bluuebunny/crossref_metadata_2025_split huggingface dataset:
NFE2L2 synergizes with beta‐catenin gene mutations to induce HCC in patients and mice
Authors: Tao Junyan , Singh Sucha , Liu Silvia , Bell Aaron , Chen Xin , Monga Satdarshan Pal 
Published: June 2021

Nrf/Keap signaling and Wnt/b‐catenin signaling are important in liver pathophysiology. Mutations in NFE2L2 (encoding for Nrf2) and CTNNB1 (encoding for beta‐catenin) can co‐occur in a subset of HCC patients. However, the precise relevance of these co‐occurrences remains obscure. In the current study, we explored the relevance of any cross‐talk between Nrf2 and Wnt signaling using the sleeping beauty transposon/transposase and hydrodynamic tail vein injection (HDTVI) to co‐express relevant mutant forms of CTNNB1 and NFE2L2 in murine livers. TCGA data showed that among the 377 HCC patients, there were 99 patients with CTNNB1 mutation, 15 patients with NFE2L2 mutation and 18 with mutations in KEAP1. 12 patients of the 377 cases had concomitant mutations in CTNNB1 and NFE2L2 or KEAP1, representing around 3% of all and 12% of CTNNB1 mutated cases. We next co‐expressed beta‐catenin‐T41A and NFE2L2‐WT or NFE2LE‐G3A1 or NFE2L2‐T80K in mouse livers, either individually or together. The NFE2L2‐WT:beta‐catenin‐T41A injected mice showed normal gross morphology and histology by H&E test at 14‐weeks post injection. At this time, NFE2L2‐T80K:beta‐catenin‐T41A and NFE2L2‐G31A:beta‐catenin‐T41A groups develop HCC. HCC developed faster in the NFE2L2‐G31A:beta‐catenin‐T41A group versus the NFE2L2‐T80K:beta‐catenin‐T41A group. Several downstream target genes of Nrf2 were up‐regulated significantly in HCCs occurring in these models, including NAD(P)H dehydrogenase [quinone]1 (NQO1) and peroxiredoxin 1 (PRDX1), suggesting the mutations in NFE2L2 to be GOF. There was also an increase in activation of AKT, mTOR and ERK. Likewise, beta‐catenin targets such as GS were increased remarkably. Thus, we have a generated a highly relevant mouse model of HCC representing a subset of human HCC which is characterized by activation of both Nrf2 and Wnt signaling and hence will lend itself well for investigating biology and precision therapies.Support or Funding Information1R01DK62277, 1R01DK100287,1R01CA204586 and Endowed Chair for Experimental Pathology (S.P.M.).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Treatment of a Mouse Model of Cholestasis with a Thyromimetic Improves Biliary Injury But Exacerbates Hepatocyte Injury
Authors: Kosar Karis P , Nejak‐Bowen Kari 
Published: June 2021

Chronic cholestasis results from bile secretory defects or impairment of bile flow, and there are few effective medical therapies available. Thyroid hormone T3 and synthetic thyroid hormone receptor agonists are known to cause induction of hepatocyte proliferation during liver regeneration. However, whether these drugs have therapeutic benefits in cholestatic liver disease is unknown. In this study, we administered GC‐1, a thyromimetic that preferentially acts through the TRb receptor found predominantly in liver, to Mdr2 knockout (KO) mice, which is a commonly used model of sclerosing cholangitis characterized by bile acid (BA) regurgitation, periductular inflammation, and fibrosis. We determined Mdr2 KO mice fed 5mg/kg GC‐1 diet had decreased bilirubin, liver to body weight ratios, serum alkaline phosphatase, but increased serum alanine aminotransferase and aspartate aminotransferase compared to KO mice fed normal diet as early as 1 week on diet. Histologically, KO mice on GC‐1 diet had decreased ductular response, less bridging fibrosis, and fewer SOX9 positive hepatocytes compared to KO on normal diet. Although total liver BA were higher in KO mice fed GC‐1 diet for 2 weeks compared to normal diet, they normalized to KO levels at 4 weeks of diet. To elucidate the mechanism of increased BA accumulation and liver injury, we examined expression of BA transporters and detoxification enzymes. KO mice on GC‐1 diet had decreased bilirubin transport and detoxification genes, such as Mrp3, Cyp2b10, and Oatp4, compared to KO mice on normal diet, with the net result being retention of BA in the hepatocyte. Affymetrix gene array data also indicates that KO mice on GC‐1 have normalized bile acid synthesis compared to WT expression levels. Thus, GC‐1 reduces cholangiocyte injury during cholestasis by inducing retention of BA in hepatocytes, causing injury to the hepatocytes; this occurs through as‐yet unknown mechanisms that are upstream of BA transporters and biosynthesis enzymes and appears to be b‐catenin independent.Support or Funding InformationNational Institute of Biomedical Imaging and Bioengineering of the National Institute of Health under Award Number T32EB0010216UPP Academic Foundation Award 1R01DK103775This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Role of Endothelial YAP1/TAZ Signaling in Lung Regeneration
Authors: Mammoto Tadanori , Mammoto Akiko 
Published: June 2021

