bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disturbed flow disrupts eNOS and caveolin‐1 expression and colocalization via glycocalyx degradation
Authors: Harding Ian , Mensah Solomon , Ebong Eno 
Published: June 2021

Atherosclerosis is the main cause of cardiovascular diseases such as coronary artery and carotid artery disease and is known to occur in specific, atheroprone areas of the vasculature characterized by disturbed flow patterns. The endothelial glycocalyx, a mechanotransductive carbohydrate layer that lines the endothelium, helps maintain vascular homeostasis through flow‐induced regulation of vasculoprotective molecules such as nitric oxide. Areas of atherosclerosis development have been shown to contain diminished glycocalyx expression; however, it is unclear whether glycocalyx degradation contributes to atherosclerosis or is a result of its progression. Here, we investigated the effects of disturbed flow on glycocalyx‐mediated nitric oxide regulation in rat fat pad endothelial cells, which robustly express glycocalyx components. Using a custom parallel‐plate flow chamber, we found that disturbed flow (DF) patterns characteristic of atheroprone regions of the vasculature decrease glycocalyx coverage and thickness in comparison to uniform flow (UF). This decrease was accompanied by a reduction in endothelial nitric oxide synthase (eNOS) expression. For the first time, we discovered that DF also decreased the expression of caveolin‐1 (cav‐1), a core protein of caveolae microvesicles that assist in eNOS activation. Additionally, fluorescence microscopy also demonstrated decreased cav‐1 membrane and upstream distribution as well as decreased eNOS‐cav‐1 colocalization in areas of disturbed flow. Finally, UF exposure upon enzymatic degradation of heparan sulfate, a major glycocalyx component, resulted in DF‐like expression colocalization of eNOS and cav‐1, implicating the glycocalyx in eNOS and cav‐1 regulation. These findings provide new evidence to the body of information on glycocalyx‐mediated endothelial regulation, which collectively suggests that glycocalyx degradation may contribute to atherosclerosis development.Support or Funding InformationThis study was funded by National Institute of Health Grant K01 HL125499, National Science Foundation Grant DGE 1451070, Northeastern University Provost Start‐up funds, and an Engineering Dean's Fellowship provided by Northeastern 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.
Does normobaric hypoxia sustain altitude acclimatization‐induced improvements in fluid intelligence during reintroduction to altitude?
Authors: Beidleman Beth A. , Sils Ingrid V. , Cymerman Allen , Fulco Charles S. , Staab Janet E. , Muza Stephen R. 
Published: June 2021

This study examined whether normobaric hypoxia (NH)treatment is more efficacious than no treatment for sustaining high altitude (HA)acclimatization‐induced improvements in cognitive function during re‐introduction to altitude (RA) following 12‐day return to sea level (SL). Sixteen SL residents (age=23±6 yrs; mean±SE) participated in tests in the following order: 1) 4 d at SL, 2) 12 d at HA (4300 m), 3) 12 d at SL post HA acclimatization(Post) where each received either NH (n=9; FiO2=0.122) or Sham (n=8; FiO2=0.207)treatment, and 4) 24‐h re‐introduction to 4300 m (RA) in a hypobaric chamber. Cognitive performance was assessed using eight tests from the Automated Neuropsychological Assessment Metrics (ANAM) battery as measured by the number of correct responses per minute after 4 hours at SL, HA1, HA11, and RA. Simple reaction time (SRT) and SRT following cognitive fatigue (SRT2) were used to assess psychomotor performance. Go/no‐go (GNG) was used to assess attention and execution function Code substitution delayed (CDD) and Sternberg‐six letter memory (ST6) were used to assess long‐term memory (one component of crystallized intelligence). Procedural reaction time (PRT), mathematical processing (MTH), and spatial discrimination(SPD) were used to assess fluid intelligence. There were no differences in any measure of cognitive performance between the NH and Sham groups so data were combined. The PRT and MTH, respectively, decreased ~17% from SL (119±3; 34±3) to HA1 (99±5; 28±2) (P<0.05), then increased (P<0.05) at HA11 (114±4; 38±3), and remained unchanged at RA (113±3; 34±3). Similarly, SPD decreased ~14% from SL (44±3) to HA1 (38±1) (P<0.05) then increased (P<0.05)at HA11 (45±3), and remained unchanged at RA (45±3). SRT, SRT2, GNG, CDD, and ST6 were unchanged across any of the test days. These results demonstrate that psychomotor performance (SRT and SRT2), attention/executive function (GNG), and long‐term memory (CDD and ST6) were not impacted by acute or chronic exposure to 4300 m altitude. However, fluid intelligence, reflected in measures of processing speed (PRT), working memory(MTH), and spatial discrimination (SPD), decreased dramatically with acute exposure to 4300 m and improved with HA acclimatization. Moreover, improvements in fluid intelligence induced by HA‐acclimatization were retained during RA after 12 days at SL whether or not NH treatment was utilized. Authors' views not official U.S. Army or DoD policy.Support or Funding InformationUS Army Medical and Materiel CommandThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Experimental Validation of a Respiratory Control Model
Authors: Diekman Casey O. , Thomas Peter J. , Wilson Christopher G. 
Published: June 2021

