bluuebunny/crossref_metadata_2025 huggingface dataset:
FTSH4 and OMA1 mitochondrial proteases reduce moderate heat stress-induced protein aggregation
Authors: Maziak Agata , Heidorn-Czarna Malgorzata , Weremczuk Aleksandra , Janska Hanna
Published: June 2021

The threat of global warming makes uncovering mechanisms of plant tolerance to long-term moderate heat stress particularly important. We previously reported that Arabidopsis (Arabidopsis thaliana) plants lacking mitochondrial proteases FTSH4 or OMA1 suffer phenotypic changes under long-term stress of 30°C, while their growth at 22°C is not affected. Here we found that these morphological and developmental changes are associated with increased accumulation of insoluble mitochondrial protein aggregates that consist mainly of small heat-shock proteins (sHSPs). Greater accumulation of sHSPs in ftsh4 than oma1 corresponds with more severe phenotypic abnormalities. We showed that the proteolytic activity of FTSH4, and to a lesser extent of OMA1, as well as the chaperone function of FTSH4, is crucial for protecting mitochondrial proteins against aggregation. We demonstrated that HSP23.6 and NADH dehydrogenase subunit 9 present in aggregates are proteolytic substrates of FTSH4, and this form of HSP23.6 is also a substrate of OMA1 protease. In addition, we found that the activity of FTSH4 plays an important role during recovery from elevated to optimal temperatures. Isobaric tags for relative and absolute quantification (iTRAQ)-based proteomic analyses, along with identification of aggregation-prone proteins, implicated mitochondrial pathways affected by protein aggregation (e.g. assembly of complex I) and revealed that the mitochondrial proteomes of ftsh4 and oma1 plants are similarly adapted to long-term moderate heat stress. Overall, our data indicate that both FTSH4 and OMA1 increase the tolerance of plants to long-term moderate heat stress by reducing detergent-tolerant mitochondrial protein aggregation.
Theory-Informed Clinical Practice: How Physical Therapists Can Use Fundamental Interventions to Address Social Determinants of Health
Authors: McCarty Dana , Shanahan Meghan
Published: June 2021

The American Physical Therapy Association’s Vision Statement for the profession is guided by principles of innovation, access, equity, and advocacy, and calls on physical therapists to stretch their influence beyond the walls of the clinic and the individuals they treat. Access and equity are problems that span multiple health care professions and entities; yet, addressing social determinants of health is a paradigm shift that clinicians need continued support to achieve. This article has 2 objectives: (1) to define the Fundamental Cause Theory and the Socioecological Model within the context of physical therapy in order to promote best clinical practice, and (2) to apply the concept of “fundamental interventions” in clinical practice to mitigate the negative impact of downstream effects of social determinants of health across levels of the Socioecological Model—individual, interpersonal, institutional, community, and societal. This theoretical lens provides the conceptual framework necessary for physical therapists to think creatively about ways to change their practice in their own contexts to impact the life of individual patients and transform the movement health of society.

Impact

As health care providers, physical therapists have a responsibility to make every effort to meet the needs of their patients and optimize movement health in society; yet significant structural and systemic barriers often prevent patients from reaching their fullest potential. Clinicians can no longer subscribe to a narrow scope of practice focused on individual attainment of therapy goals. This Perspective discusses Fundamental Cause Theory and the Socioecological Model theoretical frameworks that can help physical therapists develop, test, and implement functional interventions to address the needs of society as a whole.
The Effects of Different Exteroceptive Experiences on the Early Motor Repertoire in Infants With Down Syndrome
Authors: Yardımcı-Lokmanoğlu Bilge Nur , Einspieler Christa , Sırtbaş Gülsen , Porsnok Doğan , Arıkan Zeynep , Livanelioğlu Ayşe , Mutlu Akmer
Published: June 2021

Objective

Down syndrome is a chromosomal abnormality in which muscle tone, motor development, and sensory systems are affected. The objectives of this study were to examine the changes in movements and postures of 3- to 5-month-old infants with Down syndrome and infants who were neurotypical controls during exposure to a rough-textured surface and to compare the differences occurring before and during an exteroceptive condition that was different between the 2 groups.

