bluuebunny/crossref_metadata_2025_split huggingface dataset:
CHST11 Promotes Lung Cancer Metastasis through Changing Intracellular Iron Metabolism
Authors: Chang Wei‐Min , Chiu I‐An , Jan Yi‐Hua , Hsiao Michael 
Published: June 2021

Non‐small‐cell lung cancer (NSCLC) is one of the most lethal cancers, for it often develops metastasis after therapy. Cancer metastasis usually begins from epithelial‐to‐mesenchymal transition (EMT), and metabolic disorder is a key mediator of lung cancer EMT. The linkage between metabolic disorder and NSCLC EMT is still unclear. Here, we compared gene expression signatures from both TGFb induction EMT model of NSCLC cells and the EMT score from clinical NSCLC patients' cohort. We found several chondroitin sulfate (CS) biosynthesis genes were highly correlated to NSCLC EMT status. CHST11, the key enzyme of this pathway, was selected for further functional studies. Enforced CHST11 expression promoted NSCLC cells migration, invasion and increasing M‐type markers, such as Slug, N‐cadherin and Vimentin expression and vise versa. Deplete the final product of CS biosynthesis by chondroitinase ABC or enzyme‐dead CHST11 could abolish the NSCLC EMT ability from TGFb and CHST11, respectively. Moreover, we found the CHST11 expression changing the iron metabolic status in NSCLC cells and promoting the NSCLC EMT.In the end, immunohistochemistry showed that CHST11 was a poor prognostic marker of overall survival and disease‐free survival in clinical NSCLC patients. In conclusion, our findings implicated that 1) The chondroitin sulfate biosynthesis pathways is crucial for NSCLC EMT; 2) A novel CHST11‐CP‐Fe3+ pathway is involved in NSCLC EMT. 3) CHST11 is a poor prognostic marker in NSCLC patients. These results might help us to understand the role of aberrant cancer metabolism in NSCLC EMT.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Down‐regulation of Fatty Acid Transporter‐encoding Gene SLC27A3 Modulates Immuno‐response and Correlates with Poor Prognosis in Lung Adenocarcinoma
Authors: Chiou Jean , Hsiao Michael 
Published: June 2021

Fatty acid transporter 3 (FATP3, also named as SLC27A3) plays a critical role in brain development and monocyte‐macrophage differentiation. It has been reported that SLC27A3 were upregulated in CD16+ Dendritic‐like cells and CD4+ T memory cells. However, the prognostic significance and functional consequence of SLC27A3 downregulation remains unclear in human cancers. The aim of this study is to determine the prognostic values of SLC27A3. First, we searched public gene expression database and analyzed SLC27A3 protein expression by immunohistochemical staining on cancer tissue microarray samples. We showed that reduced levels of SLC27A3 were widely detected in tumors compared to normal tissues and reflect a poor clinical outcome in non‐small cell lung cancer and glioma, especially in lung adenocarcinoma. Furthermore, we verified the functional role of immune‐regulation of SLC27A3 in NSCLC cell lines. Since SLC27A3 expressed in T memory cells, we raised the hypothesis that SLC27A3‐expressed cancer cells may establish microenvironment that fit for T cells. Therefore, T cells will recruit to kill cancer cells in the nearby. In vitro T‐cell proliferation assay showed that SLC27A3 modulated the inhibition of T‐cell proliferation exerted by lung cancer cells. In conclusion, downregulation of SLC27A3 expression is an independent prognostic factor in lung adenocarcinoma patients and may play critical roles in the inhibition of immuno‐response in lung cancer.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Three‐dimensional in situ sequencing of single cells in intact tissue
Authors: Wang Xiao , Allen William E. , Deisseroth Karl 
Published: June 2021

