bluuebunny/crossref_metadata_2025_split huggingface dataset:
Veterans without mTBI are more likely to benefit from bilateral electrical vestibular stimulation
Authors: Brewer Kelly , Wood Scott , De La Cruz Leslie , Sanjana Faria , Schubert Michael , Serrador Jorge 
Published: June 2021

Damage to the vestibular system is often an unrecognized outcomeof mild Traumatic Brain Injury (mTBI). Ocular torsion can be used as a methodfor determining proper vestibular function of the otoliths with the applicationof imperceptible stochastic noise (SN) used to enhance the otolith‐ocular reflex. The goal of this work was to determine if Veterans with vestibular dysfunction withand without a history of mTBI would show a benefit from imperceptible SN.History of TBI was collected in 122 Veterans (86% male, age 53.7 ± 9.9 years). Thirty‐nine Veteransreported history of mTBI and 76 reported no history. Seven Veterans reported moderateTBI and were excluded from study analysis. History of mTBI was classified as areport of head injury immediately followed by loss of consciousness (less than 30 minutes) or any period of confusion or disorientation. Otolith dysfunctionscreening was performed on 102 Veterans and 41 Veterans returned to participatein repeated testing with and without SN. To assess otolith function andimprovement using imperceptible SN, ocular torsion was collected in response tosinusoidal tilt in the roll plane ± 20 degrees at a frequency of 0.03125 Hz (32sec/cycle). Ocular torsion (OT) gain was used to compare otolith function andimprovement over sham trials using SN.Veterans screened for otolith dysfunction showed similarrates between groups (58% Ctrl vs 57% mTBI). Veterans with no history of mTBIshowed a significant improvement in OCR with SN over those who reported historyof mTBI (mean improvement 21.3±21% Ctrl vs 1.8±19% mTBI, p=0.008). Statistical significance in OCR improvement remainedwhen adjusted for age (p=0.011). While no difference in mean age was observedbetween groups, Veterans with a history of mTBI showed a higher OCR gain withoutSN (0.09 ± 0.04 Ctrl vs 0.12 ± 0.05 mTBI, result not significant).These data show that while Veterans with a history ofmTBI demonstrate similar rates of vestibular impairment in otolith‐ocularreflexes, they may be less likely to benefit as a group from bilateralimperceptible electrical stimulation. Further investigation to clarify vestibular‐mediatedpathways of improvements using imperceptible SN are needed and evaluation of unilateraland canal deficits in adjusting for the use of SN may be a beneficialmodification for those that report a history of mTBI.Support or Funding InformationSupportedby DoD grant W81XWH‐14‐2‐0012This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Transsynaptic Tracing of Sensory‐Motor Connections in the Gut‐Brain Axis
Authors: Parker Coltan G , Grako Megan , Berish Brooks , Dailey Megan J 
Published: June 2021

The neural gut‐brain axis consists of distinct sensory and motor neurons. Sensory neurons innervating the small intestine transmit meal‐related information to the brain, while motor neurons to the small intestine regulate motility and secretion. Previous research has only partially mapped the brain regions directly connected to the gut‐brain axis, and no research has yet investigated sensory‐motor overlap in those brain regions. Here we used transsynaptic viral tracing to identify the brain regions directly connected to the small intestine and quantify the extent of sensory‐motor overlap in those regions. Because transsynaptic tracing has not been done between the brain and small intestine, we needed to first characterize the viral transmission pattern. A motor‐tracing virus (PRV‐152) was injected to the duodenal wall of adult male Sprague‐Dawley (SD) rats (N=4). Viral transmission was allowed for 3, 4, or 5 days. Brains were processed and virus labeled cells were quantified per nucleus. Progressive viral transmission revealed, for the first time, the sequence of brain regions directly connected to the small intestine through the motor gut‐brain axis. Next, we combined PRV‐152 with a sensory tracing virus (H129 #424) in order to identify sensory‐motor overlap. Both viruses were injected to the duodenal wall of adult male SD rats (N=6). Viral transmission was allowed for 5 days. Brains were processed, and single‐ and double‐labeled cells were quantified per nucleus. We found consistent single‐ and double‐labeled populations across brain regions of the gut‐brain axis, suggesting multiple distinct parallel pathways that persist through the axis. This is the first study to reveal the sensory‐motor organization of the gut‐brain axis, and is a step toward phenotyping the neuronal subpopulations involved in gut‐brain axis control. Further work toward generating a phenotypic map of the axis could enable targeted manipulation of specific gut‐brain axis functions.Support or Funding InformationThis work was supported by USDA Hatch (to MJD) ILLU‐538‐926This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The Evolution of Underwater Flight in Manta Rays And Their Relatives (Myliobatidae)
Authors: Hall Kayla C , Hundt Peter , Swenson John , Summers Adam , Crow Karen D 
Published: June 2021

