bluuebunny/crossref_metadata_2025_split huggingface dataset:
Understanding the structure and function of cone snail insulin as a substitute for human insulin
Authors: Lane Jim , Firminger Makayla , Fraser Emily , Geiger Mya , Morris Sydney , Ryan Marin 
Published: June 2021

It is estimated that more than 415 million people currently have diabetes. Diabetes is an inability to properly regulate and/or produce insulin. Insulin dependent diabetics need to inject themselves with insulin in order to eat, drink, and function properly. Current insulin activation is around fifteen minutes but can take up to 90 minutes to fully activate. Cone snail insulin (CSI) appears to have the ability to fully activate within minutes. Rapid activation can prevent the body from spending long periods of time in a hyperglycemic state (too much sugar in the bloodstream). Long periods of time in a hyperglycemic state can cause damage to blood vessels and nerves, which in turn, leads to damage to the entire body. The goal of this research process was to discover why and how CSI binds to the receptors and how to mimic this behavior to decrease the activation time of insulin in the human body. The exploration phase of this research inquired how CSI would potentially bind with human insulin receptors and determine if it would be possible to mimic this to use in diabetic patients to decrease the activation time. During the modeling phase of this project, JMOL was used to compare the molecular structures and functions of CSI and human insulin in order to establish if CSI would be interchangeable with human insulin. Cone snail venom contains insulin which causes a hypoglycemic sedation, paralyzing its victim on contact. While researching this process, it was discovered that the B‐chain on the CSI protein is missing the amino acid residues from B23–B30. Human insulin, when stored in the pancreas, aggregates into dimers. These dimers group together to form hexamers. Injected insulin is also in dimer form, but it needs to disaggregate in order to become effective. One human insulin molecule binds to the other using hydrogen bonds on the amino acid residues from B23–B30. Because CSI is missing this portion, it can enter the bloodstream without aggregating. In order to mimic the function of the CSI in humans, human insulin needs to be modified to eliminate the aggregation of insulin cells in the human body. To do this the Mahtomedi High School team, Mahtomedase, MSOE Center for BioMolecular Modeling MAPS Team used 3D modeling and printing technology to examine structure‐function relationships between CSI and human insulin. Current insulin activation time can take, at minimum, fifteen minutes. CSI has the potential to increase reaction time by upwards of 200 percent by more readily binding to the human insulin receptor.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Human Insulin vs Genetically Engineered Fast Acting Insulins
Authors: Mukhtar Farzan , Veljkovic Petar , Melnyk Max , Smetanin Yakov , Gong David , Lawal Dayo , Drohomyrecky Michael , Mingolelli Gabrielle 
Published: June 2021

Insulin is a protein produced in the pancreas. The primary function of insulin is to regulate the levels of glucose in the body from food that is consumed. When food is consumed, beta cells in the pancreas, the body is signalled to release insulin. The insulin that is released binds to insulin receptors, which then cause glucose transporters to be inserted in the membranes of different cells. The glucose transporters allow the cells to take in glucose from the bloodstream, and be used for energy for the body, or be stored for later use as glycogen.Individuals with diabetes are not able to produce sufficient insulin in the pancreas to keep blood glucose levels low, leading to health problems. One treatment for diabetes is to use insulin medication to control blood glucose levels. Due to the need for insulin medication which quickly takes action and lowers the blood glucose levels of diabetes patients, fast‐acting insulin was developed as a medication option. The structural differences between fast‐acting insulin medication, and insulin that is produced naturally in the pancreas are what cause the two proteins to function differently.Insulin lispro, which was the first genetically engineered rapid acting insulin, has a slight difference in the B chain than human insulin, where the proline at position 28 is switched with lysine at position 29, resulting in a lower capacity of self association in a solution, which results in a faster absorption, higher peak serum levels, and a shorter action duration than human insulin. Insulin aspart, another form of fast acting insulin, is structurally different from human insulin, in that the proline at position 29 is switched with a charged aspartic acid resulting in it being absorbed twice as fast as human insulin. Insulin glulisine, the most recently created fast acting insulin, is different in structure from human insulin because the asparagine at position 3 is replaced with lysine, and the lysine at position 29 is replaced with glutamic acid, which results in a reduction in hexamer formation and an enhanced absorption from subcutaneous depots. These differences in structure between the three different types of fast acting insulins and human insulin will be directly pointed out with the models of the different insulin types which will be created.Support or Funding InformationFunded generously by Chicago Public Schools, the Cless Family Foundation, Friends of LIncoln Park High School, and the Center of Biomolecular Modeling at Milwaukee School of Engineering.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Insulin, You're Confusing the Systems
Authors: Bartolomei Barrett A , Mergens Steven Ryland , Love Ryan Ann , Shipley Ashley Willow , Martinez Sandra Ann 
Published: June 2021