Conventional sequencing methods are unable to measure sequence and spatial information simultaneously, limiting our understanding of the spatial heterogeneity of molecules within cells and intact tissues. To address this issue, multiplexed in situ hybridization and a new generation of sequencing methods termed in situ sequencing have emerged, aiming to spatially resolve RNAs inside cells. Such spatial transcriptomic profiling is critical to resolving cell identity in intact issues, a key question in neuroscience today as the brain consists of a three‐dimensional (3D) tapestry of cell types whose functional diversity arises from the spatial heterogeneity of gene expression. We developed a 3D intact‐tissue RNA sequencing technique in complex organs, termed STARmap, enabling targeted single‐cell gene expression mapping via in situ sequencing within mouse cortex. This new analytical approach has great promises for addressing a series of fundamental questions in neuroscience (e.g. spatial organization of cell types, molecular markers of functional circuits, activity‐triggered gene expression) that are hard to be studied otherwise.Support or Funding InformationX.W. is supported by a Life Science Research Foundation fellowship and the Gordon and Betty Moore Foundation. W.E.A. is supported by a Fannie and John Hertz Foundation Fellowship and an NSF Graduate Research Fellowship. K.D. is supported by NIMH (R01MH099647), NIDA (P50DA042012), the DARPA NeuroFAST program W911NF‐14‐2‐0013, the NSF NeuroNex program, the Gatsby Foundation, the AE Foundation, the NOMIS Foundation, the Fresenius Foundation, the Wiegers Family Fund, the James Grosfeld Foundation, the Sam and Betsy Reeves Foundation, and the HL Snyder Foundation.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
When Students Choose E‐learning Resources—the Importance of Ease and Convenience
Authors: Hortsch Michael , Rodenbarger Lauren 
Published: June 2021

Electronic learning resources are popular with today's students. How students choose their favorite e‐learning tools has not been investigated in detail and therefore is not well understood. The popular SecondLook™ (SL) Histology e‐learning self‐review tool was offered in three different formats to students participating in two different histology courses at the University of Michigan (CDB450/550 and DENT510). The SL formats included downloadable PowerPoint files, an interactive online website, and a mobile smartphone and computer tablet application (app). Identical in content, each format had specific advantages and disadvantages with respect to the types of compatible devices, user features, and access limitations. Upon the conclusion of their courses, students were surveyed about their format choices and reasons for their selection, as well as usage patterns. Only 3 out of 213 participating students (91.4% participation rate) reported not having used the SL resource. Many students (46% CDB450/550, 64% DENT510) tried only one resource format, with PowerPoint being the most popular final choice (56% CBD450/550, 64% DENT510). Although the interactive website and mobile app offered several user‐friendly features not available within the PowerPoint files, they each only garnered approximately 20% final popularity in both courses. “Convenience,” “larger screen,” and “easy to use” were given most often as reasons for students' PowerPoint software format choice. The flexibility of time and place to use the resource and availability of features were also named as factors in the format selection. The access to a mobile learning tool enticed some students to use this resource in distractive environments. It also encouraged some students to forgo other learning resources, specifically textbooks, and the course website. These results suggest that today's students are in fact less motivated to actively seek out novel, high‐tech learning resources than commonly believed and instead often select easy to use and convenient review tools with which they are familiar. The study received an exempt status from the University of Michigan IRB.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The Human Evolution Teaching Materials Project
Authors: Selba Molly Chisholm 
Published: June 2021

The Human Evolution Teaching Materials Project (HETMP) was created to facilitate the inclusion of human evolution into existing middle school and high school curricula. HETMP utilizes open‐access 3D surface files of hominin crania, along with a variety of teaching materials, to reinforce a student's understanding of evolutionary processes through the analysis of hominin cranial morphology. It has been piloted in five middle school and high school classrooms during the period 2017–2018. Through a free and easy‐to‐use website, teachers have access to all of these materials as well as constant support in order to help facilitate the implementation of these materials into existing course content. The available teaching modules reference a variety of open source 3D models including: Pan troglodytes, Australopithecus africanus, A. afarensis, A. sediba, Paranthropus aethiopicus, P. boisei, Homo naledi, H. erectus, H. rudolfensis, H. habilis, H. heidelbergensis, H. sapiens, and H. neanderthalensis. These models can be printed by the school or by using a local 3D printer, or can be borrowed from a previously established set of crania. This program not only highlights the importance of keeping academic research open‐source, but also has a direct impact on evolution awareness in hundreds of middle and high school students. Teachers at the pilot schools noted increased student engagement and students have enjoyed learning about human evolution in a way that was previously not made available to them. Undoubtedly, HETMP has the potential to impact thousands of pre‐college students by demonstrating the tangible evidence of evolution and allowing middle school and high school students to learn about cranial morphology through hands‐on experiential learning.Support or Funding InformationThis project is supported by the Society for the Study of Evolution.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Anatomical Exploration of the Tympanic Cavity Using Virtual and Printed 3D Models of the Human Petrous Bone
Authors: Zdilla Matthew J , Skrzat Janusz , Walecki Piotr , Tarasiuk Jacek 
Published: June 2021