Diekman et al. [Conf Proc IEEE Eng Med Biol Soc (2012) 2012:6669–72] introduced a model for closed‐loop respiratory control incorporating an explicit conductance‐based model of bursting pacemaker cells driven by hypoxia‐sensitive chemosensory feedback. Numerical solution of the model equations revealed two qualitatively distinct asymptotically stable dynamical behaviors: one analogous to regular breathing (eupnea), and a second analogous to pathologically rapid, shallow breathing (tachypnea). As an experimental test of the Diekman et al. model, we created a hybrid in vitro/in silico circuit. We used Real Time eXperimental Interface (RTXI) dynamic clamp to incorporate a living pacemaker cell recorded in vitro into a numerical simulation of the closed‐loop control model in real time. Here we show that the hybrid circuit can sustain the same bistable behavior as the purely computational model, and we assess the ability of the hybrid circuit to recover from simulated bouts of transient hypoxia.Support or Funding InformationThis work originated as an externally mentored postdoctoral project through the Mathematical Biosciences Institute [National Science Foundation (NSF) Grant DMS‐1440386] and was partially supported by NSF Grants DMS‐1413770 (P. J. Thomas), DMS‐1412877 (C. O. Diekman), and DMS‐155237 (C. O. Diekman).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Z‐band and M‐band Titin Splicing and Regulation by RBM20 in Striated Muscles
Authors: Rexiati Maimaiti , Chen Zhilong , Zhu Chaoqun , Cai Hanfang , Stern Allysa , Mozdziak Paul , Ge Ying , Ford Stephen P. , Nathanielsz Peter W. , Guo Wei 
Published: June 2021

Titin (TTN) has multifunctional roles in sarcomere assembly, mechanosignaling transduction and muscle stiffness. TTN splicing generates variable protein sizes that are associated with its functions. Therefore, understanding TTN splicing is important to develop novel treatment for titin‐based diseases. The I‐band TTN splicing and regulation by RBM20 have been extensively studied. However, the Z‐ and Mband splicing and regulation remain poorly understood. Herein, we aimed to define the Z‐ and M‐band splicing in striated muscles, and also determine whether RBM20 regulates the Z‐ and M‐band splicing. Our data discovered four new Z‐band TTN splicing variants, and one of them dominates in mouse, rat, sheep and human heart. Frog and chicken hearts express only one variant. In skeletal muscles, three new Z repeats were detected, and variant with Zr4–6 skipping dominates in the fast muscles, whereas Zr4 skipping dominates in the slow muscle. No developmental changes were detected in the Z‐band. In the M‐band, two new variants were discovered with alternative 3′ splice site in exon363 (Mex5) and alternative 5′ splice site in intron362. However, only sheep heart expresses two new variants, while other species express only one variant with Mex5+. Skeletal muscles express all three M‐band variants with altered ratios of Mex5+ to Mex5−. Lastly, we revealed that RBM20 does not regulate the Z‐and M‐band splicing in the heart, but does in skeletal muscles. Taken together, we characterized the Z‐ and M‐band splicing and provided the first evidence of the role of RBM20 in the Z‐ and M‐band TTN splicing.Support or Funding InformationThis work was supported by the National Institute of Health/National Institute of General Medical Sciences [NIGMSP20GM103432]; the BGIA from the American Heart Association [16BGIA27790136 to WG]; the USDA National Institute of Food and Agriculture [Hatch project 1009266 to WG]; NICHD 1R01HD070096‐01A1 (SPF and PWN). Ying Ge would like to acknowledge NIH R01 HL109810 and HL096971.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 Role of Introgressive Hybridization in Hypoxia Adaptation of the Tibetan Mastiff
Authors: Signore Anthony , Yang Yingzhong , Storz Jay , Ge Ri‐Li 
Published: June 2021

