bluuebunny/crossref_metadata_2025_split huggingface dataset:
Link between food intake and the expression of O‐linked N‐acetylglucosamine Transferase (OGT) in channel catfish
Authors: Abernathy Oaklee , Dougherty Megan , Kostner Danica , Nevarez Ericka , Schmidtberger Abigail , Spainhour Rebekah , Kobayashi Yass 
Published: June 2021

The obesity epidemic in the United States has been a serious concern for many years and has driven researchers to determine genetic mechanisms that might contribute to its development. In mice, O‐linked N‐acetylglucosamine Transferase (OGT) might serve as a satiety factor responsible for controlling food intake and body weight. OGT appears to signal “fullness” to the brain, and decreased OGT expression leads to weight gain and development of an obese phenotype. In a previous study, OGT expression was examined in various tissues of channel catfish. OGT mRNA was detected in all sampled tissues, with the brain having the highest expression. Our previous study also showed that prolonged fasting appeared to decrease the expression of OGT mRNA in the brain. To determine how feeding frequency correlates with the expression of OGT mRNA in catfish, we completed a 28 day feeding study with three feeding frequencies. Fish were fed every 12 (overfed), 24 (control), or 48 (underfed) hours (n= 4 tanks per treatment, 8 fish per tank). Brain samples were collected from two juvenile catfish from each tank. Using quantitative RT‐PCR, the expression of OGT mRNA was examined in the brain samples. The expression of all OGT mRNA transcripts, as well as the expression of OGT X1 and X3 variant mRNA were not affected by feeding frequency, suggesting changes in feeding frequency might not directly influence OGT mRNA expression in the brain. We are currently examining the relationship between feeding frequency and OGT mRNA expression in the liver.Support or Funding InformationThis project was partially supported by a grant (P20GM103418) from Kansas IDeA Networks of Biomedical Research Excellence (K‐INBRE) of National Institute of Health (NIH).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Probing the Two Orientations of Pal in Vesiculating E. coli
Authors: Pannullo Nicole , Zavorin Mark , D'Arcy Brooke , Farquharson Kara , Kaur Ravinder , Surendran Naveen , Pichichero Michael , Hellman Judith , Michel Lea Vacca 
Published: June 2021

Peptidoglycan associated lipoprotein (Pal) is an outer membrane protein from Gram‐negative bacteria, including Escherichia coli (E. coli). E. coli has two subpopulations of Pal: a periplasmic subpopulation bound to peptidoglycan and a surface exposed subpopulation. When the bacteria are cultured under normal conditions in rich media, only a small percentage of cells contain surface exposed Pal. Under more stressful culture conditions (ex. increased temperature, the presence of antibiotics), E. coli will release outer membrane vesicles (OMVs). Using ultracentrifugation and immunoblotting, we have shown that Pal is released from E. coli in these OMV's. We also used flow cytometry to measure the surface exposed Pal subpopulations in hyper‐vesiculating E. coli cells and their OMVs. Preliminary data suggest that the surface exposed Pal subpopulations are increased in vesiculating cells and OMVs.Support or Funding InformationReceived: Rochester Institute of Technology FEAD grant to Dr. Lea Vacca Michel Applying for: RIT Honors program $500 travel stipend to Nicole Pannullo Applying for: RIT National Technical Institute for the Deaf Student Travel Award to Nicole PannulloThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Engineering synthetic glycan co‐receptors into the glycocalyx of muscle cells to control early stages of neuromuscular junction development
Authors: Godula Kamil 
Published: June 2021