The tympanic cavity is, from a gross anatomical perspective, both small and complex. Scaling the anatomy of the tympanic cavity to a larger size, while maintaining accuracy with regard to detail, could improve the understanding of the anatomy. Therefore, the purpose of this study was to create an accurate 3D computer model of the tympanic cavity and materialize it, in a larger scale, via 3D printing. The 3D virtual model of the tympanic cavity was created from serial micro‐CT scans of a normal temporal bone and converted into stereolithography files dedicated for 3D printing. Micro‐CT scanning of the petrous bone was performed with aid of the Nanotom 180N device with a slice thickness of 15 μm. To obtain the 3D virtual model of the tympanic cavity, automatic image segmentation was performed with CT‐An software, which generated the mesh of triangles that approximated the geometry of the tympanic cavity. To create a polymer mass from the digital model, the Da Vinci 1.0 printer (nozzle diameter = 0.4 mm), which utilized prototyping technology based on fused filament fabrication, was employed in order to build the model with the acrylonitrile butadiene styrene at the layer height = 0.3 mm. The study demonstrated the possibility of building accurate models of the tympanic cavity that expose anatomical details including the oval window, round window, promontory, pyramidal evidence, subiculum, ponticulus, and sinus tympani— structures with dimensions in the range of only a few millimeters. Both 3D virtual and large‐scale printed models may improve the understanding of the complex anatomy of the tympanic cavity and spatial relationships between the ear components. Enlarged 3D virtual and printed models of the tympanic cavity facilitate demonstration and observation of the tympanic cavity anatomy in comparative studies.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Methocinnamox (MCAM) is an Effective Long‐Term Antagonist of Peripheral Mu, but not Kappa or Delta Opioid Receptors In Vivo
Authors: Jennings Elaine M , Disney Alex , Husbands Stephen , Winger Gail , Berg Kelly A. , Clarke William P. , Woods James H. 
Published: June 2021