The role of introgressive hybridization as a source of adaptive genetic variation in animal populations is generally unclear, although recent findings suggest it may be more important than previously anticipated. While there are a number of tools to detect introgression, a major challenge is to experimentally confirm that it has played a role in adaptation by documenting the phenotypic effects of introgressed alleles. Animals native to high‐altitude are excellent models for such experimental studies, as it is often possible to formulate clear a priori hypotheses about the adaptive significance of particular changes in phenotype (for example, increases or decreases in the oxygen affinity of hemoglobin [Hb]). There is evidence to suggest that the high‐altitude adaptation of the Tibetan mastiff is, in part, the result of adaptive introgresssion with the Tibetan wolf. One of the introgressed regions between the Tibetan wolf and mastiff spans the entire β‐Hb gene cluster and the upstream cis‐regulatory elements. This has resulted in two non‐synonymous amino acid substitutions in the Tibetan mastiff, with respect to domestic dogs, in each of the adult expressed β‐type globin genes. To assess the functional effects of these mutations, we have measured the Hb‐O2 affinity of Tibetan wolves, Tibetan mastiffs and domestic dogs. These analyses revealed that the high‐altitude canids have Hb‐O2 affinity that is increased relative to domestic dogs (Figure 1). Thus, introgressive hybridization with the Tibetan wolf has resulted in a phenotypic change to the Tibetan mastiff that increases blood‐O2 saturation under hypoxia.Support or Funding InformationThis work is supported by the National Institutes of Health, the National Science foundation, and the Chinese Academy of Sciences.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Quantitative Method Development and Validation of Naloxone and 6α‐naloxol from Male African Green Monkey Plasma.
Authors: Bandaru Veera Venkata Ratnam , Vignola Justin N , Litvin Samantha R , Packer Amber M , Rizkallah Amy S , Orsini David A , Young Sheena A , Soni Sunil D , diTargiani Robert C , Pennington M Ross , Capacio Benedict R 
Published: June 2021

Theopioid epidemic is a rapidly growing crisis around the world. Current models forpharmacokinetic assessment of countermeasures use African green monkeys (AGM). Arapid, sensitive and selective method was developed and validated usingLC‐MS/MS for the determination of naloxone and 6α‐naloxol in AGM plasma. Samplepreparation involved a simple solid phase extraction (SPE) using ahydrophilic‐lipophilic‐balanced reversed‐phase cartridge. Separation of naloxoneand 6α‐naloxol was achieved on a Halo C18, 2.1 × 50 mm, 2.7μ analytical columnusing an Agilent 1290 Infinity HPLC. A solvent system of methanol‐water‐formicacid was used for the elution of analytes. The analytes were detected and monitoredby a SCIEX QTRAP 6500+ triple quadrupole tandem mass spectrometer operatedin electrospray ionization (ESI) positive mode and multiple reaction monitoring(MRM). Molecular ion transitions for naloxone, 6α‐naloxol and naloxone‐D5 were 328.0/212.0,330.0/185.0, and 333.1/212.0 m/z, respectively. The method was validated usingcalibration and recovery assays with spiked samples. Linear calibration curveswere generated over the range of 1.5–100 ng/ml with values for the coefficientof determination (R2) of >0.9950. The values for both inter‐dayand intra‐day precision and accuracy were well within the generally acceptedcriteria for analytical methods (≤15%). This method was subsequentlyused to measure plasma concentrations of naloxone and 6α‐naloxol in male AGMs administerednaloxone subcutaneously and intravenously. The developed method demonstratedexcellent recovery, repeatability, accuracy and sensitivity.Support or Funding InformationDISCLAIMERS. The views expressed in this abstractare those of the authors (s) and do not reflect the official policy of theDepartment of Army, Department of Defense, or U. S. Government. This researchwas supported by the Defense Threat Reduction Agency – Joint Science andTechnology office, Medical S&T Division.Thisproject was supported in part by an appointment to the Research ParticipationProgram for the U.S. Army Medical Research and Materiel Command administratedby the Oak Ridge Institute for Science and Education through an agreementbetween the U.S. Army Medical Research and Materiel Command.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Lymphocyte Specific Protein‐1 Suppresses Hepatocarcinogenesis Driven by Mutant β‐catenin and Met Overexpression
Authors: Koral Kelly , Tao Junyan , Bhushan Bharat , Stoops John , Mars Wendy , Monga Satdarshan Pal , Michalopoulos George 
Published: June 2021

