomical substrates and networks that need to be engaged for an effective approach to education. Learning requires a multi‐faceted approach and each aspect of learning will engage neural networks that will process, interpret, remember and forget the information or situation we are presented with. Mindful pedagogical planning can engage the brain on both a cognitive‐procedural level as well as an affective‐motivational level, which leads to better learning outcomes: we remember what we care about. The human brain is not a static organ and the neuroplasticity that occurs during learning can give us insights into what constitutes a truly transformative learning experience.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
De novo Lipogenesis in Adipocytes Results in the Production of Structurally Novel Signaling Lipids with Beneficial Metabolic and Anti‐inflammatory Effects
Authors: Kahn Barbara B. 
Published: June 2021

Increased de novo lipogenesis in adipose tissue is associated with enhanced insulin sensitivity in humans and rodents. Mice overexpressing the Glut4 glucose transporter in adipose tissue have elevated adipose tissue lipogenesis and increased glucose tolerance in spite of obesity and elevated circulating fatty acids. Untargeted lipidomic analysis of adipose tissue from these mice revealed marked elevation of a structurally novel class of lipids, branched Fatty Acid esters of Hydroxy Fatty Acids (FAHFAs). More than 25 FAHFA family members, which are distinguished by different acyl chain composition, have been identified in mammalian tissues and plants. Levels of some family members such as Palmitic Acid esters of Hydroxy Stearic Acids (PAHSAs) are highly regulated in altered nutritional and metabolic states. PAHSA levels are reduced in serum and subcutaneous adipose tissue of insulin‐resistant humans and serum PAHSA levels correlate very strongly with insulin sensitivity in humans. Chronic PAHSA treatment improves glucose tolerance and insulin sensitivity in insulin‐resistant mice. PAHSAs also have anti‐inflammatory effects in states such as obesity, colitis and auto‐immune Type 1 diabetes in mice. Many effects of PAHSA are mediated through G‐protein coupled receptors. Thus, PAHSAs exert multiple beneficial metabolic and anti‐inflammatory effects in diabetes and immune‐mediated diseases. The pathways that regulate these lipids provide new opportunities for disease prevention and treatment.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Modification of mRNA by snoRNA‐guided 2′‐O‐methylation
Authors: Holley Christopher , Elliot Brittany , Ho Hsiang‐Ting 
Published: June 2021

Post‐transcriptional modifications of messenger RNA (mRNA) are emerging as an important layer of regulatory control over gene expression. Base modifications, especially N6‐methyladenosine (m6A), influence mRNA splicing, stability, and translation by altering base‐pair interactions and recruiting or inhibiting RNA‐binding proteins. While there is evidence that internal ribose modification by 2′‐O‐methylation (Nm) also occurs on mRNA, questions have been raised regarding its detection, and no biological role has been validated for this modification in cells or tissues. Here we show that internal 2′‐O‐methylation of mRNA serves as a new mechanism of genetic regulatory control, with the ability to influence mRNA abundance and protein levels, both in vitro and in vivo. Using genetic models, we show that this requires: (1) small nucleolar RNAs (snoRNAs), and (2) the snoRNA‐guided 2′‐O‐methylase (fibrillarin, Fbl). Since there are hundreds of box C/D snoRNAs (SNORDs) that can guide Nm modifications, snoRNA‐guided modification of mRNA could be a widespread mechanism of post‐transcriptional gene regulation. Overall, these findings show that SNORDs guide 2′‐O‐methylation of mRNA, and that Nm can provide a significant post‐transcriptional regulatory mechanism to regulate physiologic gene expression in vivo.Support or Funding InformationThe following funding sources supported this work: NIH K08HL114889, R03HL135475, and Duke Heart Center Junior Faculty Development Award to C.L.H., AHA 14POST20380015 and NIH T32HL7101‐42 to B.A.E., and AHA 16POST27540007 to H.H.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Single Cell Genomics: When Stochasticity Meets Precision
Authors: Xie Sunney , Chen Chongyi , Xing Dong , Tan Longzhi , Chapman Alec , Lee David 
Published: June 2021

DNA exists as single molecules in individual cells. Genomic variations such as copy‐number variations (CNVs) and single nucleotide variations (SNVs) in a single cell occur in a stochastic way, necessitating single‐cell and single‐molecule measurements to be identified. However, existing single‐cell whole genome amplification (WGA) methods are limited by low accuracy of CNV and SNV detection. We have developed transposase‐based methods for single‐cell WGA, which have superseded previous methods.With the improved genome coverage of our new WGA method, we have also developed a high‐resolution single‐cell chromatin conformation capture method, which allows for the first 3D genome map of a human diploid cell.Gene expression is also stochastic due to the fact that the DNA exists as single‐molecules in individual cells. The correlations among different mRNAs in a single‐cell are masked within the stochastic gene expression noise. We have developed a method for single‐cell transcriptome with improved detection efficiency and accuracy, revealing intrinsic correlations among all detected mRNAs in a single‐cell. For a particular human cell type, we uncovered ~120 transcriptionally correlated modules (TCMs) from the gene expression data of ~700 individual cells under a steady state condition. We found that the TCMs are cell type dependent.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Penta‐O‐Galloyl‐β‐D‐Glucose (PGG) Anti‐Proliferative and Pro‐Apoptotic Effect through Up‐Regulation of Tumor Necrosis Factor and its Receptors in Triple Negative Breast Cancer Cells
Authors: Mendonca Patricia , Alghamdy Sumaiah , Messeha Samia S , Soliman Karam F. 
Published: June 2021