The United States is currently in the midst of an opioid abuse epidemic; deaths from synthetic opioids like fentanyl and its derivatives are increasing. Currently naloxone (Narcan), a competitive mu opioid receptor antagonist is the only pharmacological treatment for opioid overdose; reversing both respiratory depression and profound sedation. However, naloxone has a relatively short duration of action and thus its effects are limited. A long lasting mu opioid receptor antagonist called MCAM has been shown to attenuate the antinociceptive effects of morphine in mice for more than 48 hours (Broadbear et al., J Pharmacol Exp Ther, 294:933–940, 2000) and due to this long duration of action, may make a better treatment for opioid overdose and perhaps for opioid abuse. Because MCAM reduces mu receptor function for a longer period relative to kappa or delta opioid receptors, we have begun to examine if pain relief from either kappa or delta receptor agonists will be active while mu receptors remain occupied by MCAM. Using the Hargreaves method for thermal heat nociception, we determined the effect of intraplantar (i.pl.) pretreatment of MCAM or vehicle on peripherally mediated reduction in PGE2‐evoked thermal allodynia by DAMGO (mu agonist), U50488 (kappa agonist) or DPDPE (delta agonist). Injection of DAMGO (20μg/50 μl i.pl.), U50488 (0.1μg/50μl i.pl.) or DPDPE (20μg/50 μl i.pl.) produced a significant reduction in PGE2‐evoked thermal allodynia. Pretreatment with MCAM 15 min prior to PGE2 injection at 10nM (0.25μg/50μl i.pl), 50nM (1.25μg/50μl i.pl) or 20nM (0.5μg/50μl i.pl), had no effect on PGE2‐induced thermal hypersensitivity; however, it significantly inhibited the antinociceptive response to DAMGO, U50488 and DPDPE. The DAMGO‐mediated antinociception remained blocked 24 and 48h after a single administration of MCAM. By contrast, when tested 24h after administration, MCAM had no effect on U50488‐ or DPDPE‐mediated antinociceptive responses. Thus, MCAM displayed long‐term antagonism at mu opioid receptors but only a short antagonist effect at either kappa or delta opioid receptors. These data suggest that MCAM's long duration of antagonist action is selective for mu opioid receptors and that peripherally restricted delta and kappa receptor agonists may be a viable option for pain relief.Support or Funding InformationThe Addiction Research, Treatment & Training (ARTT) Center of Excellence at UT Health San Antonio.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effects of Brominated Flame Retardants on Cytokine Production by Mast Cells
Authors: King Ethan D , Mahoney Jonathan , Krajewski Dylan , Smith Warren , Mathias Clinton , Bose Diptiman D 
Published: June 2021

Polybrominated diphenyl ethers (PBDEs), extensively used as flame‐retardants, have been shown to cause neurotoxicity, immunotoxicity and endocrine disruption; however, the exact mechanisms are largely unknown. In this study, we propose to investigate PBDE‐induced immunotoxicity in mast cells. We examined the effects of two of the most commonly occurring brominated diphenyl ether (BDE) congeners, BDE‐47 and ‐99, and a metabolite of BDE‐47, 6‐OH‐BDE‐47 on MC/9 mast cells. MC/9 cells treated with BDE‐47, ‐99 and 6‐OH‐BDE‐47 (0.25, 0.5, 5, 20 and 40μM, 24h) were stimulated with IgE/antigen (1μg/ml), and levels of IL‐6 were measured by ELISA. Our results indicate that PBDEs inhibit the IgE‐mediated cytokine release in MC/9 cells in a concentration‐dependent manner. Interestingly, exposure to BDE‐47 and 6‐OH‐BDE47 decreased IL‐6 release in a concentration‐dependent manner; however, BDE‐99 decreased IL‐6 release only at concentrations above 20 μM. These results demonstrate that tetra‐brominated BDE‐47 and its 6‐OH metabolite can suppress cytokine release with increasing concentrations, while penta brominated BDE‐99 congener inhibits IL‐6 release only at higher concentrations. Mast cell degranulation measured by β‐hexoaminidase also showed that BDE congeners decreased degranulation in a concentration‐dependent manner in IgE stimulated mast cells. In order to test effects on cell viability, we exposed the MC/9 cells to increasing concentrations of the BDE congeners and measured cytotoxicity at 24 and 48h by MTS assay. We found that tetra‐brominated BDE‐47 exhibited more potent cytotoxicity (EC50 μM =42.38 at 24h and 32.33 at 48h) in comparison to the penta‐brominated BDE‐99 (EC50 μM =48.41 and 35.04 at 48h) in the MC/9 cells. However, the 6‐OH metabolite of BDE‐47 was more cytotoxic in comparison to its parent compound BDE‐47 as well as penta‐brominated BDE‐99 (EC50 μM =25.82 at 24h and 20.16 at 48h). Our results suggest that PBDE congeners can modulate cytokine release in mast cells and the extent of inhibition is dependent on the bromination of PBDEs. These results address the need to better understand the molecular and cellular mechanisms by which PBDE exposure can mediate immunotoxicity.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The Effects of 16‐hour Nighttime Fasting on Markers of Oxidative Stress
Authors: Dirks‐Naylor Amie J , Wilson Jennifer A. , Waghel Rashi , Bush Mark , Cook Corbin 
Published: June 2021

