bluuebunny/crossref_metadata_2025_split huggingface dataset:
Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) Mutations: a Potential Common Cause of Alzheimer's Disease and Musculoskeletal Disorders
Authors: Plotkin Lilian I. 
Published: June 2021

Alzheimer's disease (AD), a worldwide growing health issue, is a purely neurodegenerative form of age‐induced dementia. Interestingly, weight loss is frequently associated with disease severity and clinical progression and has been shown to begin at least ten years before the diagnosis of the disease. Bone frailty and sarcopenia have each also been linked to the onset of this disease, although very little is known about the pathogenesis of these conditions in subjects with AD. Indeed, although a common link between dementia and osteoporosis has been suggested, it has never been conclusively demonstrated. The prevalence of both conditions increase with aging, and some genetic conditions can lead to both AD and osteoporosis. Examples for the potential common cause of the 2 conditions are mutations of the Triggering Receptor Expressed on Myeloid cells 2 (TREM2) gene, primarily expressed in myeloid cells or microglia in brain and in osteoclasts in bone, which result in AD and dementia, as well as in bone fragility. In a recent Genome Wide Association Study, a single nucleotide polymorphism (SNP) encoding the R47H variant in TREM2 was linked with strong single allele genetic risk factors for AD, as well as with increased risk for Parkinson's disease, amyotrophic lateral sclerosis and frontotemporal dementia. In addition, recent studies showed that mice expressing the R47H TREM2 variant exhibit loss of TREM2 function and neuritic dystrophy. In a similar manner, another TREM2 mutation, the Y38C variant, was previously described in the pathogenesis of Nasu‐Hakola disease (also known as PLOSL) which is characterized by extensive white matter loss and frontotemporal‐like dementia and polycystic lipomembranous osteodysplasia. To investigate whether mutations in the TREM2 gene, previously associated with AD and frontotemporal dementia, also affect the skeleton, we analyzed the musculoskeletal phenotype of mice in which the Y38C and R47H variants of the TREM2 gene are ubiquitously expressed, generated by Drs. Lamb and Landreth at the Stark Neuroscience Research Institute, Indiana University School of Medicine. Our studies showed decreased bone mass in mice expressing the TREM2 mutants at 6–8 months of age. Interestingly, even though TREM2 expression was absent in skeletal muscle of wild type mice, mice expressing the R47H TREM2 variant exhibit decrease muscle mass. In summary, our results suggest a common cause of cognitive disorders and bone loss, and support an indirect role of TREM2 mutations on the loss of muscle mass, secondary to the altered bone remodeling.Support or Funding InformationNIH/NIAMS R01AR067210ICMH Collaborative Pilot Project AwardThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Irisin Mediates Effects on Bone via αV Integrin Receptors
Authors: Kim Hyeonwoo , Wrann Christiane D. , Jedrychowski Mark , Kitase Yukiko , Nagano Kenichi , Strutzenberg Timothy S. , Bouxsein Mary L. , Griffin Patrick R. , Baron Roland , Rosen Clifford J. , Bonewald Lynda F. , Spiegelman Bruce M. 
Published: June 2021

Exercise is crucial to prevent obesity, diabetes, fatty liver disease, and osteoporosis. These beneficial effects are partially mediated by myokines, hormone‐like molecules produced by skeletal muscle. Irisin is a myokine which is a cleaved product from fibronectin type III domain‐containing protein 5 (FNDC5) and is shed into the intracellular milieu and blood circulation to reach other organs. Particularly irisin has been shown to have beneficial effects in adipose tissues, brain, and bone. However, the skeletal response to exercise is less clear and the receptor for irisin has not been identified. Here we show that irisin binds to proteins of the αV class of integrins and biophysical studies identify interacting surfaces between irisin and αV/β5 integrin. Irisin increases both osteocytic survival and production of sclerostin, a local modulator of bone remodeling. Chemical inhibition of the αV integrins blocks signaling and function by irisin in osteocytes and fat cells. In vivo, injection of recombinant irisin protein increases the expression of sclerostin in osteocyte‐enriched bone as well as the levels of plasma sclerostin, and chemical inhibition of the αV integrins blocks the irisin‐induced effects. Genetic ablation of FNDC5/irisin completely blocks osteocytic osteolysis and bone resorption induced by ovariectomy, preventing bone loss and supporting an important role for irisin in skeletal remodeling. The identification of the irisin receptor and its roles in bone biology should greatly facilitate our understanding of irisin's function in exercise and human health.Support or Funding InformationHyeonwoo (Chad) Kim was supported by a cardiovascular T32 grant (5T32HL007374‐38). Bruce M. Spiegelman was supported by NIH grants (4 R01DK54477‐19, DK61502, B.M.S.) and the JPB Foundation (629803). Lynda F. Bonewald was supported by NIH grant (PO1AG039335). Clifford J. Rosen was supported by NIH grant (NIDDK RC2 092759).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Scoping Review: The Use of Augmented Reality in Medical and Surgical Anatomical Education and Its Assessment Tools
Authors: Lee Angela , McBain Kimberly , Ventura Nicole M , Noël Geoffroy PJC 
Published: June 2021