Glycans (also known as carbohydrates, saccharides or, simply, sugars) are among the most intriguing carriers of biological information in living systems. The structures of glycans not only convey the cells' physiological state, but also regulate cellular communication and responses by engaging receptors on neighboring cells and in the extracellular matrix. Despite their structural complexity, individual glycans rarely engage their protein partners with high affinity. Yet, glycans modulate biological processes with exquisite selectivity and specificity. To correctly evaluate glycan interactions and their biological consequences, one needs to look beyond individual glycan structures and consider the entirety of the cell‐surface landscape. There, glycans are presented on protein scaffolds, or are linked directly to membrane lipids, forming a complex, hierarchically organized network with specialized functions, called the glycocalyx. In this presentation, I will describe our studies toward engineering the glycocalyx of differentiated myotube cultures to present co‐receptors for the nerve‐derived synaptogenic signal, agrin, aimed at obtaining control over organization of acetylcholine receptors in the postsynaptic terminals of developing neuromuscular junctions.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The heparan sulfate degrading enzyme heparanase is up‐regulated by the EWS‐Fli1 fusion protein in Ewing sarcoma
Authors: Gaskin Shaun 
Published: June 2021

Ewing sarcoma is an aggressive form of bone and soft tissue cancer that predominantly affects adolescents. It is commonly caused by the partial translocation of the Ewing sarcoma protein (EWS) gene to the gene encoding the Ets family transcription factor Fli1, resulting in the formation of the EWS‐Fli1 fusion protein. Ewing sarcoma is often highly metastatic, resulting in a poor survival rate of approximately 20%. Expression of the endoglycosidase heparanase (HPSE), a heparan sulfate‐degrading enzyme that contributes to extracellular matrix remodelling, is up‐regulated in approximately 90% of all cancers, including Ewing sarcoma, and possesses pro‐metastatic and ‐angiogenic functions. It is therefore not surprising that it is also a marker of poor prognosis for cancer patients. While increased expression of HPSE in Ewing sarcoma has been reported to correlate with increased tumour size, disease severity and a poor patient outcome, the mechanism by which HPSE expression is increased in Ewing sarcoma has not been defined. We have identified a novel link between the EWS‐Fli1 fusion protein and the expression of HPSE. Using a combination of patient‐derived samples and cell lines, we have been able to show that an increase in expression of EWS‐Fli1 correlates with increased HPSE expression and activity. We also demonstrated that increased EWS‐Fli1 expression is responsible for increased HPSE expression and enzymatic activity by binding to the HPSE gene promoter and driving its expression. These findings highlight a possible role for HPSE in the progression and prognosis of Ewing sarcoma that may contribute to the aggressive nature of the disease.Support or Funding InformationAustralian National Health and Medical Research CouncilThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Preclinical evaluation of a new ROS1 inhibitor to overcome resistance to EGFR therapy in glioblastoma
Authors: Aljohani Hashim M. , Bahassi El Mustapha 
Published: June 2021

Glioblastoma Multiforme (GBM) is the most aggressive brain tumor in adults and remains incurable despite multimodal intensive treatment regimens. The majority of GBM tumors show a mutated or overexpressed Epidermal Growth Factor Receptor EGFR; however, tumors treated with EGFR inhibitors such as gefitinib or erlotinib inevitably recur. This recurrence highlights the need to identify signaling pathways involved in GBM resistance to EGFR therapy that may serve as targets for intervention. In our recently published work, we found that activation of the ROS1 pathway is a primary mechanism by which glioma cells become resistant to EGFR‐targeted therapy. ROS1 is a proto‐oncogene receptor tyrosine kinase activated by chromosomal rearrangement in several human cancers, including non‐small‐cell lung cancer (NSCLC), cholangiocarcinoma, gastric cancer, ovarian cancer, and glioblastoma. We therefore, designed, synthesized and screened a series of new ROS1 inhibitors. The lead compound, ROS‐Ic, is very potent (IC50 = 24nM) and highly specific to ROS1 protein. Treatment of gefitinib‐resistant GBM cells with ROS1‐lc sensitized the resistant cells to low concentrations of gefitinib resulting in apoptosis following a prolonged S phase cell cycle arrest. When compared to Crizotinib, an FDA‐approved small‐molecule tyrosine kinase inhibitor currently used to treat ALK‐ and ROS1+ NSCLC patients, ROS‐Ic showed superior cytotoxic activity in vitro towards ROS1‐positive GBM cells. Crizotinib resistance is thought to be due to diminished Crizotinib binding, due to ROS1 mutations in Crizotinib binding pocket. Interestingly, our initial analysis suggests that our lead compound ROS1‐Ic might not be affected by these mutations, highlighting the potential therapeutic value of this compound.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
A High‐throughput Targeted Bisulfite Sequencing‐based Analysis for Epigenetic Age Quantification and Monitoring
Authors: Chew Yap Ching , Guo Wei , Yang Xiaojing , Jin Mingda , Booher Keith , Horvath Steve , Jia Xi Yu 
Published: June 2021