Batoids (skates and stingrays), exhibit swimming modes that can be characterized on a spectrum from undulation (>1 wave present along the fin) to oscillation (<0.5 wave present along the fin). The latter is a derived mode of locomotion that evolved in a group of charismatic batoids that have invaded pelagic environments (family Myliobatidae: manta rays, cownose rays, eagle rays). Oscillatory swimming is associated with changes in pectoral fin morphology, including laterally elongated pectoral fins (wings), a posterior redistribution of pectoral fin rays, and the evolution of modified anterior pectoral fin domains called cephalic lobes‐ anteriorly extended appendages used exclusively for feeding in the Myliobatidae. Variation in the number of fin rays in batoid pectoral fins has not been characterized in a comparative or phylogenetic context. To better understand how the batoid body plan was modified in association with a shift in swimming and feeding modes, we quantified fin rays that articulate with the three primary cartilages of pectoral fins and cephalic lobes in myliobatids and their relatives. We found no evidence that additional anterior fin rays evolved in association with the origin of cephalic lobes. Rather, we found that variation in the distribution of pectoral fin rays is associated with the evolution of the oscillatory swimming mode. Further, the degree of partitioning between the cephalic lobes and pectoral fins may be correlated to species‐specific ecology. We found two distinct variations in body plan morphology and skeletal arrangement in the cephalic lobe and anterior pectoral fins within the genus Myliobatis, which appear to be associated with ecology and habitat. Overall, this research has implications for morphological evolution associated with invasion of the pelagic environment, and the biomechanics of underwater flight.Support or Funding InformationGolden West Women Flyfishers (KCH) and the California State University Council on Ocean Affairs, Science and Technology (KCH), National Science Foundation IOS 1656487 (KDC), and Thematic Collections Network TCN 1701665 (APS).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Clinically relevant congenital reductions in cardiomyocyte N‐glycosylation is sufficient to cause premature death from dilated cardiomyopathy
Authors: Bennett Eric S , Deng Wei , Yip Kay‐Pong , Ednie Andrew R 
Published: June 2021

Dilated cardiomyopathy (DCM) often leads to heart failure and an early death, with upwards of 70% of DCM considered idiopathic. The responsible mechanisms, including for congenital DCM, often are not known. The sequential process of extracellularly facing enzymatic protein glycosylation is altered in human DCM and in individuals with DCM risk factors. However, it is not known whether such altered glycosylation is pathogenic or subsequent to DCM onset, nor are mechanisms understood. The importance of glycosylation is further highlighted by the observation that a significant percentage of patients with congenital disorders of glycosylation present with cardiac deficits including DCM of unknown etiology. Previously we showed that changes in sialic acid levels (typically, the terminal glycan residue) attached to specific voltage‐gated ion channel isoforms (VGIC) impact cardiac electrical signaling through electrostatic mechanisms, with these same changes in protein sialylation also causing stress‐induced HF, further suggesting a link between altered glycosylation and aberrant heart function. However, without availability and use of appropriate models, evidence that links, mechanistically, altered glycosylation to heart disease remains largely circumstantial. Thus, here, we created a cardiomyocyte‐specific knockout strain of a single glycosyltransferase gene (GTKO) whose expression was shown to be altered in human end‐stage idiopathic dilated cardiomyopathy. The GTKO mice present with altered myocyte VGIC gating, action potential waveforms, Ca2+ handling, Ca2+ spark activity and contractility, that together contribute to DCM deteriorating into HF with 100% dying early. The data demonstrate that reductions in N‐glycosylation achieved through cardiomyocyte‐specific deletion of a single glycosyltransferase impacts whole‐heart and myocyte functions, drawing a direct link between changes in myocyte N‐glycosylation and heart disease. Thus, this specific GTKO strain provides the first model to investigate the relationship between glycosylation and cardiac disease, showing that clinically relevant changes in cardiomyocyte complex N‐glycosylation are sufficient to cause dilated cardiomyopathy that deteriorates into heart failure and early death.Support or Funding InformationThis work was supported in part by grants from the National Science Foundation [IOS‐1146882, IOS‐1660926 and CMMI‐1266331; E.S.B.]; an American Heart Association, Greater Southeast Affiliate Grant‐In‐Aid [14GRNT20450148; E.S.B.] and Postdoctoral Fellowship [15POST25710010; A.R.E.]; and a grant from the National Heart, Lung, Blood Institute [1R01HL102171‐03; E.S.B.].This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Mimicking the activation of the ADP‐glucose pyrophosphorylase from Agrobacterium tumefaciens by site directed mutagenesis
Authors: Alghamdi Mashael , Hussien Rania , Patel Hiral , Dobrzynski Emily , Iglesias Alberto , Ballicora Miguel 
Published: June 2021