Lymphocyte specific protein‐1 is the gene with the most copy number variations in a cohort of human hepatocellular carcinoma cases. Previous studies have demonstrated that LSP‐1 acts as a suppressor of hepatocellular proliferation in both cancer cell lines and during liver regeneration after partial hepatectomy as well as an inhibitor of migration. Additionally, concurrent Met overexpression and mutant β‐catenin expression has been demonstrated in 9–12.5% of human HCC cases. Therefore, in the present study, we evaluated whether LSP1 expression affects hepatocarcinogenesis driven by mutant β‐catenin (S45Y) and hMet overexpression by utilizing the sleeping beauty transposase system with hydrodynamic tail vein injections in LSP‐1 transgenic (TG) and WT C57/Bl6 mouse models. LSP1 TG mice overexpress LSP1 specifically in hepatocytes using the albumin promoter, alpha‐fetal protein enhancer. LSP1 TG mice displayed very little histological changes as well as decreased MAPK activation in comparison to the C57 WT mice, which exhibited macroscopic tumors, large PCNA positive proliferating nodules and increased ERK phosphorylation at 7 weeks post injection. Our results demonstrate that expression of LSP1 suppresses mutant β‐catenin and Met driven HCC and may represent a novel therapeutic option for this subset of HCC.Support or Funding InformationSupported by Department of Defense grant CA160119, the University of Pittsburgh Menten Endowment, and the Cleveland Foundation Morningstar Fund.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Immune trade‐offs shape disease outcomes at individual and population scales
Authors: Ezenwa Vanessa 
Published: June 2021

Most aspects of an animal's life history are subject to trade‐offs, where a beneficial change in one trait is linked to a detrimental change in another. Immune function is no different and trade‐offs between different components of the immune system are well described. Importantly, these trade‐offs may have significant implications for infectious disease outcomes. For example, trade‐offs in immunity may be particularly important during concurrent infection (i.e. co‐infection), if the host immune response to one pathogen negatively affects the response to another. Focusing on trade‐offs between the T helper cell 1 (Th1) and Th2 branches of the immune system, we examined how infection with gastrointestinal worms, which trigger a Th2‐type immune response in the host, affects the immune response to a bacterial pathogen (Mycobacterium bovis, causative agent of bovine tuberculosis) for which a Th1‐type response is required for defense. By integrating experimental and longitudinal studies of a wild population of African buffalo (Syncerus caffer), we show that this well‐known trade‐off in immune function operates on both ecological and evolutionary time scales with repercussions for individual disease severity and population‐level disease dynamics.Support or Funding InformationNational Science Foundation (Award #DEB‐1102493)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Do Student Misconceptions about Mutations Persist throughout College Education?
Authors: Couch Brock , Seipelt‐Thiemann Rebecca , Reid Joshua , Grimes Zachary , Wasendrof Chloe , James Olena , Peters Nick , Boury Nancy 
Published: June 2021

