bluuebunny/crossref_metadata_2025_split huggingface dataset:
Failed Phenotype Switching by Hepatic Macrophages Produces Persistent Inflammation in Acute Liver Failure
Authors: Strickland Jenna D , Roth Katherine J , Copple Bryan L 
Published: June 2021

Acute liver failure remains a significant health problem with a high rate of mortality. Studies have revealed that acetaminophen‐induced acute liver failure patients with the poorest outcome suffer from a systemic inflammatory response‐like syndrome characterized by excessive production of immunomodulatory cytokines. Unfortunately, the cause of cytokine dysregulation in these patients remains poorly understood. In the present study, we determined whether cytokine dysregulation occurs in mice treated with a dose of acetaminophen that recapitulates many of the features of acute liver failure in patients. Further, we investigated the underlying mechanism. Treatment of mice with a dose of acetaminophen (e.g., 300 mg/kg), normally associated with full liver repair, increased expression of several proinflammatory cytokines, including tumor necrosis factor‐α (TNF‐α). Cytokine levels remained elevated at 48 hours in these mice but returned to baseline by 72 hours. In mice treated with a dose of acetaminophen (e.g., 600 mg/kg) that produces liver injury which fails to repair, cytokine levels were increased out to 48 hours and remained elevated at 72 hours. This indicated a failure to terminate the inflammatory phase of wound healing similar to what occurs in patients. Interestingly, in mice treated with 600 mg/kg acetaminophen, monocyte/macrophages failed to traffic into necrotic lesions and failed to clear dead cell debris by phagocytosis. Studies have suggested that phagocytosis of dead cells terminates cytokine production by proinflammatory monocytes/macrophages. To evaluate this in acetaminophen overdose, proinflammatory monocytes/macrophages were isolated from the livers of mice treated 24 hours earlier with acetaminophen. Exposure of these cells to necrotic hepatocytes increased expression of arginase‐1 and decreased expression of inducible nitric oxide synthase, indicating a switch from an M1‐like proinflammatory macrophage to an M2‐like prorepair macrophage. Further, treatment of these cells with necrotic hepatocytes decreased expression of several proinflammatory cytokines, including TNF‐α. Collectively, these studies suggest that persistent inflammatory cytokine production in some acute liver failure patients may result from a failure of proinflammatory monocytes/macrophages to phagocytose dead cell debris leading to a persistent M1‐like phenotype. Elucidation of the mechanism by which this occurs, could lead to therapies that restore macrophage function and liver repair in acute liver failure patients.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 Intra‐cardiac Neurohumoral Factors in Human Chronic Ischemic Heart Disease
Authors: Shults Nataliia 
Published: June 2021

BackgroundA transient myocardial ischemia results in the destruction of typical metabolic cascades and leaves structural “traces” in the cardiomyocytes and myocardial interstitial components. Those structural “traces” are microscopically determined by disseminated micro‐focal alterations of the ultrastructure of the cardiomyocytes along with increased interstitial fibrosis. However, cardiac sympathetic nerve terminals are more sensitive to transient myocardial ischemia than the cardiomyocytes. The present study performed ultramicroscopic characterizations of sympathetic nerve terminals in human ischemic heart disease.MethodsLeft ventricular myocardial biopsies were taken from patients with chronic ischemic heart disease and examined under transmission electron microscopy (TEM) using the electron‐histochemical method. Ultrastructural details of alterations in cardiac sympathetic nerve terminals were analyzed to assess their role in the fibrosis development and the damage to cardiomyocytes.ResultsIn patients, the decrease in vesicles of sympathetic nerve terminals and the polymorphism of their secretory granules indicate decreased neo‐synthesis of neurotransmitters as well as their up‐take. We also found that glycocalyx is dissociated and micro‐configurated and cell membranes are lysed. These structural observations imply that the neurotransmitter release into the peri‐cellular space activates functions of mast cells, endothelial cells, fibroblasts, contributing to cardiomyocyte damage and the development of myocardial fibrosis.ConclusionThese results suggest that the accumulation of endogenous cardiac neurotransmitters in the myocardial interstitium may lead to the progressive damage to cardiomyocytes and the development of cardiac fibrosis in human ischemic heart disease. Understanding mechanisms of the regulation of endogenous cardiac neurohumoral factors, especially those involved in the initiation, progression and resolution of cardiac fibrosis is crucial to prevent the ventricular cardiomyocyte damage and to design anti‐fibrosis treatment strategies for patients with chronic ischemic heart disease.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Inotropic Agent Digitoxin Strengthens Desmosomal Adhesion in Cardiac Myocytes in an ERK1/2‐dependent Manner
Authors: Schinner Camilla , Olivares‐Florez Silvana , Schlipp Angela , Trenz Sebastian , Feinendegen Manouk , Yeruva Sunil , Waschke Jens 
Published: June 2021

