bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlation of Securin and Ki67 in Invasive Breast Carcinoma
Authors: Talaat Iman Mamdouh , Hamoudi Rifat Akram , Soliman Nada Mahmoud , Oweiss Nagwa Youssef , Omar Abbas Mohammed 
Published: June 2021

IntroductionApart from skin malignancies, breast cancer ranks the second most common malignancy in females worldwide. The increasing trends of breast cancer have led to plethora of studies in attempt to identify biological markers that may identify patients who may develop local recurrence or metastasis. Among those are proliferation markers which encompass ki67 and Pituitary Derived Tumour‐Transforming Growth Protein (PTTG).AimsTo identify the role of securin (PTTG) as prognostic marker in invasive breast carcinoma and its possible relation to ki67 and evaluate the use of ImmunoRatio® as a tool for calculating ki67 and labelling indices.MethodsSecurin and Ki67 immunohistochemical staining was performed on tissue microarray sections representative of 118 patients diagnosed with invasive breast carcinoma from 2005 to 2011. Assessment of immunohistochemical staining was carried out using both visual counting and ImmunoRatio®. The 118 cases were categorized into 2 groups according to their clinical outcome; the first group (G1) (n=77) comprised patients who were disease‐free while the second group (G2) (n=41) included patients who developed either recurrence and/or metastasis at the end of 24 months follow up duration.ResultsBoth securin and Ki67 labelling indices (LIs) obtained by visual counting were significantly higher in G2, while only securin LIs acquired by ImmunoRatio® were significantly higher in G2. Securin assessment by visual counting was the most accurate (AUC=0.775) in identifying patients who will likely suffer from recurrence or distant metastasis. Pearson correlation showed r=63.8%, p < 0.001 for Ki67 and r=67.1%, p <0.001 for securin. Linear regression analysis showed significant correlation between Ki67 and securin, B = 1.75, p < 0.001.ConclusionThe present results suggest that securin may have superior value to ki67 highlighting intra‐tumoural heterogeneity regions in invasive breast carcinoma patients' with poor clinical outcome. Better correlation between securin visual counting and ImmunoRatio® suggests that securin provides more uniform staining pattern than Ki67 in breast cancer.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Hybrid experimental‐mathematical methods for probing dynamic proteome organization during viral infections
Authors: Cristea Ileana M. 
Published: June 2021

Every year, a major cause of human disease and death worldwide is infection with the various viral pathogens that are intrinsic to our ecosystem. The outcomes of viral infections derive from dynamic virus‐host cell interactions that function either in promoting virus replication or in host defense against invading pathogens. An essential component of these virus‐host interactions is spatial organization. Eukaryotic viruses replicate within highly organized host cells that compartmentalize their vast cellular proteomes within organelles. Alterations in organelle shape, composition, function, and dynamics are prominent features of virus replication cycles, although the knowledge of the mechanisms involved remains limited.This presentation will describe the integration of experimental studies, mathematical modeling and inference methods for understanding the dynamic regulation of organelles during viral infection. The experimental methods presented will include live‐cell microscopy and quantitative mass spectrometry‐based proteomics for characterizing both organelle changes and virus‐host protein interactions during the progression of an infection. These studies discovered 1) dynamic changes in organelle composition, 2) translocation of cellular proteins from one subcellular compartment to another, and 3) temporal virus‐host protein interactions within organelles that induce alterations in host biological pathways (Figure 1).The value of these integrative methods is demonstrated by the identification of mechanisms through which viruses remodel subcellular organelle function to suppress host defense and promote viral replication. Furthermore, our findings are starting to uncover how viruses regulate the dynamics of organelle biogenesis during infection. Overall, these studies highlight how integrative omic technologies can help paint a picture of the pathogen's life cycle and aid in the future development of antiviral therapies.Support or Funding InformationNIH grants GM114141 and HL127640, and Mallinckrodt Scholar AwardThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Elevated Thrombospondin‐2 Contributes to Delayed Wound Healing in Diabetes
Authors: Kunkemoeller Britta , Kyriakides Themis R. 
Published: June 2021

