bluuebunny/crossref_metadata_2025_split huggingface dataset:
New Late Jurassic Dinosaur (Ornithischia) from China Sheds Light on the Early Evolution of the Ornithopod Skeleton and Phylogeny of Ornithopoda
Authors: Spencer Marc R. , Forster Catherine A. , Poole Karen E. , Clark James M. , Xu Xing 
Published: April 2020

Numerous partial to complete individuals of a new neornithischian dinosaur have been collected from the early Late Jurassic (Oxfordian) Shishugou Formation in northwestern China. The new taxon includes an ossified clavicle and, uniquely, a patellar sesamoid and trilobate maxillary and dentary teeth. Coeval taxa from the Shaximiao Formation in Sichuan, China (Hexinlusaurus, Agilisaurus, Yandusaurus), regarded in many recent analyses as falling outside of Cerapoda (Marginocephalia + Ornithopoda), lack many characters distributed among ornithopods that are present in the new Shishugou taxon, including a large hooked coracoid process, a small quadratojugal foramen, narrow and elongate frontals, well‐developed epipophyseal ridges on the postzygapophyses of anterior cervical vertebrae, and a well‐defined and elongate femoral neck with a deep femoral capital sulcus. However, the new Shishugou taxon also retains some plesiomorphic character states relative to most ornithopods such as having five sacral vertebrae, and a short, narrow lesser trochanter on the femur. Recent analyses of neornithischian dinosaurs are not in agreement over the taxonomic composition of Ornithopoda or Cerapoda, or the distribution of characters along the neornithischian branch. Putative synapomorphies of Ornithopoda vary from study to study, as does the taxonomic composition of the clade. In some studies, many erstwhile “ornithopods” such as Thescelosaurus and Orodromeus have been pulled out of Cerapoda as basal neornithischians, while other studies recover a more inclusive monophyletic Ornithopoda. The current consensus of basal neornithischian and cerapodan phylogeny is poorly resolved. New taxa such as the Shishugou taxon that exhibit some, but not all, characters used in many studies to define Ornithopoda may help unclutter some of the resolution at the base of the cerapodan tree. The morphology present in the new taxon gives polarity to a suite of characters for basal neornithischian dinosaurs that may help provide a clearer diagnosis for Ornithopoda.Support or Funding InformationNational Science Foundation (NSF EAR 0922187, 1636753, NSF DDIG 1405834), National Geographic Society, The George Washington University, National Science Foundation of China (41120124002, 41688103)
Association between Frequency of Breakfast Consumption and Regional Body Fat Distribution
Authors: Pfeifer Michaela , Danyluk Alexandria , Smith Kevin L. , Sompalli Sreeja , Singh Prachi , Covassin Naima 
Published: April 2020

BackgroundDietary habits are critical determinants of health and especially of cardiometabolic risk status. Previous studies have examined the relationship between breakfast consumption and indices of obesity, with conflicting findings. Such discrepancy may be owed to the use of surrogate measures of adiposity such as body mass index. Furthermore, it is unknown whether frequency of breakfast consumption is associated with different patterns of regional body fat distribution.ObjectiveIn this study, we aimed at investigating the association between frequency of breakfast consumption and body fat distribution.MethodsWe compiled data from 184 individuals (64% males, mean age 35.8±12.6 years, ranging from 18 to 63 years old) who participated in research studies performed in the Mayo Clinic Cardiovascular/Sleep Laboratory from 2005 to 2019 and underwent whole body dual‐energy X‐ray absorptiometry (DXA) for body composition. Breakfast eating habits were assessed by questionnaire and frequency of consumption was determined as number of times per week (range 0 to 7). Responses were recoded as low frequency (0 to 2 times/week), middle frequency (3 to 4 times/week), and high frequency (5 to 7 times/week). Measures of height and weight were collected to compute body mass index (BMI, kg/m2). Total body fat percentage, fat mass, and lean mass were obtained from DXA. Regions of interest were manually adjusted with the DXA software to quantify abdominal fat and lower body fat. Abdominal fat/total body fat and lower body fat/total body fat ratios were calculated.ResultsLow frequency of breakfast consumption was reported by 14% of the subjects (n=26), while 18% (n=34) reported middle‐frequency of consumption. The proportion of men/women (p=0.1) and BMI values (p=0.78) were similar across breakfast eating categories. Compared to those who had breakfast with high‐frequency, those who ate it less frequently were younger (p=0.038). In age, sex, and BMI‐adjusted analysis, low‐frequency of breakfast consumption was significantly associated with greater abdominal fat mass (standardized beta=0.11, 95% CI 0.09‐ 1.29, p=0.024) and higher abdominal fat/total body fat ratio (standardized beta=0.16, 95% CI 0.003–0.024, p=0.013). Total body fat percentage (p=0.26), fat mass (p=0.26), and lean mass (p=0.22) were not associated with frequency of breakfast consumption. Similarly, no relations were seen with lower body fat (p=0.85) or lower body fat/total body fat ratio (p=0.51).ConclusionOur study showed that infrequent breakfast consumption is selectively associated with greater abdominal fat mass. As accumulation of fat in the abdominal depot is a more robust predictor of adverse outcomes than total adiposity, these findings suggest that abdominal fat may mediate the increased cardiometabolic risk previously observed in conjunction with infrequent breakfast consumption.
Lanthionine Synthetase C‐like Protein 2: A potential therapeutic target for treating neuropathic pain
Authors: Christy David , Maixner Dylan W. , Weng Han-Rong 
Published: April 2020