Insulin is a protein (hormone) that changes conformation to engage its receptor. In 2015 it affected an estimated 1.6 million deaths due to high blood glucose, from diabetes. Inability for insulin to bind to its receptor ultimately leads to the overabundance of glucose. This overabundance then leads to mitochondrial stress in pancreatic beta cells causing unwanted beta cell apoptosis and dysfunction. One component of the insulin change is the decrease in insulin sensitivity in the bloodstream due to glucose overexposure. Insulin becomes resistant to hormonal stimulation suggesting a change in the C‐terminal B‐chain segment. This conformational change insulin undergoes exposes the side chains IleA2, ValA3, ValB12, PheB24, and PheB25 to allow insulin to bind to its receptor. A further understanding of how the native folding is preserved and the binding sites that are blocked are opened, can open opportunities for additional clinical mutations in the insulin family and provide a basis for new research and therapeutic drugs, possibly leading to a more regulated interaction between insulin and glucose.Support or Funding InformationPDB: 4OGA Primary Citation: Protective hinge in insulin opens to enable its receptor engagement. Menting, J.G., Yang, Y., Chan, S.J., Phillips, N.B., Smith, B.J., Whittaker, J., Wickramasinghe, N.P., Whittaker, L.J., Pandyarajan, V., Wan, Z.L., Yadav, S.P., Carroll, J.M., Strokes, N., Roberts, C.T., Ismail‐Beigi, F., Milewski, W., Steiner, D.F., Chauhan, V.S., Ward, C.W., Weiss, M.A., Lawrence, M.C. (2014) Proc.Natl.Acad.Sci.USA 111: E3395–E3404 The El Capitan High School CBM MAPS Team used 3‐D modeling and printing technology to examine structure‐function relationships of insulin.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Structure Analysis and Phenotype of the PTF1‐J/Ptf1a P191T Mutant Heterotrimeric Complex
Authors: Coats Ward , Ali Nor , Ali Arham , Davies Latham , Sterling Jewel , De Leon Luis , Sandoval Ernesto , Pacheco Ariadne , Montes Kristen , Guerrero Ingrid , Jordan Emily , Mulley Alexander 
Published: June 2021

The Hillcrest High School Biomedical Research Program in Dallas, Texas, studies the PTF1‐J and PTF1‐JL heterotrimeric complexes. The complexes are composed of a common E‐box binding protein, Ptf1a and RbpJ or RbpJL. These complexes are transcriptional master regulators of pancreas development. PTF1‐J is required for early pancreas development. During the secondary transition of pancreas development RbpJ is replaced by RpbJL. The PTF1‐JL complex is required for the mature acinar cell phenotype. In the current study we have performed structural modeling using Pymol and Jmol of the PTF1‐J and PTF1‐J/Ptf1a P191T complexes. Children born without a functional Ptf1a protein lack a pancreas, are severely diabetic and require immediate medical intervention by administering insulin to maintain blood glucose homeostasis and or enzyme therapy to provide digestive enzyme activity in the small intestine for nutrient uptake into the bloodstream. In the current study we have performed structural modeling of the PTF1‐JL/Ptf1a P191T complex and used 3‐D printing technology to generate a model that may help explain the loss of function resulting in pancreatic aplasia in children born with this mutation.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Augmented Reality as an Educational Tool for Teaching Macromolecular Structure and Function
Authors: Sung Rou‐Jia , Wilson Andrew , Crowl Logan , Nardi Joseph , St. Clair Katie 
Published: June 2021

Relating macromolecular “structure to function” is considered a foundational skill in biochemistry and molecular biology course curriculums. The molecular visualization skills necessary to interpret information in 3D models of biological macromolecules, however, are often lacking. Moreover, current technologies aimed at spanning this skills gap often require varying degrees of prior knowledge, training, and/or hardware requirements that can make implementation difficult. To address this we have developed a simple classroom activity using augmented reality technology that allows students to quickly and easily interact with high‐resolution images of a 3D macromolecule. The activity was implemented in a junior/senior level biochemistry course as part of a class discussion on the structure and function of the potassium channel. The 3D images were integrated as an iPad application in which a 3D virtual image of the molecule would appear superimposed on the real world on the iPad screen when the iPad camera was directed towards a printed QR code. Students were able to rotate, translate, and zoom in on the molecule by physically moving either the iPad or the QR code sheet. The activity was also accompanied with worksheet questions aimed at developing an interpretation of the 3D structure. Student attitudes were assessed using a pre/post survey analysis. Results indicate increases in student confidence towards visualizing the 3D structures of biological macromolecules, as well as an increase in positive student perceptions of the helpfulness of looking at 3D structures for learning protein biochemistry.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 Survey Course for STEM Students to Understand Diversity and Inclusion Through Readings, Discussion and Reflection.
Authors: Benore Marilee Ann , Smith Sheila R 
Published: June 2021