Impaired wound healing is a major complication of diabetes and can lead to the development of chronic wounds in a significant portion of diabetes patients. Despite the risks posed by impaired healing, treatment strategies for diabetic wounds remain limited due to an incomplete understanding of the underlying pathological mechanisms. Previous studies have demonstrated that overexpression of thrombospondin‐2 (TSP2), a matricellular protein released after tissue injury, is associated with significant delays in dermal healing in various mouse models. Consistently, wounds lacking TSP2 (TSP2 KO) heal faster than wounds in wild‐type mice or mice with elevated TSP2. Thus, the present study aimed to examine the role of TSP2 in delayed healing in diabetes.First, we evaluated TSP2 expression in human wounds, and found that TSP2 is elevated in wounds from diabetes patients. Then, to determine TSP2's contribution to impaired healing in diabetes, we developed a novel diabetic TSP2 KO mouse model. Though these db/db TSP2 KO mice develop obesity and hyperglycemia comparable to db/db mice, db/db TSP2 KO mice exhibit significantly improved healing. Moreover, primary fibroblasts isolated from db/db TSP2 KO mice exhibit improved migration, providing mechanistic insight into the accelerated healing in these mice. We also studied TSP2 expression in fibroblasts, the major source of TSP2 in the wound, to explore the mechanisms leading to its overexpression in diabetes. Our results showed that TSP2 expression is increased in hyperglycemia, through increased activation of the hexosamine biosynthesis pathway and subsequent O‐GlcNAc modification of transcriptional elements. Overall, the results of this study indicate for the first time that: 1) TSP2 expression is elevated in diabetes and hyperglycemia and 2) TSP2 contributes to impaired healing in diabetes. These results represent a novel role for TSP2 in diabetes complications and a novel target for improving wound healing in diabetes.Support or Funding InformationNIH HL107205, NIH GM 072194, Gruber Science FellowshipThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Roles of GPR39, a Zinc‐Sensing Receptor, in the Regulation of Barrier Function of Intestinal Epithelial Cells
Authors: Chantivas Thanyatorn , Pongkorpsakol Pawin , Muanprasat Chatchai 
Published: June 2021

Zinc deficiency is associated with several gastrointestinal diseases such as diarrhea and IBD, whose pathogenesis is partly due to impaired intestinal barrier function. This observation suggests the beneficial role of zinc in regulating intestinal barrier function. The aim of this study was to investigate the effect of GPR39, a zinc‐sensing receptor, on intestinal barrier function and its underlying mechanisms. The results showed that treatment of T84 cell monolayers with TC‐G 1008, a GPR39 agonist significantly increased their transepithelial electrical resistance (TEER), indicating increased intestinal barrier function. The TC‐G 1008‐induced increase in TEER was in a time‐ and dose‐dependent manner. Moreover, co‐treatment with compound C, an AMPK inhibitor, completely abolished the effect of GPR39 agonist on TEER. This result suggests that AMPK may mediate the action of GPR39 agonist. In support of this notion, western blot analysis demonstrated that TC‐G 1008 time‐dependently induced AMPK phosphorylation, which reached its maximum at 2 hours paralleling the change in TER. Taken together, our results indicate that GPR39 activation can improve intestinal barrier function through an AMPK‐dependent pathway. This study provides an insight into the roles of GPR39 in the control of intestinal epithelial barrier integrity, which may be important for understanding pathogenesis or developing treatment of intestinal diseases.Support or Funding InformationThis work was supported by grants BRG5980008 from Thailand Research Fund and Mahidol University and Tonkla Ramathibodi Project from Faculty of Medicine Ramathibodi Hospital, Mahidol University.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Mapping Platelet Responses in Native American Populations
Authors: Stein Sarah J. , Rodezno Tania G. , Graber Katelyn N. , Hora Kirby A. , Clarke Santa M. , Pahlke Rachel S. , Abbott Karla M. , Larson Mark K. 
Published: June 2021

Platelets, key cellular components in normal hemostasis, can contribute to cardiovascular disease progression and are altered by certain drug therapies. These effects occur via a wide array of protein receptors that can respond to various in vivo signals and pharmaceutical products. Research has shown that the degree of platelet reactivity to either cellular signals or drugs may vary widely among individuals based upon the presence of receptor allele polymorphisms enriched within certain ethnicities. For example, African American populations have a variant in the thrombin receptor PAR‐4 that results in greater degrees of platelet activation and refractivity towards anti‐platelet medications compared to Caucasian populations (Edelstein et al., 2014, Blood 124: 3450–3458). As such, we novelly compared Caucasian and Native American populations by mapping platelet responses to five agonists that target distinct platelet receptors. Twenty‐five Native American subjects were studied along with age and sex‐matched Caucasian subjects. Flow cytometric analysis of platelet GPIIb/IIIa integrin conformational activation was used to measure the dose‐response effects of agonists on platelet activation, and SPSS was used to perform statistical analyses. Results showed that Native American subjects displayed higher levels of activation in response to lower doses of adenosine diphosphate (ADP) and thrombin receptor activating peptide (TRAP) compared to Caucasian subjects. However, no activation profile differences were observed following agonism of collagen, thromboxane, or von Willebrand factor receptors. This implies that medications targeting ADP and/or thrombin receptors could have varying responses in patients, or that those medications may not be optimal when treating patients with these receptor‐response variances. The data provide insight into possible platelet receptor variants between Native Americans and Caucasians that warrants further investigation.Support or Funding InformationResearch was supported in part by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health (P20GM103443), as well as funding from the National Science Foundation/EPSCoR program [IIA‐1355423], the state of South Dakota, and an undergraduate fellowship from the American Physiological Society.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Delineating the age‐related attenuation of vascular function: evidence supporting the efficacy of single passive leg movement.
Authors: Hydren Jay R. , Boxterman Ryan M. , Trinity Joel D. , Gifford Jayson R. , Kwon Oh Sung , Kithas Andrew C. , Richardson Russell S. 
Published: June 2021