Glial activation and over‐production of pro‐inflammatory cytokines and chemokines in the spinal cord are critical mechanisms underlying the genesis of neuropathic pain. While pro‐inflammatory signaling molecules have been extensively investigated, much less is known about anti‐inflammatory signaling pathways and systems. Studies in recent years have demonstrated that lanthionine synthetase C‐like 2 protein (LANCL2) is expressed in cells related to the immune function, like T cells, macrophages, endothelial and epithelial cells, and dendritic cells, suggesting its potential as a target for immunoregulation. In this study, we determined the role of LANCL2 in the genesis of neuropathic pain. Specifically, we show that LANCL2 protein is expressed in spinal dorsal horn and down‐regulated in rats with neuropathic pain. Knockdown of spinal LANCL2 induces mechanical allodynia and thermal hyperalgesia, which is concomitantly accompanied with increases in extracellular signal‐regulated kinase (ERK) activity, tumor necrosis factor alpha (TNF‐α) production, and the activation of astrocytes and microglia in the spinal dorsal horn. Activation of spinal LANCL2 by intrathecal administration of abscisic acid alleviates mechanical and thermal hypersensitivity induced by nerve injury. Pre‐emptive pharmacological activation of LANCL2 prevents the down‐regulation of LANCL2 protein expression, and significantly attenuates the development of mechanical allodynia and thermal hyperalgesia in rats induced by nerve injury. These behavioral changes were accompanied with the suppression of ERK activity and TNF‐α production, and astrocyte and microglia activation in the spinal dorsal horn of rats with nerve injury. Our study provides evidence that LANCL2 may be a potential molecular target for the development of analgesics for neuropathic pain and the management of a wide range of conditions involving neuroinflammation.Support or Funding InformationNS064289; NS107569
Protection of Nitrogen Fixation from CO by CowN in G. diazotrophicus
Authors: Chong Kiersten , Garcia Chloe , Lee Terrence , Strul Max , Bretzing Kevin , Owens Cedric 
Published: April 2020

Nitrogen fixation is the process in which atmospheric dinitrogen is reduced to ammonia. Nitrogen fixation occurs naturally in certain bacteria, such as Gluconacetobacter diazotrophicus, via the enzyme nitrogenase, a multisubunit protein with an iron protein subunit (FeP) and a molybdenum‐iron protein subunit (MoFeP). Nitrogenase is inhibited by carbon monoxide (CO). Under some soil conditions, CO levels are sufficiently high to inhibit nitrogenase and prevent nitrogen fixation. However, G. diazotrophicus expresses a protein called CowN that prevents the inhibition of nitrogenase by CO. This research attempts to understand the mechanism of how CowN prevents inhibition of nitrogenase. We expressed G. diazotrophicus CowN heterologously in E. coli and purified the protein to homogeneity. In vitro studies with FeP, MoFeP, and CowN in the presence of CO showed that CowN effectively restores nitrogenase activity for CO concentrations up to 0.1 atm. The activity of CowN exhibits Michaelis‐Menten‐like kinetics with a Km of approximately 8 μM. Our experiments further show that CowN, which exists in a monomeric and oligomeric state, is only active as a monomer. Further work will aim to elucidate how CowN binds to nitrogenase and if CowN protects nitrogenase by directly preventing CO access to the active site.Support or Funding InformationThis research was supported by the Chapman Center for Undergraduate Excellence, USDA‐NIFA (Grant no. 2015‐67012‐22895) and the National Science Foundation (Grant no. 1905399).
Choline Acetyltransferase Dysfunction Caused by Mutations Associated with a Congenital Motor Disorder
Authors: Rodgers David W. , Batra Joytica , Cai Yiying , Espinosa Paul , Whitaker Abigail , Feibes Helen , Grospitch Ashley M. 
Published: April 2020