IntroductionWith the increasing accessibility to new technologies such as virtual reality and augmented reality (AR), a growing number of educators are exploring how to incorporate such advances to their field of study; anatomical education is no exception.AimThe purpose of this study was to identify the different AR modalities used to teach anatomy to students, medical/veterinarian trainees and surgeons via coursework, and/or procedural training. We also examined the qualitative and quantitative assessment tools used to evaluate the performance of various AR technologies in specific teaching settings.MethodsA scoping review of the Web of Science, Pubmed, Embase and Medline was performed. Search terms were variations of 1) augmented reality, 2) medical or anatomical teaching/education/training, and 3) anatomy or radiology or cadaver. Abstracts, full articles, conference presentations, and guidelines published between January 2000–September 12, 2018 were identified and screened as per Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines. Virtual reality was an exclusion criterion. The number of participants, level of training, name of AR modality, aim of the study, setting of the study (anatomy course vs. procedural training), object that was “augmented”, body system studied, type of assessment tools, and relevant findings were extracted from accepted studies.ResultsPreliminary findings suggests that Microsoft Hololens and projection‐based modalities using Microsoft Kinect were the most prevalent modalities. The studies were mainly conducted in the context of an anatomy course, which primarily assessed usability, learner satisfaction and perceived benefits of AR through questionnaires using variations of the Likert scale. Certain studies also incorporated more objective findings such as pre‐ and post‐AR knowledge tests. However, the majority of those studies failed to use validated tests.Discussion/ConclusionThe current literature seems supportive of the use of AR as an adjunctive teaching tool at the very least. However, the evidence is weak given the lack of studies with robust quantitative and qualitative methodology to objectively determine the influence of the integration of AR on anatomical education. Sufficiently powered studies using validated assessment tools must be conducted to better understand the role of AR in anatomical education.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Structure of auditory nerve synapses in normal and in hearing impaired
Authors: Rubio Maria Eualalia 
Published: June 2021

The neurons of the cochlear nuclei in the brainstem are the first central processors of auditory information, and they provide inputs to all the major brainstem and midbrain auditory nuclei. The synaptic connectivity pattern of neural networks in each part of the cochlear nuclear complex is an essential determinant of their role in information processing. The synapse of the auditory nerve on principal neurons in the cochlear nucleus is biophysically and anatomically specialized for the fast conduction of excitatory currents into the auditory pathway. A growing interest in the field is to determine how auditory nerve synapses adapt to fluctuations in the sound environment. In this paper, we will discuss novel findings related to the structural and molecular responses of auditory nerve synapses and enwrapping astrocytes in the normal hearing and in the hearing impaired.Support or Funding InformationNIDCD/NIH: R01DC013048; R56DC013048This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Molecular mechanisms regulating presynaptic neurotransmitter release and their impact on neuronal circuit function
Authors: Young Samuel M 
Published: June 2021

Deciphering the molecular mechanisms that govern neurotransmitter release at the presynaptic terminal is essential for understanding synaptic strength, plasticity, modulation and pathology. Voltage‐gated Ca2+ channels (VGCCs) regulate the magnitude and location of Ca2+ entry into presynaptic terminals of the central nervous system (CNS) and this determines the probability and kinetics of release of neurotransmitter‐filled synaptic vesicles (SVs) which ultimately impact neuronal circuit output and behavior. Located within the presynaptic terminal is the active zone, a dense network of proteins, which are implicated to regulate SV release by controlling VGCC function. However, the molecular mechanisms by which active zone proteins control VGCC density and organization within the presynaptic terminal are unclear. The calyx of Held, a glutamatergic presynaptic terminal in the auditory brainstem utilizes rapid and temporally precise action potential signaling for encoding information. Since it is the sole input to drive post‐synaptic action potential spiking and due to the ability to directly measure presynaptic Ca2+ currents and correlate them to SV release rates, the calyx is an exceptional model for gaining mechanistic insights into the presynaptic regulation of SV release and neuronal circuit output. We are using transgenic mouse models and novel viral vectors to manipulate presynaptic active zone proteins and CaV2 subtypes at the calyx during different developmental stages. In combination with these molecular manipulations, we utilized morphological analysis of VGGC organization in the presynaptic active zone and presynaptic ultrastructure and electrophysiology to determine their impact on synaptic biophysics, transmission and plasticity. Our results have identified key molecules and uncovered molecular mechanisms regulating CaV2 subtype levels, organization and proximity to SVs thereby controlling synaptic transmission and neuronal circuit output.Support or Funding InformationCurrent Research Support: National Institute of Deafness and Communication Disorders (R01 DC014093), the University of Iowa.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Epigenetics and chronic pain
Authors: Stone Laura S 
Published: June 2021