Desmosomal proteins including desmoglein‐2 (DSG2), plakoglobin (PG), and desmoplakin (DP) are components of the intercalated disc and mediate cardiac myocyte cell‐cell adhesion. Enhancement of cardiac myocyte cohesion, referred to as “positive adhesiotropy”, was demonstrated to be a function of sympathetic signaling in the heart and to be relevant for a sufficient positive inotropic response to adrenergic stimulation. Here we used the positive inotropic agent digitoxin to further investigate the link between inotropy and adhesiotropy in cardiac myocytes. Digitoxin failed to enhance cardiac contractility in Langendorff‐perfused mouse hearts lacking the desmosomal plaque protein PG indicating that a positive inotropic response requires intact desmosomal adhesion. To investigate a potential effect of digitoxin on desmosomal adhesion, atomic force microscopy was applied and revealed that digitoxin increased the binding force of the adhesion molecule DSG2 at cell‐cell contact areas. This was paralleled by enhanced cardiac myocyte cohesion in both HL‐1 cardiac myocytes and murine cardiac slices as determined by dissociation assays as well as by accumulation of DSG2, DP and PG at cell‐cell contact areas. However, total protein levels or cytoskeletal anchorage of desmosomal proteins was not affected. siRNA‐mediated depletion of DSG2, PG or DP abrogated increase of cell cohesion demonstrating that intact desmosomal adhesion is required for positive adhesiotropy. Mechanistically, digitoxin caused activation of ERK1/2 but not of p38MAPK or Src. In line with this, inhibition of ERK1/2 signaling using the inhibitor UO 126 abrogated the effects of digitoxin on cell‐cell adhesion and desmosomal reorganization. These results show that the positive inotropic agent digitoxin enhances cardiac myocyte cohesion with reorganization of desmosomal proteins in an ERK1/2‐dependent manner. Desmosomal adhesion seems to be important for a sufficient positive inotropic response of digitoxin treatment which can be medical relevant for the treatment of heart failure.Support or Funding InformationThis work was supported by the Ludwig‐Maximilians‐Universität Munich with the Wifomed program and the Deutsche Forschungsgemeinschaft DFG [grant number WA2474/11‐1 to J.W.]This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Immune Cell Oscillations Drive Circadian Responses in Adaptive Immunity
Authors: Holtkamp Stephan 
Published: June 2021

Under steady state conditions, lymphocyte numbers in blood oscillate with a peak during the behavioral rest phase and a trough during the active phase. Murine T and B cells are rhythmically recruited to the lymph node at the start of the night, regulated by rhythmic in‐phase‐expression of homing mediators (chemokine receptor CCR7 on the lymphocyte and its cognate ligand CCL21 in the lymph node), along with increased adrenergic tone. The co‐ordinated oscillations in the locations of immune cells throughout the day correspond with time‐of‐day variations in adaptive immune responsiveness. We have previously shown differences in the magnitude of immune responses to MOG peptide, H. pylori and influenza A weeks after initial exposure. Here, our further investigations into the early stages of these processes reveal that subcutaneous injection of bone‐marrow derived dendritic cells (BMDCs) leads to a 2‐fold increase in lymph node cellularity after injection during the rest phase (day, ZT7) compared to the active phase (night, ZT19). Using mice with conditional knockout of the circadian gene Bmal1 in T cells, B cells, dendritic cells or myeloid cells, we show that this time‐of‐day effect is dependent upon functional oscillations in each subset. Loss of Bmal1 in any of these populations was sufficient to block the rhythmic response to stimulation. Thus, coordinated oscillations in immune cell networks drive circadian adaptive immune responses.Support or Funding InformationWe are very thankful for our funding agencies: European Research Council (ERC), Deutsche Forschungsgemeinschaft (DFG), Integrated Research Training Group 914 / Sonderforschungsbereich 914 of the Ludwig‐Maximilians‐Universitaet Muenchen, International Max Planck Research School for Life SciencesThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Circadian Control of Leukocyte Numbers in the Circulation
Authors: Hergenhan Sophia Martina 
Published: June 2021