Choline acetyltransferase (ChAT) synthesizes the neurotransmitter acetylcholine, and over 20 missense mutations that reduce enzyme activity have been found in patients with a severe neuromuscular disorder known as congenital myasthenic syndrome with episodic apnea (CMS‐EA). Our structural studies showed that the disease‐causing mutations are widely distributed over the enzyme despite generally producing similar decreases in catalytic function. We report here that two of the CMS‐EA mutations (L102P and P103A) alter the conformation of the ChAT active site, likely accounting for their effects on activity. Further, we find that the core residue packing in ChAT is poor, leaving an unusually large number of cavities. Partially filling one of the cavities near the L102P site by making a second mutation restores the native conformation of the active site as well as enzyme activity. We propose that the poor core packing in ChAT mediates the effects of CMS‐EA mutations on enzyme activity by transmitting structural changes to the active site. This work raises the possibility of using one or more cavity‐binding ligands to stabilize the enzyme to a number of the CMS‐EA causing mutations. We have identified a ligand that enhances the activity of the L102P mutant and are currently defining its binding site.Support or Funding InformationResearch reported was supported by National Institutes of Health award NS079818 and by AMF‐Telethon award 18508.
Effects of Growth Factors and FFAR Agonists on CCN1 Expression in Breast and Prostate Cancer Cells
Authors: Balijepalli Pravita , NIVISON MARY P. , Meier Kathryn E. 
Published: April 2020

CCN1/Cyr61 is a secreted extracellular matrix‐associated “matricellular” protein capable of regulating a broad range of cellular activities. Several studies have established that CCN1/Cyr61 is rapidly induced at the transcriptional level when cancer cells are incubated with growth factors that facilitate adhesion signaling, thereby enhancing cancer cell migration and survival. However, the role of CCN1 induction in the proliferative responses to growth factors has not been fully delineated. In this study, we examined the changes in expression levels of CCN1 in response to lysophosphatidic acid (LPA) and epidermal growth factor (EGF) in human prostate and breast cancer cell lines. We also studied the role of free fatty acid receptors (FFARs) in this context. FFAR agonists have been previously reported to show inhibitory effects on growth factor‐mediated proliferation and migration in human prostate and breast cancer cells. PC‐3 and MDA‐MB‐231 cells were serum‐starved for 24 hours and treated with 10uM LPA, 10nM EGF, and +/‐ 1uM TUG‐891. Following the incubation, whole‐cell lysates were collected, and subsequent immunoblotting was performed. LPA and EGF induced CCN1 protein by 4 hours. TUG‐891, an FFA4 agonist, inhibited CCN1 induction by LPA. In parallel, the cells were fixed with 4% paraformaldehyde and CCN1 was visualized using confocal immunofluorescence microscopy. The localization of CCN1 following its induction is consistent with its secretion and subsequent binding to ECM components. These results suggest that CCN1 plays roles in the sequence of downstream responses to growth factors in breast and prostate cancer cells.Support or Funding InformationSupported by the ASPET David Lehr Award and by the WSU College of Pharmacy and Pharmaceutical Sciences.
Unusual Properties of a Human‐specific and Microglia‐specific Siglec‐11 Transcript Variant
Authors: Chen Dillon Y. , Hane Masaya , Varki Ajit 
Published: April 2020