Caloric restriction and intermittent fasting have shown to confer a plethora of health benefits. However, traditional regimens of caloric restriction (restricting caloric intake by 30–40% every day) and intermittent fasting (fasting every other day), have proven difficult to comply. Prolonged nighttime fasting is a type of intermittent fasting which may be an easier regimen to maintain, but has been scarcely studied. Thus, the aim of this study was to determine the effects of this regimen on biomarkers of oxidative stress. Eleven healthy men ranging in age from 21–39 years fasted for 16‐hrs (~6pm–10am) each night for 4‐weeks. Subjects were instructed to eat their normal diet outside of the suggested fasting hours. Pre‐ and post‐fasting blood samples were collected. 24‐hr food and drink intake was self‐recorded periodically before and during the fasting period using the National Cancer Institute Automated Self‐Administered 24‐hour Recall (ASA24) website. Total antioxidant capacity, DNA oxidation, thiobarbituric acid reactive substances (TBARS), and glutathione reductase (GR) activity were measured in pre‐ and post‐plasma samples. Prolonged nighttime fasting increased plasma total antioxidant capacity (p=0.001), but did not affect DNA oxidation, lipid peroxidation, or GR activity. There was no difference in the 24‐hr recall caloric intake before and after starting the fasting regimen. The fasting regimen also did not affect the percent intake of proteins, carbohydrates, fats, sugar, or fiber. Thus, the results suggest that prolonged nighttime fasting, without altering daily caloric or dietary intake, may improve antioxidant capacity.Support or Funding InformationNoneThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Characterization of GPCR6A and CaSR in Atlantic salmon (Salmo salar)
Authors: Gomes Ana Silva , Lai Floriana , Jordal Ann‐Elise O. , Rønnestad Ivar 
Published: June 2021

The G protein‐coupled receptor family C, group 6, member A (GPCR6A) and the calcium‐sensing receptor (CaSR) belong to the GPCRs family C and play a crucial role in sensing amino acids in the mammalian gastrointestinal (GI)‐tract. These receptors, located in the enteroendocrine cells facing the GI‐tract lumen, are activated by dietary amino acids, which stimulate the release of gut hormones leading to the regulation of diverse physiological functions, including digestion, absorption, allocation of substrates for growth, feed intake, etc. While it is established that these receptors play a key role in amino acid sensing in mammals, there is little information in teleosts, including Atlantic salmon (Salmo salar L.).The Atlantic salmon is a key commercial species in global aquaculture and provides an excellent model to study the fate of duplicated genes due to the salmonid‐specific 4th round of whole genome duplication. In the Atlantic salmon genome database we have identified at least three gpcr6a genes, named here gpcr6a‐like 1, ‐like 2 and –like 3. While GPCR6A‐like 1 and ‐like 2 share 93% of similarity at the amino acid level, both only share 46% of similarity with GPCR6A‐like 3. The Atlantic salmon gpcr6a exon‐intron diverges significantly from the mammalian homologue gene, however the 2D topology is well‐conserved. Regarding the Atlantic salmon CaSR, one casr gene in the chromosome (chr) ssa11 was identified and it shared a high similarity (78 %) with the human homologue. In addition, several other casr genes were found in Atlantic salmon, located in unplaced scaffolds and in the chr ssa9 and chr ssa20, which suggests that tandem duplication of casr have occurred in these chromosomes.Further, we have started to investigate the spatial mRNA expression profile for all the salmon gpcr6a transcripts and the casr transcript in chr ssa11 in several tissues, including different regions of the GI‐tract. Preliminary results indicate that these receptors are present in the oropharyngeal area, and, even though in lower expression levels, present along the different regions of the GI‐tract. Our data collected this far support the hypothesis of a conserved system for amino acid sensing in the GI‐tract across the vertebrate lineage.Support or Funding InformationFunded by Regional Research Fund West (RFFV 247978 SalmoFeedPlus), Cargill and Research Council of Norway (NFR 267626 LeuSENSE; 262096 GUTASTE).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.