Angiogenesis, the formation of new blood capillaries, plays a key role in organ development, homeostasis and regeneration. We have reported that angiogenesis is stimulated during regenerative lung growth after unilateral pneumonectomy (PNX). In addition to chemical factors, mechanical forces play important roles in endothelial cell (EC) growth and differentiation. It is known that mechanical forces change during regenerative lung growth after PNX. However, the mechanism by which changes in mechanical forces after PNX control angiogenesis during regenerative lung growth remains unclear. The mechanosensitive transcriptional co‐activators, Yes‐associated protein (YAP1) and transcriptional co‐activator with PDZ‐binding motif (TAZ), control angiogenesis. Knockdown of endothelial YAP1 suppresses compensatory lung growth after unilateral PNX in adult mice. Parenchymal deformation due to expansion of the remaining lobes and increases in alveolar microvascular perfusion of the remaining lobes after PNX play key roles in the post‐PNX lung growth. Insertion of silicone prosthesis to replace an excised lobe prevents post‐PNX lung growth and decreases YAP1/TAZ expression. Ligation of one lobar pulmonary artery after PNX stimulates compensatory growth of the remaining non‐occluded lung lobes. To analyze the effects of endothelial YAP1 on angiogenesis and epithelial morphogenesis during regenerative lung growth, we implanted fibrin gel on the mouse lung after PNX and found that knockdown of endothelial YAP1 inhibits angiogenesis and alveolar epithelial cell recruitment into hydrogel implanted on the mouse lung. These results suggest that changes in mechanical forces after PNX contributes to regenerative lung growth through endothelial YAP1/TAZ signaling and modulation of endothelial YAP1/TAZ could be novel interventions for the improvement of the strategies for lung regeneration.Support or Funding InformationNIHR21AG054830, MCW Research Affair Committee New Investigator AwardThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
New Principles for Cell and Circuit Function Revealed by Volume Nanoscale Imaging
Authors: Spirou George , Kersting Matthew , Bayliss Tyler , Razzaq Bayan , Holcomb Paul , Morehead Michael , Spencer Nathan , Ellisman Mark , Manis Paul 
Published: June 2021

Computational properties of neural circuits are determined by the integrative properties and synaptic maps of their cellular elements. This information is challenging to acquire. For example, in the auditory system it is incomplete for even the most studied cell type, the bushy cell (BC). BCs encode temporal fluctuations in sound amplitude, and are important for a range of perceptual abilities including sound localization and communication. Prevailing theory is that one of two subtypes of BCs, called globular BCs, accomplish their task by measuring coincidence of similarly weighted sub‐threshold auditory nerve (AN) inputs using short integration time constants. However, the number and sizes of these inputs are not known, and the synaptic map of dendrites is woefully incomplete. We employed serial blockface scanning electron microscopy (SBEM) of mouse cochlear nucleus to acquire this information. This approach revealed more inputs (mean 7.8, mode 8, range 5–12, n = 15 cells) than estimated using physiological methods (mean 5.1, mode 5, range 4–6, n = 8 cells; Cao and Oertel 2010), and a large range of sizes (35 – 302 μm2), and likely influence on BC activity. We discovered a new dendrite structure, called a hub, which can yield up to 13 branches, and further document frequent and periodic swellings along dendritic processes. We completed the first synaptic map for a BC dendrite system, and revealed that entire branches were non‐innervated. Dendrite branches from the same and adjacent BCs were intertwined, and formed direct membrane contacts. We established a pipeline, using 3D virtual reality software, called syGlass, developed in our laboratory, to skeletonize dendrites and export the structures for compartmental modeling in NEURON. These models permitted activation of AN inputs individually, which revealed that the largest input onto one‐half of cells was supra‐threshold. Therefore BCs do not operate via a simple coincidence model of uniformly weighted sub‐threshold inputs. Dendrites served as a tuned current sink, since their removal rendered even the smallest AN input supra‐threshold. Current work is exploring the presence of electrical contacts at apposition of dendrite membrane, and whether these contacts improve synchrony in activity of BC clusters.Support or Funding InformationNIH DC007695NIH GM103503NIH GM103412This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Title Discoveries from the Forensic Anthropology Data Base: Modern American Skeletal Change & the Case of Amelia Earhart
Authors: Jantz Richard 
Published: June 2021

