bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modelling the performance of subterranean rodent mandibles using finite element analysis
Authors: Pierzchjlo Garret , Cox Philip , McIntosh Andrew 
Published: June 2021

Subterranean rodents spend most of their lives underground. As such they have developed efficient ways of excavating soil for burrow formation. Most subterranean rodents dig in one of two ways; chisel‐tooth digging, where enamel covered incisors dig through soil; or scratch digging, where keratin covered claws are used. It is thought that chisel‐tooth digging evolved in order to utilize the resilient enamel covered incisor to dig through harder soils compared to keratin filled claws, which can only dig through softer soils. Chisel‐tooth digging requires a high bite force in concert with a wide gape to achieve optimal removal of soil. A previous study compared the performance of the cranium between chisel‐tooth and scratch digging rodents at different gapes which showed the chisel‐tooth digging rodent cranium maintained higher bite forces at wider gapes. The current study compared the performance of chisel‐tooth and scratch digging mandibles using finite element analysis (FEA). To test this hypothesis, finite element models of the mandible were created and solved at varying gapes. Our results show that at small gapes, the chisel‐tooth and scratch digging mandibles show similar performance parameters. However, as gapes increase the chisel‐tooth digging mandibles outperform the scratch digging mandible. Subterranean rodents have a hard food diet and so it is no surprise that there was little difference in performance at small gapes. However, only chisel‐tooth diggers require a larger gape to excavate hard soils. The results of this study show that the mandibular morphology of chisel‐tooth digging rodents has adapted to meet its functional demands.Support or Funding InformationGill Dilliard Faculty Enrichment Fund ABAC FoundationNatural Environment Research Council, Grant/Award Number: G001952This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Structural and functional changes in human aquaporin (AQP4) and its role in the symptoms of glaucoma
Authors: Ales Ruby , Anderson Teresa , Hueffmeier Sarah 
Published: June 2021

As the human body grows older, the eyes become susceptible to an array of conditions that are detrimental to their ability to perceive the world around them, the most severe being a complete loss of vision. Glaucoma is a disease that involves the gradual build‐up of fluid in the eye, an irreversible condition that puts pressure on the optic nerve and eventually renders the victim blind. The focus of this project is to investigate possible treatments on a molecular level for primary open‐angle glaucoma in its later stages. Human aquaporin‐4 (hAQP4), a protein that serves as a water channel in the cell membrane, was identified as a potential treatment for advanced primary open‐angle glaucoma due to its involvement in the production of the aqueous humor (jelly‐like fluid which gives the eye its shape) and its presence in the optic nerve. The Mahtomedi MSOE Center for BioMolecular Modeling MAPS Team used 3D modeling and printing technology to examine structure‐function relationships of hAQP4 in the optic nerve. hAQP4 is found in the eye along with hAQP1, but hAQP4 stands out for its high water permeability, a characteristic that has been attributed to the function of the side chains of asparagines 213 and 97. In hAQP4, these side chains hydrogen bond with a single water molecule at a time as opposed to several, as occurs within other hAQPs. In this poster, we investigate possible structural changes of hAQP4 that cause a buildup of fluid in the eye and how to reverse the effects. We are also exploring the medical implications of potential inhibitors of hAQP4. Being able to activate and deactivate hAQP4 has the potential to allow doctors to drain the fluid buildup in the eye and reverse the effects of glaucoma. Currently, several potential inhibitors of hAQP4 are being investigated, but none have been confirmed.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Determining Accuracy of oAb as a Mechanistic Biomarker for Alzheimer's Disease in Human Plasma
Authors: Faulk Naomi , Valencia‐Olvera Ana , Collins Nicole , LaDu Mary Jo 
Published: June 2021