Passive leg movement (PLM), performed continuously, is a promising clinically relevant assessment of peripheral vascular function which declines with age. To further refine PLM, this study evaluated the efficacy of a single PLM (sPLM) to delineate between young and old healthy males based on vascular function.MethodsTwelve healthy young (26±5 yr) and 12 old (70±7 yr) underwent sPLM: blood flow was assessed by Doppler ultrasound at baseline, during, and for one minute after a single leg movement (range of motion 90°). Blood pressure was continuously recorded by finger photoplethysmography. Factor analysis assessed covariance. If a significant age difference emerged, a cut score was determined by a receiver operator characteristic curve analysis. Data are mean±SD.ResultsAll blood flow and leg vascular conductance measures loaded into one factor (standardized loading ≥ 0.85), indicating the only physiological measure needed was blood flow. Baseline blood flows were similar between groups (p=0.626). Peak increase in blood flow from baseline was significantly attenuated in the old (Young: 717±227, Old: 260±97 ml·min−1, p<0.001; cut score: 485 ml·min−1, sensitivity 1, specificity 1) as was the total sPLM‐induced blood flow, above baseline, for 45 seconds (Young: 155±67, Old: 26±17ml, p<0.001; cut score: 72 ml, sensitivity 1, specificity 1).ConclusionsPLM, a simplified version of PLM, demonstrated strong qualities of a screening test for peripheral vascular function, evidenced by revealing the age‐related reduction in peripheral hyperemic response with clearly delineated cut scores. Indicating, sPLM has strong potential as an accurate screening test for age‐related attenuations in peripheral vascular function.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Standardizing the Isolation, Culture‐Expansion, and Cryopreservation of Canine Umbilical‐Cord Derived Mesenchymal Stromal Cells
Authors: Cromer Adrienne , Lillich James , Weiss Mark 
Published: June 2021

Mesenchymal stromal cells (MSCs) hold great promise in the field of regenerative medicine due to their ability to enable functional recovery in inflammatory injuries such as Crohn's disease and osteoarthritis. Currently, the MSC literature is focused on rodents for preclinical models of disease or clinical testing in human patients. We are interested in using the canine as a large animal model of human diseases. In this regard, the canine MSC literature lags behind human and rodent MSC, and most work on canine MSCs has focused upon bone marrow and adipose tissue‐derived with wide variation in isolation techniques. From surveying the literature and our pilot work, canine MSCs are more difficult to culture than human or rodent MSCs, have longer population doubling times, and earlier senesce. Here, a reproducible protocol for isolation and expansion of canine umbilical cord MSCs is provided. This method produces 10× greater yield per gram of tissue than other published methods. Gelatin‐coating of tissue culture plates greatly increases colony‐forming units‐fibroblast efficiency and decreases population doubling times. In addition, MSCs were able to be cultured longer before senescing, thereby increasing their cumulative population doublings. In summary, our understanding of the culture conditions needed for canine MSCs lags behind that of other species. Gelatin‐coating of tissue culture plates appears to be important for reproducible canine MSC culture. Currently, we are testing differentiation and characterization protocols to offer as standardized methods for the field.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Utilizing Social Networking Sites and Educational Videos in Public Outreach and the Classroom
Authors: Pena Angela , Brown Kirsten M. , DeVeau Kathryn M. 
Published: June 2021

A central priority for educators is to clearly convey information to their students and the public. However, it is often difficult to provide information in a concise and engaging way. This can be especially problematic when engaging with the general public. While people may have a thirst for knowledge, messages can get lost in translation when scientists focus on minutiae and/or jargon. To help communicate scientific concepts to students and the public in a more relatable way, teaching strategies such as creating infographics, narratives, and short videos are being widely utilized by the scientific community. With technology linking people together more readily than ever, scientists have a wealth of options to disseminate these materials. In the the last 20 years, social networking sites (SNS) have exploded both for personal and professional use. Due to their widespread reach, SNS are ideal platforms for communicating science to students and the public.The main objective of this project is to communicate anatomy concepts to students and the public in an engaging, easily digestible way by delivering the information through familiar media and SNS. We have created several short videos covering introductory anatomy concepts in order to provide students quality resources and study aids and to bridge the gap between scientists and the public. Based on format of the most popular scientific educators, we utilized the following criteria for our anatomy videos: 1. Videos should be under three minutes. 2. Videos should be visually pleasing. 3. Videos should focus on one or two concepts. Videos will be disbursed in class and advertised via SNS (e.g, Instagram and YouTube). We will also plan to disseminate the videos to schools in the DC area for students that may not have access to internet. To assess the efficacy of our videos, we will use social media metrics (i.e., reach, views, etc.) from the SNS, as well as data from student surveys. These data will be analyzed and used to tailor future videos and better guide us on how to communicate science more effectively.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Longitudinal Changes in Facial and Basicranial Integration in the Mediolateral Axis
Authors: Miller Steven F. , Welling Andrew , Holton Nathan E. 
Published: June 2021