1,2,3,4,6‐Penta‐O‐Galloyl‐β‐D‐Glucose (PGG) is a naturally occurring polyphenolic compound found in many medicinal plants such as Rhus chinensis Mill and Paeonia suffruticosa. PGG potential in chemoprevention has been reported in many cancer studies including lung, prostate, breast, liver, and sarcoma. In mechanistic studies, PGG modulated apoptosis, angiogenesis, metastasis, and signaling pathways. In the present study, we investigated PGG anti‐proliferative and pro‐apoptotic effects in MDA‐MB‐231 (Caucasian) and MDA‐MB‐468 (African American) triple‐negative breast cancer (TNBC) cells; recognized as the most aggressive type of breast cancer with poor prognosis. The results showed that PGG inhibited cell viability of both cell lines in a dose‐dependent manner. Notably, PGG was 5‐fold more potent in African American cells (IC50 35.7 μM) compared to MDA‐MB‐231(IC50 176.1 μM). PGG anti‐proliferative effect was similar to Taxol in concentrations of 50 and 25 μM in MDA‐MB‐231 and MDA‐MB‐468, respectively, demonstrating more effectiveness in African American cells compared to Caucasians. Results obtained from Annexin V/PI flow cytometry showed that PGG treatment induced 42.3% of apoptosis in Caucasian, and 62% in African American breast cancer cells in the concentration of 100 μM. Subsequently, the expression of several genes associated with apoptosis regulation was detected by RT‐PCR assay to explore underlying apoptosis mechanisms. PGG increased mRNA expression of apoptosis genes in 5‐fold or more in both cell lines, inducing the expression of 12 genes in MDA‐MB‐231, versus 5 genes in MDA‐MB‐468 cells. Remarkably, the highest increase was seen in Tumor Necrosis Factor (TNF) expression which presented a 154.6‐fold increase in African American cells, compared to 14.6‐fold in MDA‐MB‐231. TNF Receptor Superfamily Member 10a (TNFRSF10A) expression was also increased in both cell lines; however, TNF Receptor Superfamily Member 9 (TNFRSF9) expression was induced exclusively in MDA‐MB‐231 cells. TNF‐induced apoptosis is known to be mediated through activation of type I receptors, the death domain of which recruits many different signaling proteins, which together are considered part of an apoptotic cascade. Therefore the results suggest that PGG could be a potential inducer of apoptosis in TNBC cells in Caucasian and African American women, by inducing expression of TNF and its receptors and thus offering a promising approach for cancer therapy.Support or Funding InformationThis research was supported by grants received from NIH NIMHD G12‐MD007582 and P20 MD 0006738This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Impact of Interleukin‐1 Alpha and EGFR Expression on Recurrence and Survival Outcomes in Oral Squamous Cell Carcinoma
Authors: Gibson‐Corley Katherine N. , Rajan Anand , Ofori‐Amanfo Georgina , Eyck Patrick Ten , Espinosa‐Cotton Madelyn , Sperry Steven , Simons Andrean L. 
Published: June 2021

Interleukin‐1 alpha (IL‐1α) is a pleiotropic cytokine involved in inflammation and immune response and is upregulated in many solid tumors including head and neck squamous cell carcinomas (HNSCCs). Although IL‐1α expression is generally associated with poor prognosis, the implications of the subcellular localization of IL‐1α expression in patient outcomes are poorly understood. This study is aimed at investigating the clinical relevance of nuclear and cytoplasmic immunohistochemical IL‐1α expression in oral squamous cell carcinomas (OSCCs). Tissue microarrays (TMAs) containing 146 OSCCs were analyzed for IL‐1α and EGFR expression by immunohistochemistry. Nuclear and cytoplasmic IL‐1α and EGFR expression scores were correlated with clinicopathological parameters and patient outcomes. IL‐1α expression was observed in the nuclear and/or cytoplasm compartments in 98% of evaluable tumors and 78% of tumors expressed IL‐1α in both compartments. Tumors with combined high nuclear and moderate cytoplasmic IL‐1α expression showed a trend toward worse disease‐free and overall survival compared to tumors with other nuclear/cytoplasmic IL‐1α expression profiles. EGFR expression was observed in 62% of tumors. A combined EGFR‐negative and high nuclear IL‐1α expression profile was associated with a low risk of tumor recurrence and favorable overall survival compared to all other EGFR/IL‐1α expression profiles. IL‐1α in combination with EGFR expression may be a strong indicator of risk of recurrence in OSCC and warrants further study as a tissue biomarker for predicting patient outcomes.Support or Funding InformationThis work was supported by the Department of Pathology, and National Institutes of Health (NIH) grants R01DE024550, and CTSA UL1TR002537 administered through the Institute for Clinical and Translational Science (ICTS) at the University of Iowa.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.