Scientific discovery, innovation and success are enhanced when diverse groups participate.Promoting diversity and inclusion requires understanding both obstacles and best practices. One way to achieve success is to ensure that students in STEM fields recognize bias, understand why a diverse workforce is critical, and know how to support diversity and inclusion.This hybrid class is an overview of gender in science in engineering. Weekly lectures and in‐class discussion coupled with online discussion with peers are critical components of student learning. The topics include STEM statistics, best practices, research, implicit bias, a brief history of women in STEM, feminist theory, and the science of sex and gender. An emphasis that opinions and statements must be supported by factual references. Primary literature, videos, guest lecturers, interviews, books and white papers are used as sources. The final student project is a proposal to create change via outreach, education, policy or research.Support or Funding InformationUM DearbornThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Conversion of Invasive Species, Rhamnus carthartica, into Combustible Biofuel: A Novel Approach to Conservation
Authors: McCollough Shannon , Eickhoff Isaac , Soneral Paula 
Published: June 2021

Common buckthorn, Rhamnus carthartica, is an invasive species that outcompetes native species throughout North America. Introduced from Europe for horticultural purposes, this decorative shrub is fast‐growing, shade tolerant, and depletes soil nutrients. Given its exquisite fitness and negative consequences to biodiversity, an approach to mitigate the detrimental effects of buckthorn is essential. Can buckthorn biomass be turned into energy? The goal of this project was to evaluate the efficacy and feasibility of transforming buckthorn into combustible ethanol as a long‐term conservation strategy. We asked two central questions in the context of a course‐based undergraduate research experience: 1) Which tissue ‐ leaves, stems, or berries ‐ is the optimal source of biomass? 2) Does pre‐freezing enhance ethanol yield? Tissue harvested from 20 locations in the upper‐midwest were subjected to cellulase pretreatment followed by fermentation. Crude samples were then filtered and subjected to simple and fractional distillation to 95% purity. The ethanol from all sources was combustible. Although berries contained the highest amount of pre‐cellulase glucose, all biomass produced comparable amounts of final ethanol yields (ANOVA p=.93). Freeze‐thaw pretreatment of these tissues produced significantly lower ethanol yields (T‐test p=.00063). Based on this data, we propose a scalable, sustainable, and economically viable buckthorn‐to‐biofuel conversion program that can be implemented in a variety of community contexts.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 relationship between student's learning motivation and life style in a Japanese medical school
Authors: Sato Maki , Miyata Yasushi , Waseda Katsuhisa , Aoki Ruri , Kwahara Chikako , Ban Nobutaro 
Published: June 2021

Motivation research has studied in educational psychology in past decade (Pintrich, 1993; 2000) in primary, secondary and college education (Vansteenkiste et al., 2005). The motivated strategies for learning questionnaire (MSLQ) is a self‐report instrument designed to assess college students' motivational orientations (Pintrichet al., 1993). MSLQ is based on a general cognitive view of motivation. The studies of learning motivation in medical students were limited.In this study, we examined the relation between learning motivation and lifestyle such as food intake and sleep in medical students. 421 medical students participated in the present study. The questionnaire was all anonymous. The survey included that the learning motivation, daily food intake and sleep pattern. We compared those items and learning motivation.In the results, the frequency of breakfast and consumption of vegetable and milk production were correlated with learning motivation, though the sleep duration was not significantly correlated with learning motivation.In conclusion, the balanced food intake including vegetable and milk production could be important factor for improving learning motivation in students.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Studying Stimulus‐Induced Changes in RNA Dynamics by Mutational Mapping through TimeLapse‐seq
Authors: Kiefer Lea , Schofield Jeremy A , Simon Matthew D 
Published: June 2021