The emerging field of pain epigenetics will be introduced and the potential implications of this new field will be reviewed. Long‐term programming of gene expression is dynamically regulated by chemical modifications to the DNA and histones collectively referred to as epigenetic modifications. Epigenetic changes are responsive to the environment and have long‐lasting biological consequences. For example, early life neglect results in altered DNA methylation in the brain that are associated with maladaptive behavioural patterns in the adult. Evidence of epigenetic dysregulation in pre‐clinical pain models and in individuals with low back pain will be highlighted. Finally, the potential for epigenetics to understand biological mechanisms, to unmask new therapeutic targets and as biomarkers for chronic pain will be discussed.Support or Funding InformationSupported by The Canadian Institutes for Health Research, The Quebec Pain Research Network and the Louise and Alan Edwards 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.
Structural, Functional and Gene Expression Analyses of the Aorta and Carotid Arteries in Newborn Term and Moderately Preterm Lambs
Authors: Black Mary Jane , Lombardo Paul , Nguyen Vivian , Flores Tracey , Sutherland Megan , Nitsos Ilias , Allison Beth , Parkington Helena , Tare Marianne , Harding Richard , De Matteo Robert , Schneider Michal , Polglase Graeme 
Published: June 2021

BackgroundPreterm birth (< 37 weeks of gestation) occurs in approximately 10% of births worldwide; the majority of preterm births are moderately preterm (between 32 and 36 weeks gestation). We hypothesized that when birth occurs before term the major conduit arteries would be structurally and functionally immature and thus ill‐prepared for the hemodynamic transition that necessarily occurs at birth. Utilising a preclinical sheep model, our aims were to compare the structure and function of the thoracic aorta and common carotid arteries of moderately preterm (0.9 of gestation) and term‐born lambs in the immediate period after birth, and to determine whether there was upregulation of vascular injury‐associated genes following moderate preterm birth.MethodsTime‐mated ewes were induced to vaginally deliver lambs either preterm (132 ± 1 days of gestation; n=11 females and n=10 males) or at term (147 ± 1 days of gestation; n=10 females and n=5 males). At 2 days after birth, ultrasound imaging of the proximal ascending aorta, main, right and left pulmonary arteries and right and left common carotid arteries was conducted in anaesthetised lambs. The lambs were then euthanized and segments of the thoracic aorta and left common carotid artery were either snap frozen for later real‐time PCR analyses or immersion‐fixed in 10% buffered formalin for histological quantification of collagen, smooth muscle and elastin within the medial layer.ResultsOverall there were few differences in vascular structure, wall composition and blood flow measurements of large conduit arteries at postnatal day 2 between moderately preterm and term lambs. However, there was a significant decrease in the proportion of collagen within the thoracic aortic wall (predominantly in males; p=0.048), narrowing of the carotid arteries (p=0.004) and a reduction in peak aortic systolic blood flow (p=0.049); all of which have the potential to impact on cardiovascular function if they persist long‐term. In addition, there was significantly increased mRNA expression of the cell adhesion marker P‐selectin in the thoracic aortic wall (p=0.001) and the pro‐inflammatory marker IL‐1β in the left carotid artery (p=0.04) in preterm lambs, suggestive of postnatal vascular injury.ConclusionsThe findings suggest that offspring born moderately preterm may be at increased risk of cardiovascular impairment later in life.Support or Funding InformationThis study was funded by the National Health and Medical Research Council of AustraliaThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Glycobiology of Host‐Microbe Interactions in the Gut
Authors: Juge Nathalie 
Published: June 2021