Methods

In this quasi-experimental study, participants were 20 infants with Down syndrome (8 female infants; age range = 10–18 weeks, mean [SD] = 12 weeks 2 days [2 weeks 2 days]) and 20 age-matched infants with typical development (8 female infants; age range = 9–17 weeks, mean (SD) = 12 weeks 6 days [1 week 5 days]). The movements and postures of the infants, including fidgety movements, were assessed according to the General Movements Assessment, which determines the Motor Optimality Score (MOS), on 2 surfaces.

Results

The MOS outcomes of the infants with Down syndrome (median = 21.5, range = 6–28) were significantly lower than those of the infants who were neurotypical (median = 28, range = 23–28) on a standard mattress. The postures were found to be significantly better in infants with Down syndrome during exposure to a rough-textured surface. The MOS did not change due to the different exteroceptive experiences in infants with Down syndrome and infants who were neurotypical.

Conclusion

The different exteroceptive experiences caused only postural alterations, which might play a crucial role in early intervention programs for infants with Down syndrome.

Impact

This is the first study, to our knowledge, on the effects of different exteroceptive conditions, such as a coco coir mattress covered with muslin fabric, on the early motor repertoire in infants with Down syndrome. The findings showed that infants with Down syndrome had heterogeneity in their fidgety movements and large variability of the MOS, and the MOS results from infants with Down syndrome were lower than those of infants who were neurotypical. Fidgety movements and the MOS did not change due to the different exteroceptive experiences in either group. Significant improvements in posture were observed during exposure to a rough-textured surface. The improvement of posture is essential; clinicians might consider the positive effect of putting an infant with Down syndrome on a rough-textured surface and include this strategy in early intervention programs.
Self-Guided Web-Based Pain Education for People With Musculoskeletal Pain: A Systematic Review and Meta-Analysis
Authors: de Oliveira Lima Lívia , Saragiotto Bruno T , Costa Leonardo Oliveira Pena , Nogueira Leandro Calazans , Meziat-Filho Ney , Reis Felipe J J
Published: June 2021

Objective

The purpose of this study was to investigate the effectiveness of web-based pain education programs without clinical support in patients with musculoskeletal pain.

Methods

PubMed, Scopus, CINAHL, Web of Science, Cochrane Library, and PsycINFO were searched from inception to February 2020. Included studies were randomized clinical trials in which people with musculoskeletal pain were allocated to an experimental group that received web-based pain education as a standalone approach. Three review authors performed data extraction. The PEDro (Physiotherapy Evidence Database) scale was used to assess the methodological quality of the studies. The primary outcomes were pain intensity and disability.

Results

Six trials with a total of 1664 participants were included. There is moderate-quality evidence with a small effect size that web-based pain education programs, as a standalone approach, are better than minimal intervention (no intervention or booklets) for pain intensity (standardized mean difference [SMD] = −0.23; 95% CI = −0.43 to −0.04) in the short term and intermediate term (SMD = −0.26; 95% CI = −0.42 to −0.10). Regarding disability, there is low-quality evidence that web-based pain education programs are better than minimal intervention (SMD = −0.36; 95% CI = −0.64 to −0.07) in the short term. Web-based pain education added to usual care was no better than usual care alone in the intermediate or long term for primary outcomes.

Conclusions

Web-based pain education for adults with musculoskeletal pain, as a standalone approach, was better than minimal intervention for pain intensity and disability in the short term, and for pain intensity in the intermediate term. Web-based pain education added to usual care did not provide additional benefits for primary outcomes in the intermediate or long term.

Impact

Web-based pain education as a standalone intervention provided small improvements in pain intensity and disability in patients with chronic musculoskeletal pain. Poorly resourced settings and overburdened health systems should consider this delivery method in the management of chronic musculoskeletal pain.

Lay Summary

If you have chronic musculoskeletal pain, your physical therapist might recommend web-based pain education as treatment to help you reduce pain intensity and disability.
National Study of Excellence in Pediatric Physical Therapy Education: Design, Methods, and Results
Authors: Moore James G , Birkmeier Marisa C , Lundeen Heather , Dannemiller Lisa , Anderson Deborah K , Furze Jennifer A
Published: June 2021

Objective

The purposes of this study were to identify and describe the attributes of excellence and innovation in professional pediatric physical therapy education and develop a conceptual framework identifying dimensions of excellence.