Alzheimer's disease (AD) is a fatal neurodegenerative disease that is the 6th leading cause of death in the United States with no cure and few palliative treatments. Currently, there is no preventative treatment, and even if such a therapeutic could be identified, without a predictive biomarker, a target population for treatment could not be determined. Although the mechanism remains unclear, AD is caused by increased levels of the amyloid‐b peptide (Ab), which aggregates to form both amyloid plaques and soluble oligomeric Ab (oAb), the latter considered a proximal neurotoxin. We believe that levels of oAb in human plasma are a prognostic biomarker, and have developed and licensed a method for their detection (LOD <5pMol). While age is the greatest risk factor for AD, APOE4 is the greatest genetic risk factor, increasing risk up to 15‐fold compared to the more common APOE3. Importantly, female (♀) APOE4 carriers have an increased risk for AD compared to male (♂) APOE4 carriers. Key to the success of this project has been the stratification of both control and AD subjects by sex within APOE genotype, with the results that plasma oAb levels are: ♀APOE4> ♂APOE4> ♀APOE3> ♂APOE3. This response was observed in two large human post‐mortem cohorts. However, stratification, the principle of personalized medicine, is simply not applied to AD populations. We now seek to threshold oAb levels using longitudinal and human AD trial data to establish prognostic potential, with the goal of partnering with the private sector for commercialization.Support or Funding InformationLaDu lab funding includes an Anonymous Donor, the University of Illinois College of Medicine, and UIC Honors College Grant.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The effects of sex and APOE genotype on the gut microbiome in EFAD transgenic mice
Authors: Maldonado Juan E. , Parikh Ishita J. , Naqib Ankur , Green Stephan J. , Estus Steven , LaDu Mary Jo 
Published: June 2021

While the gut microbiome (GM), the collective genome of bacteria in the gastrointestinal tract, is primarily studied in metabolism and immune defense, the GM may also serve as a diagnostic tool and therapeutic target in neurological disorders, including Alzheimer's disease (AD). While age is the greatest risk factor for AD, the e4allele of APOE is the greatest genetic risk factor, increasing risk up to 15‐fold compared to APOE3, the common genotype. APOE4 is associated with the accelerated accumulation of the peptide amyloid‐b(Ab), which can aggregate to form both amyloid plaques and small soluble aggregates or oligomeric Ab (oAb), the latter considered a proximal neurotoxin. Importantly, among APOE4 carriers, females have an increased AD risk, rate of cognitive loss and accumulation of Ab42 compared to males. Although the GM of individuals with AD exhibit specific microbial differences compared to healthy controls, a greater understanding of how age, APOE genotype and sex contribute to the altered GM in AD may help determine the diagnostic potential of the GM composition. To study the interactions among these AD risk factors, we developed the EFAD‐transgenic mice, which express the human APOE genotypes and over‐express human Ab42. Thus, our hypothesis is that APOE genotype and sex interact to modulate the GM composition in EFAD mice. Fecal samples from 4 month (M) ♂ and ♀ E3FAD and E4FAD mice were sequenced and compared. The Shannon H index, a measure of species richness and diversity, identified a negative correlation between diversity and severity of AD pathology in the 4M EFAD cohorts of mice: ♂E4FAD > ♀E4FAD and ♀E3FAD > ♀E4FAD. Analysis of similarities (ANOSIM) demonstrated significant differences in the GM in E3FAD vs E4FAD across different taxonomic levels (operational taxonomic unit/OTU, Genus, and Family). Comparison across sex within APOE genotype revealed a significant difference between ♂E3FAD vs ♂E4FAD and ♀E3FAD vs ♀E4FAD at all taxonomic levels. Additionally, there is a significant effect for ♂E4FAD vs ♀E4FAD, though only at the OTU level. Further, heatmap analysis demonstrates clustering of ♀E4FAD samples based on 29 OTUs. Therefore, the synergistic effect of APOE4 and female sex on AD risk is exhibited by the GM, observed by the stratification of the EFAD cohorts. This study is the first step in defining the composition of the GM as a function APOE genotype and sex modulation of AD pathology.Support or Funding InformationLaDu lab funding includes institutional funds from the University of Illinois College of Medicine, the Bridge to the Doctorate Fellowship, and the Honor's College Undergraduate Research Award at the University of Illinois at Chicago.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Glycyrrhizinate Dipotassium (DPG) Effects over Skin Wound Healing
Authors: Rocha Thalita , Leite Camila Silva , Tenis Danielle Gatti , Ziegler Jussara , Priolli Denise Golçalves 
Published: June 2021