In the mid‐1980s the University of Tennessee (UT) Anthropology Department began accumulating data from forensic cases that came into our laboratory and others around the country providing the first insight into skeletal changes occurring in the past 150 years. Also in the 1980s the UT Forensic Anthropology Center founded a willed body program to study human decomposition. The donated body program formed the basis for an unprecedented collection of modern American skeletons for skeletal biology research. Thus began the Forensic Anthropology Data base (FDB), which now contains osteometric data from over 4000 individuals, most of them of known age, sex, and ancestry, as well as height, weight, place of birth, place of death, and other premortem biological characteristics of interest (e.g. handedness, pathologies, occupation).The FDB data base has resulted in a number of major developments and discoveries, three of which will be summarized in this presentation:

Documentation of remarkable change in cranial and postcranial morphology in the past 150 years. The cranium has become higher, longer and narrower during this time interval. The skeleton has also become more gracile, and limb bone proportions have changed.
Development of a software package, Fordisc 3.1, that uses the FDB and sophisticated statistical algorithms to estimate sex, ancestry and height from bone measurements. The Fordisc software program has changed the face of forensic anthropology casework since its inception in 1993.
Probable identification of Amelia Earhart by comparing estimates of her bone lengths based on photographs to lengths of bones found on Nikumaroro Island in 1940.
Support or Funding InformationNational Institute of Justice 85‐IJ‐CX‐0021This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Natural selection, adaptive plasticity, and avian malaria
Authors: Bonier Fran , Olson Sarena , Schoepf Ivana , Schoenle Laura 
Published: June 2021

Plastic traits, such as variable behavior and physiology, are front‐line components of adaptive responses to dynamic challenges. For example, plastic responses to parasites and pathogens are essential to both resistance and tolerance of infection; yet, these responses can also be associated with high costs, including immunopathology, loss of homeostasis, and expended resources. Because of these costs and benefits, we expect that natural selection will continue to shape and refine plastic responses to parasites. Understanding the ways that selection is shaping plastic traits could help explain differences among individuals, populations, and species, but adaptive plasticity complicates the application of classical approaches to measuring natural selection. In this talk, I will describe our work aimed at understanding how selection acts on plastic responses to infection in a free‐ranging population of red‐winged blackbirds with a remarkably high prevalence (95%) of haemosporidian parasites (e.g., Plasmodium and Haemoproteus). Overall, our findings point to fitness costs of chronic infection that blackbirds tolerate through induction of adaptive plasticity. Our work illustrates both the benefits and perils of applying classical evolutionary approaches to understanding the adaptive significance of individual variation in plastic traits. More broadly, with an evolutionary perspective in the study of plastic traits involved with resistance and tolerance of infection, we can better appreciate the dynamic nature of host‐parasite interactions.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Using “first patient” autopsy assignments to drive self‐directed learning in a medical student population
Authors: Rae Guenevere 
Published: June 2021

Discussing the pathology found in the gross anatomy laboratory with medical students has been suggested as a way to educationally enhance the learning environment. One way to carry out this type of educational enhancement, is to give an “autopsy” assignment to students, asking them to integrate both gross and histologic tissue data acquired during these dissection activities. At LSUHSC, this type of autopsy assignment has been given for the past six years and have been positively received by medical students. Data from these studies will be presented detailing the common pathologies that can be easily identified from an anatomist's perspective using data from anatomic studies of the heart (n=39), lung (n=97), kidney (n=76), and liver (n=49). The anatomic studies include a gross and microscopic evaluation of pathology and artifacts found by medical students dissecting within the gross anatomy laboratory. Data will also be presented from a multi‐year study (n−397) investigating how such autopsy activities in the medical curriculum impact students' diagnostic acumen and their development of clinical reasoning skills. Data will also be presented from the most recent student class (graduating class of 2022; n=199) whose members participated in a year‐long, self‐directed assignment, which included a student group presentation of their autopsy report. A potential framework for meeting LCME standards for self‐directed learning will be discussed, as well as suggestions to assist programs with limited financial and faculty resources.Support or Funding InformationThis project was partially funded by the American Association of Anatomist's Education Research Scholarship.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Painting, Pirouettes and Proving: A Tool‐kit of Methods for Engagement in Anatomy
Authors: Finn Gabrielle M. 
Published: June 2021