Methods

A multimethod case study design based on a grounded theory framework was used. Data collection included review of artifacts and field interviews (individual and focus group). A constant-comparative method for within case and across case was used for data analysis to verify and revise coding schemes, identify categories and subcategories, revise emerging themes, and develop a conceptual framework.

Results

Based on results of a predetermined grading rubric, 6 of 17 self-nominated academic sites were selected representing diverse institution types (public/private, Carnegie classification, size) and geographic locations. Pedagogical approaches and method of content delivery varied among programs; all used the essential core competencies. The core pediatric faculty member(s) were Board Certified Clinical Specialists. A conceptual framework was developed based on 4 key dimensions: Culture of Excellence, Exemplary Pediatric Faculty, Pedagogy, and Child and Family as Teacher (CFT), and 16 related elements.

Conclusions

CFT is a unique and nonnegotiable dimension of excellence in pediatric physical therapy education, highlighting the partnership between the learner, child, family, and pediatric faculty member. CFT intersects with the other dimensions and integrates their elements (ie, faculty characteristics, contributions from the child and family, use of instructional strategies) to effectively prepare future pediatric physical therapists. Based on the pervasiveness of this dimension in teaching and learning across all programs, this may be the signature pedagogy of pediatric physical therapy education.

Impact

Results of this study are important to professional physical therapist education administrators, pediatric academic faculty, and clinical educators because they represent an understanding of the attributes of excellence. The model can serve as a guide for best practice in pediatric physical therapy education.
Antifungal Peptides from a Burkholderia Strain Suppress Basal Stem Rot Disease of Oil Palm
Authors: Prihatna Cahya , Pramudito Theodorus Eko , Arifin Arild Ranlym , Nguyen Thi Kim Ngan , Purnamasari Maria Indah , Suwanto Antonius
Published: June 2021

Basal stem rot (BSR) is the most common disease of oil palm (Elaeis guineensis) in Southeast Asia. BSR is caused by a white-rot fungus Ganoderma boninense. The disease is difficult to manage. Therefore, development of novel and environmentally safe approaches to control the disease is important. Species of Burkholderia are known to have diverse lifestyles, some of which can benefit plants by suppressing diseases or increasing plant growth. In the present study, antifungal peptides produced by a bacterial strain isolated from the rhizosphere of an oil palm tree, Burkholderia sp. strain CP01, exhibited strong growth inhibition on G. boninense. A loss-of-function mutant of CP01 was generated, and it has enabled the identification of a 1.2-kDa peptide and its variants as the active antifungal compounds. High-resolution mass spectrometry revealed six analogous compounds with monoisotopic masses similar to the previously reported cyclic lipopeptides occidiofungin and burkholdine. The antifungal compounds of CP01 were secreted into media, and we sought to use CP01 culture extract without living cells to control BSR disease. Glasshouse experiments showed that CP01 culture extract suppressed BSR disease in oil palm seedlings. The ability of CP01 to produce an antifungal substance and suppress plant disease suggests its potential applications as a biofungicide in agriculture.
Functional Morphology of the Dolphin Clitoris
Authors: Orbach Dara N , Brennan Patricia LR
Published: June 2021

Dolphins copulate year‐round despite short estrus periods. Copulation may be pleasurable for female dolphins through clitoral stimulation, as they have large and well‐developed clitorises. Although female mammals possess a clitoris homologous to the penis, the general structure and functional morphology has only been described in a few species. We explore the gross morphology and microanatomy of the common bottlenose dolphin (Tursiops truncatus) clitoris at different developmental stages to assess the potential for erectile tissue to expand during copulation. Excised clitorises were collected opportunistically from eleven post‐mortem dolphins including adults, subadults, and calves. Specimens were subdivided for use in: 1) gross morphology dissections, 2) micro‐computed tomography scans, or 3) paraffin histology and staining (modified Mason's trichrome and hematoxylin and eosin). Erectile tissue was present consistently along the clitoral body that extended from the hood tip to the base. The erectile tissue had a forked shape and similar relative volumes in both the calf and subadult specimens. The erectile tissue was surrounded by a thick layer of smooth muscle along the lateral sides of the crurae, clitoral body, and hood, but not cranially or caudally. Muscle tissue was surrounded by connective tissue. There was a hard bulb with a capsule around it at the root of the clitoris proper that was comprised of dense connective tissue. It appeared to be structural rather than erectile or secretory in nature. Our data provide a baseline for comparisons with other species known to have sex for pleasure (e.g., humans). The consistent shape and relative volumes of erectile tissues between calves and subadults suggest there are few developmental changes except for allometric size increases. Future research that compares the density of connective tissue in cetaceans and other marine and terrestrial mammals may be able to yield insights if the unexpectedly dense tissue of the dolphin clitoris is an adaptation driven by natural selection or sexual selection.