ADP‐glucose pyrophosphorylase is the enzyme that controls the rate limiting step in the biosynthesis of glycogen and starch in bacteria and plants, respectively. In Agrobacterium tumefaciens, this enzyme is allosterically activated by fructose 6‐phosphate and pyruvate, whereas it is inhibited by AMP. In the crystal structure of the enzyme Ser72 interacts with a sulfate hypothesized to occupy the phosphate of the Fru6P allosteric site. To study the role of this residue, we replaced Ser72 by Ala, Cys, and Trp. In addition, we mutated it to Asp, and Glu to mimic the presence of negative charge of the Fru6P. Replacement by Ala did not significantly change the regulatory properties of the enzyme, indicating that the side chain does not play a critical role. However, we observed that S72D, S72E, S72C, and S72W became insensitive to Fru6P. Cys and Trp residues at position 72 remarkably reduced the specific activity of the enzyme (7.4 and 1.7 U/mg, respectively). On the other hand, S72D and S72E were partially activated (22.3 and 18.9 U/mg, respectively, compared to 8.3 U/mg of the WT). This indicates that the introduction of a carboxylate moiety in position 72 hinders the binding of Fru6P, but partially mimics its presence. These mutants were still activated by pyruvate, which indicates that this region is specifically involved in the activation by Fru6P and not by pyruvate. The mutants were not inhibited AMP inhibitor suggesting that the binding site for Fru6P and inhibitor overlaps. Our results suggest that Ser72 is in the Fru6P regulatory site and, consequently, the sulfate found in the crystal structure must be occupying the site of the phosphate moiety.Support or Funding InformationThis work was supported by NSF Grant MCB 1616851This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The Interplay of Tissue Landscape and Extracellular Signaling during Drosophila Oogenesis
Authors: Starz‐Gaiano Michelle 
Published: June 2021

Extracellular cues control developmental processes in a concentration‐dependent manner. Different amounts of morphogens elicit distinct cell fate decisions, and cells travel up chemoattractant gradients by assessing cue availability. Such signals must be tightly controlled to assure proper function. The concentration of signals in space and time depends on the parameters that govern the signal's release, diffusion, uptake, and decay rates. Chemical cues are often modeled as diffusing into open domains, but the structure of adjacent tissue could influence local signal availability, and thus cellular responses. The relatively simple tissue architecture of the Drosophila egg chamber, in which large germline cells are surrounded by a follicular epithelium, makes an ideal context to study how tissue contours influence extracellular signaling. In mid‐oogenesis, two anterior follicle cells secrete Unpaired (Upd) to activate the conserved factor Signal Transducer and Activator of Transcription (STAT) in nearby cells, and high STAT activity instructs a subset of those cells to become motile. Our genetic analysis identified specific vesicle trafficking components that modulate the secretion rate of Upd. While all cells near the source of Upd are responsive, we found that STAT activation and the resulting arrangements of motile cells often arose in unexpected, asymmetric patterns. We developed a mathematical model of the spatio‐temporal distribution of Upd in three‐dimensions to characterize signaling activity in the extracellular domain. Simulation results and genetic analysis of mutant phenotypes support the idea that irregular tissue domains result in asymmetric distributions of the Upd signal, consistent with outcomes in vivo. Additionally, modeling results suggest that the concentrations of chemoattractant signals that guide the motile cells can be spatially impacted by tissue structure. We conclude that the interstitial space generated by adjacent tissues creates complex distributions of signaling molecules, which impacts responding cells. This work illustrates novel aspects of how tissue topography alters signaling, and sheds light on cell motility during animal development.Support or Funding InformationNational Science Foundation IOS‐1656550This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Breaking new ground: the emergence of non‐canonical functions for telomerase subunits in plants
Authors: Shippen Dorothy 
Published: June 2021