Circadian rhythms play an important role in determining the strength of the immune response. It has previously been shown that leukocyte mobilization from the bone marrow fluctuates over the course of the day. In addition, leukocyte homing to organs contributes to an oscillatory cell count in the circulation. However, it is currently unclear which factors determine oscillations in blood cellularity. Serum transfer experiments with donor serum harvested at different times of the day revealed increased leukocyte numbers in the circulation at specific times. These increases could be blocked by pharmacological targeting of inflammatory cytokines. In addition, germ‐free mice exhibited lower leukocyte counts at specific times and reduced oscillations in overall cellularity. Together, our data point to an important role of inflammatory cytokines in determining oscillatory blood leukocyte counts in the steady state.Support or Funding InformationWe are very thankful for our funding agencies: European Research Council (ERC), Deutsche Forschungsgemeinschaft (DFG), Integrated Research Training Group 914 / Sonderforschungsbereich 914 of the Ludwig‐Maximilians‐Universitaet Muenchen, International Max Planck Research School for Life SciencesThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Therapeutic delivery of ALX‐0171 Nanobody reduces disease severity of human respiratory syncytial virus strain M37 after established RSV infection
Authors: Ackermann Mark , Alnajjar Sarhad , Sitthicharoenchai Panchan , Van Geelen Albert , Gallup Jack M , Stohr Thomas , Brochot Anne , Duprez Linde , Lorios‐Mora Alejandro , Detalle Laurent 
Published: June 2021

Respiratory syncytial virus (RSV) is the most common reason for hospitalization of infants with viral pneumonia but lacks a therapy that is fully satisfactory and effective. ALX‐0171 is a Nanobody directed against RSV F protein that reduces RSV infection and disease severity. In order to determine the optimal dose of therapeutic delivery of ALX‐0171 after RSV infection, three doses of ALX‐0171 (0, 1.4, 2.8 and 11 mg) were delivered by nebulization to lambs at 3, 4, and 5 days after infection with a human strain of RSV (Memphis 37 strain) and assessed for efficacy at 2, 4 and 6 days post infection. Lambs not receiving ALX‐0171 had limited or lacked RSV gross and microscopic lesions, RSV viral antigen in lung and RSV titers at 2 days post RSV but these lesions and viral parameters increased progressively at days 4 and 6. There was a dose‐effect relationship yielding in vivo IC50 and lambs treated with ALX‐0171 lacked lesions 2 days post RSV infection and had reduced lesions and viral parameters at 4 and 6 days post RSV infection compared to lesions in lambs not receiving treatment. These studies determined that ALX‐0171 reduces RSV disease severity when administered after RSV inoculation. Clinically, infants commonly do not receive treatment for RSV until after clinical signs develop and work in this study suggests that ALX‐0171 has potential to reduce RSV disease severity in the face of established RSV infection at optimized doses.Support or Funding InformationThese studies were funded by Ablynx NVThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
3D Printing for the Improvement of Patient Consultation and Consent in Hand Surgery
Authors: Cheung Rocky , Lam Wee 
Published: June 2021