Support or Funding Information

This research was funded by the American Association of Anatomist Short‐term Visiting Scholarship to D.N.O. and a faculty grant from Mount Holyoke College to P.L.R.B.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
How Organic Chemistry Became One of UCLA's Most Popular Classes
Authors: Garg Neil K.
Published: June 2021

Organic chemistry has a bad reputation, despite having a tremendous impact on our everyday lives. It has remained a notorious “weed‐out” class for decades – striking fear in the hearts of students – and has long been viewed as a gatekeeper course for those interested in pursuing a career in medicine. This presentation will examine the underlying teaching philosophies that have now transformed organic chemistry into one of the most popular classes on the UCLA campus. Educational initiatives, including organic chemistry music videos and BACON (Biology And Chemistry Online Notes) tutorials, will be discussed.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Develop of a Neural Network to Evaluate the Cardiovascular Risk Using Body Composition Data
Authors: Zea‐Robles Aura Catalina , Rodriguez‐Arboleda Astrid Yamile , Sáenz Diana Poala , Triana‐Domínguez Freddy Camilo , Leon‐Ariza Henry Humberto
Published: June 2021

Introduction

The cardiovascular disease (CVD) is the main world cause of morbidity and mortality, continually, are searching early diagnostic strategies with enough sensibility and specificity to be used massively in the population. An artificial neural network (ANN) uses mathematical algorithms to predict an event, the vantage of an ANN is the capacity of learning.

Objective

To develop an ANN, to prediction cardiovascular risk using anthropometric variables, age, and habits.

Methods

Was analyzed 256 subjects, aged 16 to 60 years old, the ANN was feed with the variables: age, gender, smoking, fat percentage, visceral fat and muscular percentage, the estimation of body composition was made using bioimpedance, the ANN training was made with 183 subjects (69%), the output variable was the CVD probability to ten years prognosticated using ASSIGN scale, the classification was high risk > 10%, moderate risk 5 – 10%, low risk 1 – 4,9%, very low risk < 1%. The ANN was a multi‐layer perceptron trained with the rest blood pressure, total cholesterol, HDL Cholesterol, LDL Cholesterol, and Triglycerides data; and the familiar antecedents of diabetes, cardiovascular disease, and cerebrovascular disease, the software used was Matlab.

Results

The model show significant differences in the blood chemical variables and the body composition between groups p < 0.0001. The area under the curve for the prediction was: high risk = 0.999, moderate risk = 0.967, low risk = 0.986, very low risk = 0.981. The sensitivity was between 0.750 y 1.000 and specificity was between 0.833 and 1.000.

Conclusion

An ANN that uses like prediction variable the body composition has a high predictive value, besides it is a good tool for the cardiovascular risk estimation and can be used for the screening in different populations. The project wants to evaluate the population during the following 5 years to determinate the real prediction power of the ANN.

Support or Funding Information

The project was funding by the unit of research of the Universidad Santo Tomás, with the support of the department of humanities.

Diagram of the network developed to evaluate cardiovascular risk.

image

Diagram of the network developed to evaluate cardiovascular risk.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Peritoneal regulatory M2 macrophage therapy for ischemic renal injury
Authors: Mao Ruiwen , Wang Chengshi , Liu Shuyun , Zhao Meng , Cui Danli , Zhang Fu ping , Chen Younan , Lu Yanrong , Cheng Jingqiu
Published: June 2021

Objective

Ischemic injury is one of the major causes of acute kidney injury (AKI), and inflammation plays an important role in the ischemic AKI. M2 macrophages had shown antimicrobial and anti‐inflammatory activities, but its effect on AKI has not been reported. This study aims to improve the protection of peritoneal M2 macrophage on renal function in an ischemic AKI model.