Skin wound healing is a complex process involving cellular, and molecular events: inflammatory, proliferative, and remodeling phases. Infectious disease, pre‐existing diseases, medications, and aging can negatively interfere in healing. Research on leptin, collagenase, and tretinoin have been done attempting to promote healing. Glycyrrhizinate Dipotassium (DPG), derived from licorice, has anti‐allergic, antibiotic, and anti‐inflammatory effects, besides promoting the skeletal muscle regeneration by activating quiescent satellite cells, leading myoblasts and myotubes differentiation, and forming new muscle fibers. Considering these aspects, we purpose to verify the 2% DPG pharmacological effect on secondary intention wound healing in adult and aged animals. Twenty male Wistar rats were used. Two skins' excisions (2 cm diameter) of normal skin were made in the animal dorsal region (Naïve group). Topical application of 2% DPG was done on the distal wound daily for 7 days (Treated group). The proximal wound was not treated (Control group). After 14 or 21 days (n = 5 each) of wound creation, the samples were excised, fixed in 10% formol, and processed for paraffin inclusion. Slides were stained with hematoxylin and eosin (H&E), and Masson's trichrome (MT) for histological analysis. Wound healing areas, epidermal and dermal measurements were performed. Statistical analysis adopted a 5% coefficient for null hypothesis rejection. Histological analysis revealed intact skins for Naïve group. Control and Treated groups presented skin with epidermis and dermis reshaped: all epidermal layers (basale, spinosum, granulosum, lucidum, and corneum stratum), as papillary and reticular dermis. In aged rats, the wound was smaller in treated than in untreated animals, resulting in a larger scar compared with the adult rats. However, when treated wounds were compared, no differences were found between the wound areas in adult and aged rats. After 14 days the epidermis thickness of adult and aged animals treated with DPG was thicker than untreated animals. However, after 21 days, the adult epidermis thickness of animals treated with DPG was thinner than untreated animals. The dermis thickness of adult and aged animals treated or non‐treated with 2% DPG did not differ. On the 21st day, adult and aged complete reepithelialization were found in treated animals. Results indicate that 2% DPG significantly reverses wounds process to a skin normal state, even for aged animals, by reepithelization, probably acting during inflammatory and proliferative phases of healing. Such results point DPG as a promissory agent to promote skin healing.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Determination of the DNA binding preference of the SIX transcription factor optix in Heliconius butterflies
Authors: Rivera Anthony Rafael , Rodriguez Jose A 
Published: June 2021

Transcription factors (TFs) are sequence‐specific DNA binding proteins that determine cell state and have been shown to control cell differentiation. Evaluating comprehensive DNA specificity profiles of DNA binding proteins is a nontrivial challenge that hinders our ability to decipher gene regulatory networks. Optix is a homeodomain transcription factor that has been identified as a master regulator of red color patterning in the wings Heliconius butterflies. However, the direct gene targets of optix and its role in final wing coloration remains to be determined. We want to determine the intrinsic DNA‐binding preferences of optix. We have over‐expressed and purified full‐length Heliconius optix and its homeodomain (HD) DNA‐binding domain. We will determine the in vitro DNA‐binding specificity of optix protein of Heliconius erato using Cognate Site Identification by High‐Throughput Systematic evolution of ligands by exponential enrichment (HT‐SELEX). Our results will enable us to bioinformatically predict the genomic targets of optix and decipher its role in wing color patterning and development.Support or Funding InformationThis research is supported by: 1) Research Initiative for Scientific Enhancement (RISE) Grant#: 5R25GM061151‐172) NSF EPSCoR Research Infrastructure grant award 1736026This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Decitabine Treatment Demethylates Vast Majority of High‐Confidence Differentially Methylated Regions in HCT‐116 Colorectal Cancer Cells
Authors: Conrad William H , Anderson Jonathan , Balaram Ariane , Ganev Yoan , Gascoigne Samuel , Gimondo Christina , Palmero Brett , Quraishi Ayesha , Rodriguez Alejandro , Sadat Said Omer , Sandler Anna 
Published: June 2021