The eukaryotic transcriptome is dynamically regulated through RNA transcription and decay allowing cells to respond to environmental stimuli in a rapid and specific manner. The bromodomain inhibitor JQ1, has been extensively studied in the context of cancer cells, as it blocks the activation of specific sets of oncogenes perturbing RNA population dynamics.1 Recently, JQ1 has additionally been found to repress pathogenic response genes in models of heart failure, however the mechanism of this action remains unclear.2 JQ1 is known to block the BET bromodomain reader proteins involved in chromatin remodeling, affecting the transcription of the target genes. We, therefore, aim to study the effect of JQ1 in heart failure on the transcriptional level. While RNA‐sequencing (RNA‐seq) provides a snapshot of the cellular transcriptome, temporal information is lost as rapid changes in the RNA population remain undetected among the excess of preexisting RNA. To gain insight into the role of JQ1‐induced pathways in cardiomyocytes, we are studying changes in RNA dynamics using TimeLapse‐seq3, recently developed nucleotide recoding chemistry that utilizes metabolic labeling in an enrichment‐free RNA‐seq approach. Through recoding of the hydrogen bonding pattern of the metabolic label, TimeLapse‐seq identifies new transcripts through apparent mutations in the RNA‐seq reads. We will describe progress using TimeLapse‐seq as a strategy to study differently regulated transcripts in disease and to deduce the mechanism of JQ1 in heart failure.Support or Funding InformationThis work was supported by the NIH NIGMS T32GM007223 (J.A.S. and E.E.D); NSF Graduate Research Fellowship (E.E.D); NIH New Innovator Award DP2 HD083992‐01 (M.D.S.), and a Searle scholarship (M.D.S.).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Ventricular activation times in rainbow trout and common carp
Authors: Vaikshnoraite Marina Alvirasovna , Azarov Jan 
Published: June 2021

The specific objective of the present study was to find out the presence or absence of a transmural gradient of ventricular activation times in fish having pyramidal and sac‐like hearts, which in turn have relatively pronounced and negligible amount of the compact type of myocardium, respectively.Experiments were done in rainbow trout (Onchorhynchus mykiss, n=6; body weight 320–510 g) and common carp (Cyprinus carpio, n=6; body weight 900–1300 g) presenting fish species with the pyramidal (pronounced compact layer) and sac‐like (negligible compact layer) heart types. The investigation was carried out in accordance with the Guide for the Care and Use of Laboratory Animals, 8th Edition published by the National Academies Press (US) 2011. Body surface ECG was recorded in the longitudinal body axis lead. Ventricular unipolar electrograms were recorded from the ventricular walls as described earlier (Vaykshnorayte et al., 2011). In each ventricular lead, activation time were determined as instants of dV/dt minimum during QRS complex (Coronel et al., 2006). Data are expressed as medians and interquartile intervals. Statistical analysis was performed with SPSS package (IBM SPSS Statistics 23, SPSS, Inc., Chicago, Illinois, USA).Common carps demonstrated significantly longer QRS complex in comparison with rainbow trout (79 (IQR 72–85); 56 (IQR 48–61), P<0.05), whereas a difference in RR interval was statistically insignificant (1892 (IQR 1609–2074); 1470 (IQR 970–2175), P>0.05). The gross activation sequence in both species was similar and demonstrated a direction from atrioventricular junction to apex and anterior base (apicobasal activation gradient, P <0.005). The transmural activation pattern was also similar in the studied animals with the activation spread direction from endocardium to epicardium in all parts of the myocardium (transmural activation gradient, P <0.005). In this way, It implies that a transmural activation pattern do not have differences in hearts with different spongy/compact percentage of the ventricular wall in these fish species.Support or Funding InformationThis work was supported by the Ural Branch of the Russian Academy of Sciences (AAAA‐A18‐ 118012290365‐2) and the Program for Fundamental Research of RAS (AAAA‐A17‐ 117012310154‐6).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Precision Medicine in Psychiatry by Predicting Lithium Treatment Response using Gene Expression Biomarkers and Machine Learning
Authors: Eugene Andy Roger , Eugene Beata , Masiak Jolanta 
Published: June 2021

BackgroundWe tested the hypothesis that transcriptional‐level genes signatures are differentially expressed between male and female bipolar patients, prior to lithium treatment, in a patient cohort who were later were clinically classified as lithium treatment responders using the primary outcome measure of the Clinical Global Impression Scale for Bipolar Disorder‐Severity (CGI‐BP‐S).MethodsGene expression study data was obtained from the Lithium Treatment‐Moderate dose Use Study data accessed from the National Center for Biotechnology Information's Gene Expression Omnibus via accession number GSE4548. Differential gene expression analysis using the CGI‐BP‐S responder status and Gender served as control variables for analysis using the Linear Models for Microarray and RNA‐Seq (limma) package and the Random Forests machine learning algorithm in R for Statistical Computing programming language software.ResultsIn pre‐treatment lithium responders, the following genes were found having a greater than 0.5 fold‐change and differentially expressed indicating a male bias: RBPMS2, SIDT2, CDH23, LILRA5, and KIR2DS5 while the female‐biased genes were identified as: HLA‐H, RPS23, FHL3, RPL10A, NBPF14, PSTPIP2, FAM117B, CHST7, and ABRACL.ConclusionsApplying machine learning methods to gene expression data, we developed a pre‐treatment gender‐specific gene‐expression‐based predictive model selective for lithium treatment responders according to the Clinical Global Impression Scale for Bipolar Disorder‐Severity with an ROC AUC of 0.92 for men and an ROC AUC of 1 for women.Support or Funding InformationNone.