Genetics is a widely discussed topic both within and outside of science. One particular topic in genetics that is readily encountered outside of the science classroom is mutations. Students encounter mutations through several different avenues (e.g., news, comic books, movies) that may not be scientifically correct. This pre‐exposure to genetics concepts has the potential to misinform their ideas before ever enrolling in a genetics course. Because of this misinformation, genetics can be difficult for students because of the inconsistences in complex terminology, abstract concepts, and having to think across multiple scales. In order for instructors to create curricula for students, they first need to understand the misconceptions of genetics students may bring into the classroom. Instructors also need to understand if their practice is allowing students to overcome their misconceptions or if they are persistent throughout the students' education. The aim of this project is to 1) understand students' misconceptions about mutations and 2) determine if these misconceptions persist as student progress through their undergraduate education. A draft mutations concept inventory was used to collect responses from 454 students in introductory and advanced genetics courses, as well as introductory biology and advanced microbiology courses. The multiple choice questions included a correct answer and distractors from known misconceptions. Utilizing non‐metric dimensional scaling, data was visualized to determine which misconceptions persisted across different courses and which were resolved or created. Further studies aim to more fully explore conceptual understanding and specific misconception types by student group and so that instructors can provide resources that will enable students to gain an accurate conceptual understanding of mutations within genetics, microbiology, and molecular biology.Support or Funding InformationNSF Award #1710262This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
SPOP Regulates the Nuclear Pore Protein NupJ
Authors: Ong Joseph , Torres Jorge Z 
Published: June 2021

Cell processes like growth and division are tightly regulated. One such mechanism of regulation is ubiquitination. Ubiquitination can change a protein's localization or activity, or it can mark the protein for degradation by the ubiquitin proteasome system. The final step of ubiquitination, the transfer of ubiquitin to the target protein, is mediated by E3 ubiquitin ligases and their substrate adaptors, proteins that allow E3 ligases to be selective in choosing their targets. Understanding the targets of E3 ligases and substrate adaptors, then, is crucial to understanding cell regulation and disease mechanisms linked to misregulation of protein levels and activity. SPOP is a Cul3 E3 ubiquitin ligase substrate adaptor whose targets, such as c‐Myc, PD‐L1, and ERG, are crucial for cell cycle progression and cancer proliferation. Through a mass spectrometry screen, we identified SPOP as a potential regulator of NupJ, a nuclear pore protein. Nuclear pore proteins play canonical roles in transport across the nuclear envelope and emerging roles in nuclear envelope morphology and cell division. SPOP and NupJ both co‐localize at the nuclear envelope via immunofluorescence microscopy, and co‐immunoprecipitation experiments demonstrate that SPOP and NupJ bind to each other in vitro and from cell lysates. Similar to overexpression of NupJ, siRNA against SPOP leads to an increase in the number of nuclear envelope defects. Moreoever, overexpressed NupJ leads to defects in cell division. Our results suggest that SPOP regulates NupJ activity and perhaps protein stability of NupJ.Support or Funding InformationJYO is supported by Edwin W. Pauley Fellowship, NSF Graduate Research Fellowship DGE‐1650604, and Ruth L. Kirschstein National Research Service Award GM007185. This work was funded by NSF MCB1243645 (to JZT).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Investigation of structural factors controlling loop dynamics in acyl protein thioesterases
Authors: Johnson R. Jeremy , Hossain Asif 
Published: June 2021

FTT258 is a close bacterial relative of human acyl protein thioesterases (APTs). Human APTs catalyze the depalmitoylation of key signaling proteins attached to the plasma membrane. For FTT258, catalysis was hypothesized to be regulated by the large‐scale movement of an essential dynamic loop, which transitioned the protein between active and inactive states. However, the causes for the movement of this loop are unknown. Herein, we investigated factors that trigger loop movement in APTs like FTT258. In particular, FTT258 was exposed to inhibitors structurally similar to long chain lipids and to membrane‐mimicking surfactants to determine if these factors induce loop movement. Loop movement was detected by measuring the change in intrinsic tryptophan fluorescence of a central tryptophan on the dynamic loop before and after exposure to these conditions. Although inhibitors and substrate mimics induced minor changes in loop dynamics, larger shifts were measured with various membrane‐mimicking surfactants, suggesting that APT loop dynamics are mainly regulated by proximity to the plasma membrane. Ultimately, understanding the factors controlling APT function could provide novel mechanisms for controlling cell signaling.Support or Funding InformationFunded by NSF MCB‐1812971This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.