Aging represents the most important risk factor for many chronic diseases including cardiovascular diseases, diabetes, and cancer, therefore understanding the mechanisms of aging is a fundamental step for designing new treatments for chronic diseases. DNA methylation is the most reliable and accurate molecular marker for aging quantification, however, genome‐wide DNA methylation profiling techniques, such as reduced representative bisulfite sequencing and Illumina Bead Array that are widely used in aging research are prohibitively expensive and have poor data quality at low‐read coverage sites. Here we report a robust targeted bisulfite sequencing approach, called SWARM™ (Simplified Whole‐panel Amplification Reaction Method), for the accurate biological age determination. SWARM™ is flexible and low cost, requires relatively low DNA input, allows the simultaneous amplification and sequencing of hundreds of loci, and has shown to increase sample throughput. Using the SWARM™ approach, we were able to analyze the methylation level of several hundreds of age‐associated loci including the published Horvath Clock sites. An age‐predictive model was built using the elastic net regression of DNA methylation levels of the loci and chronological age of blood DNA samples of over 300 healthy subjects of 18 to 89 years old. Our epigenetic age (DNAge™) predictor achieved a small median age error, and the DNAge™ of samples that were processed on both sequencing and array platforms highly correlated (r > 0.9). In brief, our versatile SWARM™ technology‐based DNAge™ platform is a very fast and accurate tool for the precise biological aging quantification and aging interventions monitoring. Dedicated DNAge™ platforms are compatible with various sample types, and can be applied for aging studies in human, and in other species including mice.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Prevalence of 22q11.2 Deletion and Genetic Characterization in Chinese Patients with Congenital Heart Disease
Authors: Hou Hai‐Tao , Chen Huan‐Xin , Wang Jun , Yuan Chao , Wang Xiu‐Liu , Yang Qin , He Guo‐Wei 
Published: June 2021

BackgroundThe 22q11.2 deletion syndrome, resulted from the rearrangements in the 22q11.2 chromosomal region, is the most common microdeletion syndrome. Most patients share a common 3Mb or 1.5Mb hemizygous deletion of 22q11.2 in the low copy repeats (LCRs). The remaining patients include smaller deletions that are nested within the 3Mb typically deleted region (TDR) and a few rare deletions that have no overlap with the TDR. The present work aimed to identify the prevalence and the detailed genetic characterization of 22q11.2 deletion or amplification in the children with any sporadic congenital heart disease (CHD), and to explore the genotype‐phenotype relationship between deletion/amplification type and clinical data.MethodsA total of 354 CHD patients were screened by multiplex ligation‐dependent probe amplification and capillary electrophoresis methods. Universal Probe Library technology was applied to validate the screening results.ResultsWe found 40 patients in 354 CHD (11.3%) carried different levels of deletions or amplifications. The phenotypes of the 40 patients included ventricular septal defect (15), atrial septal defect (12), patent ductus arteriosus (12), tetralogy of Fallot (6), right ventricular outflow tract stenosis (4), pulmonary stenosis (2), pulmonary hypertension (18), and Down's syndrome (2). Two patients with ventricular septal defect carried the 3Mb TDR from CLTCL1 to HIC2 (LCR A–D) and 1.5Mb deletions from CLTCL1 to MED15 (LCR A–B) respectively; all the others carried atypical deletions or amplifications nested within the LCRs. Based on the gene analysis, CDC45 (15), TBX1 (8), USP18 (8), RTDR1 (7), SNAP29 (6), and ZNF74 (4) exhibited a higher incidence among the 40 individuals; in addition, 6 patients presented a amplification in TOP3B gene.ConclusionsThis study revealed 3Mb TDR, smaller deletions, rare deletions, and segmental amplifications of chromosome 22q11.2 in Chinese CHD patients. The genotype‐phenotype relationship analysis indicated that those gene abnormalities may cause various types of CHD. Our data also suggest that genetic detection should be performed routinely in CHD patients and the unique deletions or amplifications may provide useful insight into individual analysis.Support or Funding InformationSupported by grants from the National Natural Science Foundation of China (81170148 & 81641017), Zhejiang Provincial Natural Science Foundation (LY15H020008), & Tianjin Binhai Key Platform for Creative Research Program (2012‐BK110004), Binhai New Area Health Bureau (2012BWKZ008, 2016BWKY007, 2016BWKZ003).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
MINIMAL EFFECT OF ALISKIREN ON MAST CELLS COUNT AND RENAL VASCULAR DAMAGE IN ACUTE RAT MODEL OF TRIOLEIN INDUCED PULMONARY FAT EMBOLISM.
Authors: Khalafi Farnaz , Onishchenko Elizabeth , Pour Mohammad , Arif Dauod , Monaghan Paula , Poisner Alan , Molteni Agostino 
Published: June 2021