Anatomy and art are often synonymous with each other, with celebrated artists such as Leonardo Da Vinci producing not just spectacular art works but, also sharing knowledge through his productions. The public curiosity with anatomy and what lies beneath has not dwindled in the centuries since Da Vinci. Anatomists in medical schools may not perform public dissections as in days gone by, but they are still at the forefront of outreach and public engagement and require a diverse repertoire for such activity.This presentation will discuss the use of a range of modalities for engaging the public and students in living and functional anatomy. Discussion will centre around the use of anatomical body painting and drawing, as well as methods for demonstrating functional anatomy through exercise. Finally, edible organs and the use of baking as a method of learning and demonstrating anatomy will be described. The aim is to share practical wisdom, anecdote, evidence and best practice with fellow anatomists.Examples of the use of body painting within the curriculum, as an outreach activity with school groups and as a tool for recruitment days will be provided. Of course, body painting takes time and for a number of reasons, including cultural barriers, it is not always appropriate. Drawing structures on disposable lab gloves or swimming caps provide another useful alternative – not only is it a quicker activity but the participants also create an artefact that they can take home with them. Working with art and textile specialists can provide another string to the bow, resulting in the creation of wearable anatomies that can be utilised for more complex demonstrations and engagement exercises.Lately, anatomical body painting has evolved to use an even more striking medium, that of Ultra‐Violet (UV) paint. UV provides a wet and therefore more visceral look to paintings, coupled with the vibrant fluorescence. It is visually striking and makes an excellent addition to the toolkit of any anatomy educator. UV paintings are spectacular when used on moving models and exhibited in darkness. The glowing paint on the muscles present as if showing muscle tension. Such painting activities can be used for more functional displays such as our well‐publicised UV yoga and fitness demonstrations. The anatomist and the fitness professional working together can tailor powerful lessons which emphasis the relationship between form and function.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Molecular Genetics for Cryptosporidium
Authors: Striepen Boris 
Published: June 2021

The protozoan parasite Cryptosporidium is a leading cause of severe diarrhea in young children and an important contributor to early childhood mortality. Fully effective drugs and vaccines to treat or prevent cryptosporidiosis are lacking. A main roadblock for their development has the overall poor tractability of this parasite. We established a powerful molecular genetic model to overcome this hurdle. Using this system we can now engineer reporter parasites to derive robust measurements of infection in vitro and in vivo as well asparasite mutants to understand the mechanistic underpinnings of drug sensitivity and resistance in Cryptosporidium. Cryptosporidium is also a fascinating model to understand fundamental parasite biology. How does the parasite's complex sexual lifecycle unfold, and how do parasite, host and commensals interact to shape susceptibility, disease and protection? To address these issues we are pursuing different genetic strategies to identify key factors in the parasite and in the host.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Dissection Dose Response and Laboratory Examination Performance – Influence of Peer Teaching
Authors: Pizzimenti Marc A. 
Published: June 2021

Educational strategies designed to promote student learning and provide opportunities for multiple levels of engagement are important components for curricular design. The current study builds on previous work by comparing the relative amount of dissection participation for unit examinations across two different curricula and how students' perceptions of peer teaching are related. In a previous curriculum, students completed dissections related to 20% or 40% of the content for unit examinations (equal, repeated block design) and were exposed to the remaining content through peer teaching/learning exercises. In the current study, students completed dissections related to 50% of the content for unit examinations and were exposed to the remaining content through peer teaching/learning. Laboratory examination scores increased with increased exposure to dissection (p < .01). Students in the lower quartile of each cohort (LQ) had increased overall score (>7%, p < .01) with the additional dissection experiences, whereas gains for students in the upper quartile (UQ), while significant (p < .01), were lower (< 3.8%). Sub‐scores on questions related to areas in which students completed dissection were higher than scores for questions in which students (initially) learned the material through peer teaching. The perceptions of students about their peers' teaching were similar between the two quartiles on items related to individual depth, and identified limits, of knowledge (p > .05). However, UQ students were rated more highly on organization and being clear when explaining things to others (p < .01). The data suggest that dissection contributes to higher overall laboratory examination scores, particularly for students in the LQ. Learning from peers (over material already dissected) provides an initial exposure for building knowledge, that may be enhanced by the reciprocal exchanges during teaching/learning sessions. While performance on areas that were not dissected by students is generally lower, the pragmatic (and educational) benefits of peer teaching/learning interactions are positive. While dissection and peer teaching would be considered effective strategies in a constructivist learning environment, isolating the exact contribution of each component to a student's knowledge progression remains challenging to discern.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.