CD33‐related sialic acid‐binding immunoglobulin‐type lectins (Siglecs) are often found on innate immune cells and can modulate their reactivity. Previous studies showed that expression of the inhibitory Siglec‐11 in microglia is unique to humans and exists as an alternate splice form missing the exon encoding the last (5th) Ig‐like C2 set domain of the extracellular portion of the protein. Moreover, the brain‐enriched glycan polysialic acid (polySia/PSA) has been considered as a ligand of Siglec‐11. Here, we show that the human recombinant soluble microglial form hSiglec‐11(4D)‐Fc binds better to immobilized polySia than the tissue macrophage form hSiglec‐11(5D)‐Fc or chimpanzee cSiglec‐11(5D)‐Fc. We found that both intact and cleaved Siglec‐11 are in the culture medium, suggesting their ability to be secreted. Specifically, intact Siglec‐11 is found in exosomes and the microglial splice variant has reduced proteolytic cleavage and enhanced incorporation into exosomes. The exosomes bind to human neuroblastoma in a polySia‐dependent fashion. Mechanistically, cysteine palmitoylation is observed in the intracellular region and may regulate Siglec‐11 localization on lipid rafts and secretion on exosomes. Taken together, we demonstrate that hSiglec‐11(4D) is specifically expressed in human brain microglia and is released on the exosomes and/or proteolytic products, which have the potential to affect brain functions at a distance.Support or Funding InformationNational Institute of General Medical Sciences (NIGMS) R01GM32373
Tetanus Neurotoxin (TeNT) Traffics from PNS to CNS: Molecular Structure of the TeNT Receptor Binding Domain
Authors: Tiffany Karen A. , Bote Kayla , Fueger Kaitlyn , Gibeau Benjamin , Going Julia , Kunz Josslyne , Milton Grace , Novack Maya , Phelps Katelyn , Tiffany Benjamin , Voeller Henry , Sundeen Grace , Barbieri Joseph T. 
Published: April 2020

The World Health Organization reported that in 2017 almost 31,000 newborns died from exposure to tetanus neurotoxin (TeNT), which is produced by the bacterium Clostridium tetani, despite there being an effective vaccine available. When an individual is exposed to TeNT, the toxin travels through the bloodstream to the peripheral nervous system (PNS) where it is trafficked to the central nervous system (CNS). TeNT cleaves vesicle‐associated membrane protein‐2 (VAMP2), a membrane protein in the CNS, blocking the release of neurotransmitters which signal muscle cells to relax, thus resulting in spastic paralysis. TeNT has two separate domains, A and B. The A domain is a protease and the B domain contains both an N‐terminal translocation domain (HCT/T) and a C‐terminal receptor binding domain (HCR/T). HCR/T is made up of 450 residues, arranged into six alpha helices and 33 beta sheets. HCR/T has two important carbohydrate‐binding pockets. The Arg1226‐containing “R” pocket binds sialic acid on b‐series gangliosides (i.e. GT1b), while the Trp1289‐containing “W” pocket binds to sugar groups on a‐series gangliosides (i.e. GM1a). Functioning “R” and “W” pockets are essential for TeNT toxicity. The Cedarburg High School SMART (Students Modeling A Research Topic) Team has designed a model of HCR/T using 3D printing technology to investigate TeNT structure‐function relationships. Further investigation into how TeNT moves from the PNS into the CNS can help elucidate new methods to cure or prevent tetanus, especially in newborn infants in developing countries where the mortality rate is significant.Support or Funding InformationNational Institutes of Health Clinical and Translational Science Award (NIH‐CTSA UL1RR031973)
Extract From Yellow Passion‐Fruit (passilora edulis) Inhibits Prostate Cancer Cell Proliferation By TLR4/NFkB Pathway Regulation
Authors: Kido Larissa Akemi , Baseggio Andressa Mara , Rossetto Isabela Urra , Lamas Celina Almeida , Montico Fabio , Cagnon Valeria Helena Alves , Marostica Mario Roberto 
Published: April 2020

The yellow passion‐fruit (passiflora‐edulis) is rich in piceatannol (PIC), a polyphenolic and resveratrol analog known by its beneficial effects on health such as anti‐inflammatory anti‐cancer properties. The present study aimed to investigate the passion‐fruit extract (PFE) mechanistic of action in prostate cancer (PCa) cell lines with different genetic backgrounds and in the transgenic adenocarcinoma of the mouse prostate (TRAMP). For in vitro experiments, LNCaP (androgen‐responsive) and PC‐3 (androgen‐independent) cells were treated with different doses of PFE (125–500 μg/mL) and used for cell viability assay and western blotting analysis. For in vivo experiments, TRAMP mice were gavaged with 20mg/Kg of PIC contained in the PFE during 4 or 10 weeks of treatment. The ventral prostate was collected for light microscopy, immunohistochemistry and western blotting analysis. Because inflammation is intrinsically evolved with prostate alterations, like hormonal imbalance and cell survival, we focused on if PFE could affect these pathways. PFE treatment caused a significant reduction of cell viability in both cell lines tested, as well as decreased nuclear factor kappa B (NFκB) and toll‐like receptor 4 protein level. Interestingly, LNCaP cells were more sensitive to the PFE action in all experiments and we verified that the androgen receptor was markedly reduced by the treatment in these cells. PFE delayed CaP progression in the TRAMP model in both periods of treatment, significantly decreasing high‐grade prostatic intraepithelial neoplasia and well‐differentiated adenocarcinoma. These results were confirmed by the decrease of proliferating cell nuclear antigen immunostaining. Also, treatment with PFE reduced inflammation markers such as tumor necrosis factor‐alpha (TNF‐α), NFκB, and modulated negatively cell cycle regulatory protein levels and signal transducer and activator of transcription 3. Therefore, the results herewith showed that PFE was able to modulate disease progression through the inhibition of the inflammatory pathways, delay of the cell cycle, especially in the hormone‐dependent profile, demonstrating its chemopreventive and therapeutic potential in PCa.Support or Funding InformationSao Paulo Research Foundation ( Number: 2017/01573‐5)
Matrix Metalloproteinase‐9 Promotes Membrane Protrusive Activity in Ovarian Cancer Cells
Authors: Cook Nelson A. , Finnegan Katie D. , Kallenbach Reid A. , Lines Caleb L. , Ellerbroek Shawn M. 
Published: April 2020