IntroductionIn a rat model of fat embolism (FE) induced by injection of triolein (T) a severe inflammatory reaction leads to vasoconstriction and pulmonary fibrosis (1). Mast cell numbers are significantly increased in the lungs of the treated animals (2), and mast cell inhibition improves pulmonary vascular remodeling in pulmonary hypertension (3).There is evidence that the renin angiotensin system (RAS) is involved since drugs related to this system: captopril, losartan and aliskiren, prevent the pulmonary vasculitis and fibrosis in the early phase (48 hours) (4,5). However, aliskiren (ALI), a direct renin inhibitor, had a minimal effect on renal vasculitis, and fibrotic changes (6). In this study we evaluated the effect of T and ALI on renal mast cells.Materials and methods22 Sprague Dawley rates (250–300g BW) received T (0.2 ml n=18) or saline n=4. The T treated rats, divided into 3 groups of 6 each, were IP injected one hour later either with 0.2 ml saline, ALI 50 mg/kg or AL I 100 mg/kg. Four controls received saline.48 hours later rats were killed under isoflurane anesthesia and the kidneys and lungs stained with H&E, Trichrome, SMA1 for inflammation and fibrosis, and CD117 for mast cells. 10 photographs at 200× were taken for slides of each organ by two pathologists unaware of the slides' identity, mast cells were counted and pathological damage evaluated.ResultsRenal fibrosis and vasculitis were irrelevant by observation with all SM1, Trichrome or H&E stains, with the exception of the media adventitia ratio (MAR) of arteries (p= 0.007) which significantly increased after T‐saline treatment but not after ALI administration. These findings are in contrast with the observations of the lungs where the damage was severe and reduced by both ALI doses. Kidneys of ALI 100 mg/kg treated rats were similar to those ones of T+Saline or of the controls. Although a mild mast cell increase was noted in kidneys of T+Saline treated animals, no statistically significant difference in mast cells was observed.ConclusionRenal findings were quite different from our lung findings in either histopathological damage or mast cell accumulation. The study suggests that the RAS system influence on the kidneys differs from that of the lung at this acute stage of fat embolism.Support or Funding InformationSupported by the Catherine T Geldmacher Foundation, St. Louis, MOThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Fractones: tumor matrix in colon cancer, stomach cancer and glioblastoma
Authors: Mercier Frederic , Uguen Arnaud , Marcorelles Pascale , Fronville Alexandra , CORCOS Laurent 
Published: June 2021