ObjectivesMany studies over the past decade have employed morphological integration as a framework for understanding the interaction of the facial and basicranial skeleton in humans, the great apes, and our fossil lineage. Fewer studies, however, have examined morphological integration in the facial and basicranial portions of the skull in a true longitudinal sample. Most of these longitudinal studies have focused primarily on lateral cephalograms. While useful, these datasets only examine shape and morphological integration from the lateral aspect, limiting the types of questions that can be explored, primarily in the mediolateral axis. To rectify this gap in the data, we set out to study aspects of both symmetric and asymmetric shape variation in a longitudinal postero‐anterior (PA) celphalometric dataset in order to ascertain how patterns of morphological integration change in the mediolateral plane as a function of growth.MethodsPA cephalograms from a total of 55 individuals from the longitudinal Iowa Facial Growth Study were digitized using 13 coordinate landmarks across the mandible, face, and cranial base to capture patterns of integration and modularity. This data was collected at three time points per patient: age 4, age 11, and in adulthood. Data were submitted to MorphoJ for a Two‐Block Partial Least Squares (2‐B PLS) analysis of both the symmetric and asymmetric shape components in order to examine morphological integration between the face and cranial base.Results2‐B PLS results for the symmetric shape component show that integration between the face and cranial base decrease (becoming more modularized) from age 4 (RV=0.41, p<0.001), to age 11 (RV=0.25, p<0.001) before increasing again at the adult time point (RV=0.35, p<0.001). For the asymmetric component, however, levels of integration between the face and basicranium decrease consistently from age 4 (RV=0.59, p<0.001) to adult (RV=0.47, p<0.001). These results indicate that while levels of cranial integration tend to decrease throughout growth, this decrease is only consistent in the asymmetric shape component, potentially indicating that modularity of the face and cranial base has a strong mediolateral (side‐to‐side) component.ConclusionThese results show that while overall trajectories of facial/cranial base integration show a similar trend toward modularity as individuals grow, this pattern of modularity is only a linear when examining the asymmetric shape component. This aspect of shape has been largely overlooked in the integration literature to date and warrants further study.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 Role For The Transcription Factor SNAIL In Alternative Splicing
Authors: Rudraraju Smruthi , Kumar Janani , Krueger Shawn , Qureshi Humaira , Scheidegger Adam , Dhasarathy Archana 
Published: June 2021

The transcription factor SNAIL is one of the key regulators of an early developmental process called the Epithelial to Mesenchymal Transition. This process is characterized by a cell‐state change from a highly differentiated, epithelial phenotype to a less differentiated, migratory mesenchymal phenotype. SNAIL binds to E‐box motifs in promoter regions and recruits chromatin remodelers to repress or activate gene expression. To identify proteins associated with SNAIL, we used co‐immunoprecipitation of SNAIL‐bound proteins followed by mass spectrometry. A large number of splicing proteins associated with SNAIL, including SRSF1, a regulator of alternative splicing.Co‐immunofluorescence and co‐immunoprecipitation data from our lab indicate that SNAIL associates with splicing protein SRSF1. Further, SNAIL co‐immunoprecipitated with SRSF1 in the presence of DNase, but not in the presence of RNase, indicating that the SNAIL‐SRSF1 association is RNA‐dependent. Knockdown of SNAIL with siRNA resulted in loss of mesenchymal splice isoforms and reversion to epithelial specific isoforms. RNA Immunoprecipitation of SNAIL‐ and SRSF1‐ associated RNAs showed increased enrichment for mesenchymal specific isoforms of mRNAs, suggesting that SNAIL and SRSF1 influence alternative splicing.We hypothesize that SNAIL regulates alternative splicing by binding to RNA and recruiting SRSF1. We are currently investigating genome‐wide changes in alternative splicing regulated by SNAIL, and working to understand the mechanism by which SNAIL interaction with the spliceosome leads to alternative splicing. As transcription and splicing are closely coupled, we predict that transcription factor regulation of splicing through RNA binding is universally utilized by other biological systems to alter phenotype in response to external stimuli.Support or Funding InformationUniversity of North Dakota, NIH Grant #1P30GM103329 and NIH COBRE #P20GM104360‐01This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.