Colorectal cancer (CRC) is a common, and often incurable, form of cancer. Gene silencing by CpG island hypermethylation often plays a role in CRC progression. Certain regions of the genome, called high confidence differentially‐methylated regions (DMRs), are consistently hypermethylated across numerous patient samples. In this study, we used bisulfite PCR sequencing to investigate methylation levels at DMRs in the promoter region of CDKN2A, DKK3, EN1, MiR34b, SPG20, and TLX1 in HCT‐116 CRC cells. We observed that for all DMRs except CDKN2A, the demethylating agent decitabine significantly reduced CpG methylation. Using ENCODE project data, we observed that transcriptional activator binding inversely correlates with DNA methylation at all of these sites across diverse cancers and cell types. Our data increase resolution of the methylation status at the above DMRs, show the reversibility of methylation at these sites by decitabine, and the likely role of hypermethylation at these sites in gene silencing. In the future, we plan to test if DMR any specific gene silencing protects HCT116 cells.Support or Funding InformationThis work is supported by the Lake Forest College biochemistry and molecular biology program.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The Role of E4BP4 in Apoptosis of Human Leukemia Cells in Culture
Authors: Mitchell‐Velasquez Erick Lenin , Gomez Danny , Medh Rheem D 
Published: June 2021

Apoptosis is a physiological and genetically controlled process of cell death important for development and cellular homeostasis. Several diseases can be attributed to an imbalance between cellular proliferation and attrition, brought on by inadequate or excessive apoptosis. In cancer, a lack of apoptosis causes excessive accumulation of unwanted cells. Apoptosis is primarily regulated via altered expression of key genes and modulation of signal transduction pathways. Our laboratory focuses on understanding the early apoptosis events triggered by chemotherapeutic agents in cell culture models of leukemia. Previous studies have shown that the E4BP4 (adenovirus E4 binding protein 4) gene in upregulated in correlation with apoptosis. E4BP4 upregulation has been implicated in induction of the pro‐apoptotic BIM protein, a member of the Bcl‐2 family of proteins. In studies presented here, we have utilized CRISPR‐mediated genomic editing technology to knock down E4BP4 expression. Three clones with reduced E4BP4 expression were analyzed for their response to Dexamethasone (Dex), a synthetic glucocorticoid and anti‐leukemic agent. While E4BP4 knockdown did not alter the ability of cells to undergo apoptosis in response to Dex, two of the three clones showed a reduction in the extent of BIM upregulation. Residual E4BP4 expression in our knock down clones may be sufficient to evoke an apoptotic response. Further efforts are underway to understand downstream pathways regulated by E4BP4.Support or Funding InformationThis research is funded by a NIH SCORE SC3 award to RDM (GM081099) and a MARC‐U* STAR scholarship to Erick Mitchell‐Velasquez.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Uncovering DNA binding properties of the GATA4 and TBX5 transcription factor complex
Authors: Rosado‐Rodríguez Emili Patricia , Rodríguez‐Ríos Jessica , Rodríguez‐Martínez José 
Published: June 2021