The basic pathological mechanisms leading to dysplasia, tumor progression and the destruction of adjacent tissues are not well known. Basement membranes and underlying connective tissue are part of the construction machinery that operates to form structures during development and throughout adult life. In cancer, basement membranes tend to restructure the tissue in conjunction with altered stem cells and their microenvironment‐specific extracellular niche. We have characterized a new type of extracellular matrix that we have named fractones. Fractones are chemically similar to basement membranes and consist at least of laminin isoforms, collagen‐IV, nidogen and heparan sulfate proteoglycan. However, fractones and basement membranes differ with respect to their location. Fractones reside in the parenchyma of tissues and organs and are visualized as particles by light microscopy whereas they often display a fractal ultrastructure (a reference to their name). In contrast, basement membranes form sheaths at the connective tissue/parenchyma interface and in between the layers of the vascular wall. We have shown that fractone‐associated heparan sulfates bind, concentrate and activate the FGF‐2, BMP‐4 and BMP‐7 growth factors to regulate stem cell proliferation in the neurogenic zone of the adult brain. Here, we hypothesized that fractones are produced by cancer stem cells and by their immediate progeny to bind and concentrate growth factors to their vicinity. This would participate in rerouting the activity of the physiological stem cell niche and benefit from neovascularization to capture essential nutrients and reach independence. Using immunohistochemistry for laminin, a marker of fractones and basement membranes, on sane and cancerous tissues, we have identified deficient basement membranes and a high expression of fractones in zones without basement membranes in colon cancer. In addition, a high ectopic expression of fractones was correlated with a significant decrease in vasculature in multiform glioblastoma. Our results show that fractones are associated with cancer‐specific morphological alterations. We anticipate that the alteration in binding of growth factors in cancer tissues could ultimately lead to increased proliferation coupled with a distorted neoangiogenesis. These results provide novel insights into hitherto unrevealed mechanisms, on which innovative future therapies may be based, for example using glycan antagonists of those expressed in tumor‐specific fractones.Support or Funding InformationCanceropole Grand Ouest, FranceThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Indoleamine 2,3‐dioxygenase expression is correlated to prognosis in localized prostate cancer.
Authors: Ferreira Janaina Mendes , Pontes‐Júnior José , Matheus Luiz Henrique Gomes , Sousa Diego Mota , Lima Amanda Eunice Ramos , Almeida Robson José , Camacho Cleber Pinto , Reis Sabrina Thalita , Leite Kátia Ramos Moreira , Srougi Miguel , Dellê Humberto 
Published: June 2021

BackgroundIndoleamine 2,3‐dioxygenase (IDO) is an enzyme that acts as an immunomodulatory molecule. It is found in several cancer types where it seems to be associated with tumor escape due to its immunosuppressive mechanisms. Some studies have reported a correlation between carcinogenesis and changes in IDO expression. However, the role of IDO expression in prostate cancer (PC) is unclear. The aim of our study was to evaluate the expression of IDO in localized PC, and to correlate its expression with the classic prognostic factor and recurrence after surgical treatment.MethodsFor this case‐control study, we retrospectively evaluated surgical specimens from 111 patients with localized PC, who underwent radical prostatectomy. Recurrence was defined as a prostate specific antigen (PSA) level exceeding 0.2 ng/ml postoperatively, and the median follow‐up was 123 months. IDO expression was evaluated by immunohistochemistry in 72 cases of which 42 (58%) had biochemical recurrence.ResultsWe found that lower IDO expression was associated with higher Gleason score (p = 0.022) and PSA levels (p = 0.042). The multivariate analyses revealed that the loss of IDO expression and higher PSA levels were independently associated with biochemical recurrence. The chance of recurrence was increased by 85% in patients with lower IDO expression (OR = 0.15; p = 0.009 CI 95% [0.038–0.633]) and increased by 5.5 times in patients with higher PSA levels (OR = 5.51; p = 0.012 CI 95% [1.435–21.21]). The recurrence‐free survival curve also demonstrates that lower IDO expression (p = 0.0004) was associated with lower time to biochemical recurrence.ConclusionThe loss of IDO expression was associated with increased chance of biochemical recurrence, higher PSA, and a Gleason score in localized PC.Support or Funding InformationThe study was supported by São Paulo Research Foundation (FAPESP)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.