The gastrointestinal (GI) tract is colonised by trillions of bacteria collectively known as the ‘gut microbiota’ which have a profound impact on human health. Bacterial adhesion is a critical step for colonization of the host. Cell surface proteins (adhesins or lectins) mediate attachment to the host and initiate colonization by interacting with host proteins or glycoconjugates. However, in contrast to pathogens, the molecular basis for adhesion of commensal bacteria or probiotics to the gut remain poorly defined.The mucus layer covering the GI tract is the first point contact between the gut microbiota and the host. There is an emerging paradigm that mucin glycans are key molecular determinants of gut homeostasis by providing binding sites and/or nutrients to the bacteria which have adapted to the mucosal environment.Here we provide structural and functional insights into how gut bacteria adapt to the GI tract by focusing on the adhesion strategies of two inhabitant species of the GI tract, Ruminococcus gnavus1,2 and Lactobacillus reuter,3,4,5. The presentation will discuss relevant mechanistic insights into the nature, structure and function of bacterial adhesins involved in the interaction between these gut symbionts and the host glycoconjugates. Our results showed that adhesion strategy is species‐ and strain‐specific and occurs via specialised mucus‐binding proteins or carbohydrate‐binding modules. Sialic acid, a terminal epitope in intestinal mucins, plays a critical role in mediating bacterial tropism along the GI tract.Exploring the molecular basis of adhesion by resident species of the gut microbiota is important for the design of microbiota‐targeted strategies to restore gut health.Support or Funding InformationThe work was supported by the Biotechnology and Biological Sciences Research Council (BBSRC), under the Institute Strategic Programme Grant for Gut Microbes and Health (BB/R012490/1).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 Ancestry Genes in Asthma Susceptibility
Authors: Ortega Victor 
Published: June 2021

Adverse racial differences exist throughout respiratory diseases, including asthma where African descent minority groups such as African Americans and Puerto Ricans experience greater asthma risk and morbidity compared to European descent Whites. Advances in genomic technologies have advanced the complexity and quantity of genetic data to analyze and interpret in individuals from different racial groups with varying inter‐individual ancestral backgrounds. The vast majority of genomic studies have been performed in European descent Whites, but there has been increasingly diverse studies consisting of different racial and ethnic groups where differences have been demonstrated in asthma risk, severity, and drug response. A “bottleneck” resulted in a collapse of genetic diversity following the first human colonization of Europe during the Upper Paleolithic period and the more recent mixing of African, European, and Native American ancestries. These recent admixture events have resulted in different ethnic groups with varying degrees of genetic diversity, including variability in genetic tagging architectures and the frequency of genetic variants, particularly rare variants which are most frequently found to be unique to individual ancestries. Variability in genetic ancestral background could be associated with variation that has the potential to alter asthma risk, severity, or therapeutic responsiveness to commonly used therapies. Genomic studies have employed both traditional and admixture‐based whole‐genome approaches in minority, ethnically diverse cohorts resulting in the confirmation of genomic discoveries initially only found in Whites while identifying novel genetic determinants of asthma risk and drug response unique to specific ethnic groups. Large consortium‐based sequencing studies utilize next‐generation whole‐genome sequencing in diverse multi‐ethnic cohorts to provide a map of the genomes of different recently admixed populations to guide future genomic studies. Genomic studies in increasingly diverse cohorts provide an opportunity to facilitate discoveries and are a critical step towards precision medicine applicable to all people.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Opportunities and Challenges for Inter‐Professional One Health Education
Authors: Castellot John , Afifi Linda 
Published: June 2021

One Health is an interdisciplinary approach to optimizing health for humans, animals, and the environment at the local, national, and global level. It incorporates expertise from diverse fields—including human and veterinary medicine, environmental and biological sciences, engineering, public health, political science, urban planning, economics, sociology, epidemiology, and statistical modeling—to study and solve important challenges at the intersection of humans, animals, and the environment.While it is quite easy to get buy‐in from the various stakeholders in One Health, there are many barriers to incorporating inter‐professional education in this area. For example, many undergraduate institutions do not have public health, health profession, and engineering schools. Even universities like Tufts, which has these schools, face significant obstacles in integrating One Health into their curricula.Specific suggestions for overcoming these obstacles will be provided, including seed grant initiatives and mini‐symposia, along with a description of a highly successful inter‐professional One Health activity currently ongoing at our institution: a student‐driven, faculty coordinated “Comparative Anatomy Exchange Day”. This activity involves veterinary, medical, dental, physician assistant, and graduate students.The event is hosted at the medical school, which has a newly‐built Gross Anatomy laboratory. Since human anatomy labs have tables sized for humans, it is not possible to accommodate large animal cadavers. Thus, the focus is on a specific organ system such as the GI system. The vet students bring GI systems from large animals, including horses, cows, camelids, etc; smaller animal cadavers such as birds, cats, dogs, pigs, and sheep are also provided. The medical school provides 1–2 previously dissected cadavers that are especially good for illustrating the GI system.The morning session is devoted to students from the various professional schools presenting the GI system of the human and animal species via a series of short, pithy talks. Following lunch, all of the participants head to the Gross Anatomy laboratory where the human and animal cadavers are displayed. Students go from station to station as they wish. A student is in charge of describing the relevant anatomy at each station, with a small number of faculty available for questions.This activity has proven to be highly popular, despite the fact that it is an optional activity offered on a Saturday afternoon in late April—more than 130 students and faculty participated. Creating One Health activities that are fun, educational, and allow students from different professions to interact is a highly effective way to provide inter‐professional education around One Health.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.