Transcription factors (TFs) are essential master regulators of gene expression. These DNA binding proteins are fundamental for cellular differentiation during development. Eukaryotic TFs are notorious for not working alone and they often bind DNA as multimeric protein complexes to regulate gene expression. GATA4 and TBX5 are transcription factors that are central components of the gene regulatory network of heart development and function. Recent studies have determined the binding specificity of multiple transcription factors as monomers. However, the DNA‐binding properties of the cooperative complex between GATA4 and TBX5 remain undetermined. Based on this, we want to know the intrinsic DNA binding preferences and the emergent properties that result from the cooperative complex formed by GATA4 and TBX5. We used a cell‐free protein expression system to produce GATA4 and TBX5, and we successfully validated their DNA‐binding activity through an Electrophoretic Mobility Shift Assay (EMSA). Subsequently, we will determine the in vitro DNA‐binding specificity of the GATA4:TBX5 complex using Cognate Site Identification (CSI) by High‐Throughput Systematic Evolution of Ligands by Exponential Enrichment (HT‐SELEX). The findings of this study will help understand the DNA‐recognition rules of the GATA4:TBX5 complex and its potential roles in normal heart development.Support or Funding InformationGrant Acknowledgement: This research is funded by the National Institutes of Health ‐ NIH SC1GM127231 and the Puerto Rico Louis Stokes Alliance for Minority Participation (PR‐LSAMP)‐Undergraduate Fellowship.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Three‐dimensional reconstruction of Prdm family gene expression patterns during mouse development stage by tissue clearing technique
Authors: Woo Jiwon , Kang Haewon , Cho Yong‐Eun 
Published: June 2021

The Prdm family has recently spawned considerable interest as it has been implicated in fundamental aspects of cellular differentiation and exhibits expanding ties to human diseases. Several Prdm family members are deregulated in human diseases, most prominently in solid cancers, where they can act as both tumor suppressors or drivers of oncogenic processes. Some Prdm genes might play an essential role in gene expression were confined to the mammalian central nervous system. We hypothesized that the Prdm gene family may also significantly participate in the development of the mammalian nervous system is required to explore how the gene by the advanced pathological analysis. To assess Prdm family gene expressions patterns at the formation of central nervous system during mouse development stage. The study of the genetic regulation of embryonic development requires the three‐dimensional mapping of gene expression at the high‐resolution microscopic level. We generated transparent mouse embryos by new modified passive tissue clearing technique called mPACT method. Mouse embryos of sequential stage were obtained from three distinct developmental stages, intact embryos was optical transparency to mPACT methods in few days. We reconstructed three‐dimensional expression patterns of Prdm family and blood vessel using transparent mouse embryos. Partial Prdm gene expression was concentrated in the brain and spinal cord regions of each embryo. In this study, we developed embryo‐specific simple clearing method for creating see‐through mouse embryo complete with transparent organ. In addition, our study reconfirmed that some Prdm gene might be a transcriptional regulator for normal neural tissue differentiation during mouse embryonic development using three‐dimensional analysis and transparent embryos.Support or Funding InformationThis work was supported by the Brain Korea 21 PLUS Project for Medical Science, Yonsei University. In addition, this work was supported by a grant from the National Research Foundation of Korea (NRF‐2017R1D1A1B03030315).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
A Large Scale Analysis of the Utilization of Programmed ‐1 Ribosomal Frameshifting as a Recoding Mechanism for the Expression of Human Genes
Authors: Du Zhihua , Zhou Xia , Huang Xiaolan 
Published: June 2021

Programmed ‐1 ribosomal frameshifting (PRF) is a translational recoding mechanism widely used in viruses. Efficient PRF events are typically induced by two cis‐acting mRNA signals: a heptanucleotide slippery sequence and a downstream RNA pseudoknot. In human, only three cases of PRF have been reported, all involving retroviral‐like genes and protein products. To evaluate the extent of PRF utilization in the human genome, we have developed a fast and reliable computational scheme for identifying putative pseudoknot‐dependent PRF events and applied the method to a collection of 43,191 human mRNAs in the NCBI RefSeq database. In addition to the three reported cases, our study identified more than two dozen putative PRF cases for further experimental validation. The genes involved in these cases are genuine cellular genes without a viral origin. Moreover, in more than half of these cases, the frameshift site locates far upstream (>250 nt) from the stop codon of the 0 reading frame, which is nonviral‐like. We also performed bioinformatic sequence analysis on the frameshift protein products for more than a dozen of the putative cases. The results provide various degrees of support to the credibility of the cases, indicating that some of these cases may represent real PRF events in human. The outcomes of these events are the production of novel protein isoforms that may have functional difference from the normal proteins.Support or Funding Information1. SIUC Seed Grant2. NIH FoundationThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.