The telomere complex is highly conserved and essential for genome integrity. Recent studies reveal that core constituents of telomerase and the telomere cap can function off the telomere to promote DNA repair and regulate various metabolic processes in the cytoplasm. We are investigating how two telomere‐related factors in Arabidopsis contribute to genome stability through non‐canonical pathways. Protection of telomeres 1 (POT1) encodes a telomere binding protein implicated in chromosome end protection and telomerase regulation. Although most organisms harbor a single POT1 gene, in the few lineages where the POT1 family has expanded the duplicate genes evolved distinct functions. Arabidopsis thaliana provides an extreme example of divergence wherein the POT1a paralog retains the ancestral function of stimulating telomerase activity, while the POT1b paralog localizes to the cytoplasm and plays no direct role in telomere biology. Plants deficient in POT1b are hypersensitive to genotoxic stress as a result of environmental insult or intrinsic metabolic stress, and produce fewer, lower quality seeds. Notably, POT1b transcription is not regulated by genotoxic stress, but instead is developmentally regulated and concentrated in reproductive tissues. These findings indicate that POT1b evolved to serve a protective role for the genome, increasing plant fitness.Arabidopsis also encodes a non‐canonical telomerase‐associated lncRNA called TER2. TER2 is a brand‐new gene unique to A. thaliana. TER2 is induced in response to DNA double‐strand breaks and its induction causes a rapid decrease in telomerase activity, likely to avert inappropriate telomerase action at sites of DNA damage. Unexpectedly, we found that plants doubly deficient in TER2 and POT1a exhibit a highly accelerated rate of telomere shortening that triggers massive genome instability and gross morphological defects earlier than in plants completely lacking telomerase. Thus, TER2 works in concert with the conventional telomerase enzyme to promote genome stability and telomere replication. Strikingly, like POT1b, TER2 can also be found in the cytoplasm and co‐expresses with POT1b in reproductive organs and seeds. As with pot1b mutants, plants lacking TER2 are hypersensitive to genotoxic stress and have reduced fitness. Finally, biochemical experiments indicate that POT1b physically interacts with TER2. Altogether, these data suggest that POT1b and TER2 are co‐evolving a novel protective mechanism for the plant genome.Support or Funding InformationThis research was supported by grants from NIH (R01‐GM065383) and NSF (MCB 1517817) to D.S.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Replication origin licensing deficiency and genome instability during cell cycle re‐entry from quiescence
Authors: Cook Jean , Matson Jacob , House Amy , Perez Joanna 
Published: June 2021

Metazoan cells transition between active cell division cycles and periods of quiescence during development, regeneration, and homeostasis. Prior to cell division, DNA replication initiates during S phase at thousands of origins to ensure timely and complete genome duplication. Each origin that initiates must have been already licensed for replication in the preceding G1 phase by the DNA loading of Minichromosome Maintenance (MCM) complexes. Insufficient origin licensing in G1 causes incomplete replication and is associated with hypersensitivity to replication stress and DNA damage. We hypothesize that physiological differences in G1 length or G1 starting point impact origin licensing dynamics, and that such differences affect genome stability. We have explored origin licensing parameters in the first G1 phase during cell cycle re‐entry from quiescence relative to the G1 phases following mitosis in actively proliferating cells. We used single cell flow cytometry and live cell imaging to define the relationships among cell cycle re‐entry, G1 length, origin licensing dynamics and replication stress in untransformed human epithelial cells. Despite spending a long time in G1 phase, cells re‐entering the cell cycle are significantly underlicensed in the first cell cycle but not the second or subsequent cell cycles. Cells enter their first S phase before licensing is complete and are then hypersensitive to replication stress. Thus, G1 phase upon cell cycle re‐entry is characterized by slow (or delayed) origin licensing and an apparently weak licensing checkpoint. Strikingly, repeated transitions into and out of quiescence and active proliferation exacerbate replication stress and cause hypersensitivity to replication inhibitors Therefore, the transition from quiescence to active division is a particularly sensitive time for genome stability, and the number of transitions into and out of quiescence may play a role in long term cell viability and genome stability.Support or Funding InformationThe UNC Flow Cytometry Core Facility is supported in part by P30 CA016086. This work was supported by a fellowship from the NSF (DGE‐1144081) to J.P.M and by grants from the NIH to J.G.C. (GM083024 and GM102413).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Crowdsourcing the Development of Assessments for Biomolecular Visual Literacy
Authors: Procko Kristen , Bednarski April , Beckham Josh T. , Dean Diane M. , Dries Daniel Robert , Franzen Margaret A. , Jakubowski Henry V. , Novak Walter R. P. , Roberts Rebecca A. , Roca Alberto I. , Terrell Cassidy R. 
Published: June 2021

Biochemistry and molecular biology (BMB) education is rich in images of molecular structures. Yet, as often as we use these images for instruction, we seldom assess whether our students understand choices we make in the images we show (for example, ribbon versus ball‐and‐stick). To that end, the BioMolViz group (BioMolViz.org) is designing instruments and exercises to assess the molecular visual literacy of BMB students. With support from the National Science Foundation, the BioMolViz group partnered with institutions to host regional workshops in which participants wrote and refined more than 180 assessments to address specific learning objectives in the Molecular Visualization Framework. In pre‐ and post‐workshop surveys, participants reported shifts in their approach toward their instruction of molecular visualization literacy in the classroom. Through these workshops, a network of BMB educators collaborated to develop high‐quality assessment instruments, laying the foundation for crowdsourcing molecular visualization assessment development across the BMB education community.Support or Funding InformationThis work was supported by the National Science Foundation under award numbers DUE‐1022793, ‐1323414, ‐1503811 and IUSE‐1712268. Any opinions, findings, and conclusions or recommendations expressed in this publication are those of the authors and do not necessarily reflect the views of the National Science Foundation.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.