Methods

The macrophages (M0) were isolated from peritoneal dialysate of normal mice, and then induced to M2 by IL‐4/IL‐13. Male C57/BL6 mice were randomly divided into three groups: Control, IRI, and IRI+M2. The IRI mice were made by clamping renal pedicles for 30 minutes. After reperfusion, IRI+M2 group mice were injected with M2 macrophage (1×106 cell dissolved in 50 μL PBS) into capsule of kidney. .All mice were scarified at 3 days after surgery, then, the serum creatinine (Scr), blood urea nitrogen (BUN) and uric acid (UA) were measured. Renal pathology was observed by HE and PAS staining. The renal population of M2 /M1 macrophage was analyzed by flow cytometry. Pro‐inflammatory cytokines (IL‐1β/IL‐6/TNF‐α/iNOS) gene expression in kidney of mice were analyzed by real‐time PCR (qPCR).

Results

After 3 days of surgery, IRI mice had increased levels of BUN, Scr and UA compared to control, whereas injected with M2 macrophage significantly reduced BUN, Scr and renal tubular injury score in IRI mice, and the M2/M1 ratio in kidney of IRI+M2 group was significantly higher than IRI mice. In addition, the mRNA levels of inflammatory cytokines (IL‐1β, IL‐6, TNF‐α, and iNOS) in the IRI+M2 mice were significantly lower than those in IRI mice.

Conclusion

These results indicated that peritoneal M2 macrophages could effectively reduce inflammatory response and kidney injury in IRI mice, and thus it may serve as a potential cell therapy for renal diseases.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
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 Information

1R01DK62277, 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 Information

National Institute of Biomedical Imaging and Bioengineering of the National Institute of Health under Award Number T32EB0010216UPP Academic Foundation Award 1R01DK103775

This 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 Information

NIHR21AG054830, MCW Research Affair Committee New Investigator Award

This 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 Information

NIH DC007695

NIH GM103503

NIH GM103412

This 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 Information

National Institute of Justice 85‐IJ‐CX‐0021

This 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 Information

This 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.
Microbial Indole Metabolites Provide a Novel Pathway for Regulation of Intestinal Homeostasis
Authors: Alexeev Erica E. , Kao Daniel J. , Mills Krista B. , Lanis Jordi M. , Lee J. Scott , Dowdell Alexander S. , Schaefer Rachel E.M. , Onyiah Joseph C. , Colgan Sean P.
Published: June 2021

Inflammatory bowel disease (IBD) is a multifactorial chronic condition that result in numerous perturbations in the gastrointestinal mucosa. IBD is characterized by the continual breakdown of the intestinal epithelial barrier leading to an inappropriate immune response towards intestinal microbiota. This exposure promotes inflammation and continued mucosal injury, though the pathogenesis of the disease remains unknown. There is currently significant interest in understanding the role of gut microbiota in IBD. Loss of commensal bacteria and their metabolites may play a role in homeostasis of the intestinal epithelia. Microbes benefit the host through the local synthesis of numerous metabolites. One such metabolite is indole. Indoles are gut microbiota‐derived tryptophan metabolites that are abundant in the healthy mammalian gut and positively influence intestinal health. Using an unbiased metabolomics profiling approach, we identified a selective reduction in microbiota‐derived indole metabolites in active murine colitis. We have developed HPLC‐based technologies to validate these results and quantify indole and indole‐derived metabolites within murine and human colitis samples. We show that exposure of intestinal epithelial cells to indole metabolites induces genes important in formation and maintenance of intestinal barrier. For instance, the anti‐inflammatory cytokine IL‐10 functions through binding to the IL‐10 receptor alpha subunit (IL‐10R1), and colitis is strongly associated with the induction of the epithelial IL‐10R1. Our results have revealed a prominent induction of IL‐10R1 mRNA and protein expression following treatment of intestinal epithelial cells with indole metabolites. We also show a potential role for selective indole metabolites, particularly indole‐3‐propionic acid (IPA), to alleviate disease severity and decrease inflammatory mediators in models of murine colitis. Together, these data suggest that microbial‐derived indoles play a central role in mucosal homeostasis. Based on these findings and ongoing studies, we show that microbial‐derived indole metabolites inhibit inflammation‐induced damage and promote mucosal homeostasis. These studies elucidate a novel role for microbial metabolites in innate immune responses during intestinal inflammation using in vitro and in vivo models. This work will provide new insight and identify possible avenues to utilize indoles as therapeutic approaches for treating IBD.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.