Matrix Metalloproteinase‐9 (MMP9) is an extracellular endopeptidase associated with ovarian cancer development and progression. To further understand MMP9 contributions to metastatic behavior of an established ovarian cancer cell line (OVCA433), we utilized CRISPR to generate seven cell clones null for MMP9 expression. Analysis of the pooled clones revealed MMP9‐null cells exhibited identical phenotype and growth compared to parental OVCA 433 cells. Cell adhesion and transwell migration towards type I collagen was also not impacted by MMP9 loss. MMP9‐null cells were significantly delayed, however, in non‐directional filamentous actin‐based membrane protrusions on a variety of matrix substrates in response to Epidermal growth factor stimulation. Further, over or re‐expression of MMP9 in OVCA433 or MMP9‐null cells, respectively, was sufficient to drive both lamellipodial and filopodial membrane protrusions on glass. These results indicate MMP9 directly contributes to ovarian cancer protrusive activity.Support or Funding InformationWartburg Undergraduate Research Grants
FDA‐approved PARP Inhibitors are Cytoprotective against Cisplatin Injury in Renal Proximal Tubular Cells
Authors: Kim Jinu , Ha Ligyeom , Noh Mi Ra , Jang Hee-Seong , Padanilam Babu J. 
Published: April 2020

Cisplatin is a potent chemotherapeutic drug used to treat many solid cancers. However, its dose‐limiting side effect is nephrotoxicity, leading to acute kidney injury and chronic kidney disease. We previously reported that genetic or pharmacologicial inhibition of poly (ADP‐ribose) polymerase 1 (PARP1) protects against cisplatin nephrotoxicity.PARP1 inhibitors including olaparib, niraparib, and rucaparib are currently FDA approved for treatment of ovarian cancer. In this study, we tested the effect of the above FDA‐approved PARP inhibitors in cisplatin nephrotoxicity. Human HK‐2, pig LLC‐PK1, and mouse HUMPT renal proximal tubular cells (PTC) were subjected to one cycle of treatment with high‐dose cisplatin (1 to 1.5 mM) or four cycles of treatment with low‐dose cisplatin (1 to 3 μM). Each cycle consisted of 6 hours of treatment with cisplatin and 18 hours of recovery in cisplatin‐free medium. The FDA‐approved PARP inhibitors (300 pM to 1 μM) or the same volume of dimethylformamide (vehicle) were added immediately before the first treatment cycle and incubated continuously. The 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay performed to determine cell viability, lactate dehydrogenase (LDH) release assay to determine cell membrane disruption, and propidium iodide (PI) staining to determine necrotic cell death.All of the PARP inhibitors improved cell viability after the high‐dose cisplatin treatment in renal PTC. Increased percentages of LDH release and PI‐positive cells observed after one cycle of treatment with high‐dose cisplatin were significantly abrogated by the PARP inhibitors. Moreover, combined treatment with the PARP inhibitors showed an additive effect on cell viability in renal PTC treated with high‐dose cisplatin. The PARP inhibitors also enhanced cell viability after the four cycles of treatment with low‐dose cisplatin in renal PTC.Thus, our findings suggest that the FDA‐approved PARP inhibitors can protect efficaciously against death of PTC during cisplatin nephrotoxicity and could be developed as potential therapeutic agents to improve cisplatin nephrotoxicity.Support or Funding InformationThis study is supported by NIH grants DK‐116987, DK‐120533, AHA grants 15GRNT25080031 (BJP), 15POST25130003 (HSJ), and NRF grant NRF‐2019R1F1A1041410 (JK).