Cadaveric dissection has traditionally been used to educate healthcare professionals about human anatomy, but a multimodal approach is now becoming more prevalent in a modern medical curriculum. The drive for this change is due to limitations in curriculum time and available resources. Anatomy educators have appropriated some technological inventions to alleviate issues posed by dissection. Amongst them, 3D printing technology is one gaining popularity and research interest. It produces physical 3D models from computerised moulds using an addictive fabrication technique. This involves the 3D printing machine interpreting the digital data as a series of cross sections, generated from computer‐aided design software, and laying down successive layers of materials thereby creating a physical model. This study aimed to explore the impact of 3D printed models on clinical consultations in hand surgery and whether they can give more informed consent to patients with hand pathologies. It also documented the manufacturing process of the 3D printed hand models. Prosected cadaveric forearm specimens were scanned by a hand‐held 3D scanner and after post‐processing of the digital data a computerised template was created for printing. The printed models were then painted by a professional artist. The manufacturing process adopted was found to cost less than ones described in other similar studies. Hand clinicians approved of the accuracy, quality as well as the realism of the models and considered they would be helpful in improving patients' understanding of pathologies and treatments. The outcomes of this study provide useful indicators for subsequent studies and patients' feedback and relevant survey would further establish the educational impact of these models.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Exciting New Orleans youth with plastinated anatomic specimens
Authors: Williams Sarah , Rae Guenevere 
Published: June 2021

The purpose of this study was to examine whether the type of anatomy specimen (wet or plastinated) affected the anatomy educational experience of high school students from the New Orleans community. High school educational workshops have been carried out as community outreach activities for many years at Louisiana State University Health Science Center to stimulate area youth's interest in the field of Science. These workshops have traditionally utilized formalin‐fixed wet cadaveric specimens, which necessitated the use of laboratory space and safety materials. For this project, plastinated specimens were prepared and utilized to teach the educational workshops in addition to the wet specimens. After the workshop, the high school students were surveyed on their experience with the organs and also their feelings toward the anatomical sciences. Of the participants that attended these workshops, 49% are underrepresented minorities (African American and/or Latino). Each session was one‐hour in duration, and wet and plastinated specimens were labeled for learning key anatomical features. A total of 108 students were surveyed, with one group (n=46) interacting with both wet and plastinated specimens and a second group (n=62) interacting with only plastinated specimens. Data collected demonstrated that 91% of students learning from both wet and plastinated specimens felt positively toward the field of anatomy and 30% expressed wanting to learn more about anatomy. Of the group learning from only plastinated specimens, 79% reported feeling positively toward the field of anatomy and 20% wanting to learn more about anatomy. These results suggest that plastinated specimens may not significantly decrease student interest in anatomy although when given the choice, the students reported that they preferred the wet specimens. Although plastinated specimens are initially costly, they provide other long‐term benefits. They eliminate formalin exposure for the adolescent participants and also the needs for laboratory storage, gloves and bio‐hazardous waste. Based on the results from this study, we encourage other medical universities to invest in plastinated specimens and incorporate them into community outreach programs to inspire future young anatomists.Support or Funding InformationThis project was funded by the American Association of Anatomists Community Outreach Grant.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Embedding Brains to Educate Minds Inside and Outside the Classroom
Authors: Babcock Katharine Jane , Kong Elizabeth , Zumwalt Ann 
Published: June 2021

Human brains are a powerful tool for teaching neuroscience at all educational levels as their strong emotional salience facilitates a memorable, and thus more effective, learning experience. Unfortunately, these post‐mortem tissues are delicate and typically preserved in chemicals that require handling with gloves in well‐ventilated areas, making their use in educational settings cumbersome. Plastination is a well‐known alternative to this conundrum, however it is expensive, often causes tissue shrinkage, and is still vulnerable to wear and tear. A new technique embedding brain tissue in silicone gel has recently shown great promise as a cost‐effective way to produce specimens that are structurally preserved, safe to handle, and durable for long‐term use. Following a successful pilot project to test the method earlier this year, the Department of Anatomy and Neurobiology's Outreach Committee at the Boston University School of Medicine is currently working to create a permanent collection of normal and pathological silicone‐embedded brain specimens. These will be used in several ways, from supplementing neuroanatomy lessons in medical and graduate school courses, to providing brain demonstrations at different outreach events in the community. Graduate students in our program currently give brain demonstrations at the Museum of Science, Boston, but the tissues can only be handled by demonstrators due to their fragility. The main objective of this project is to create brain specimens that students can hold and interact with in a way that is safe for both them and the specimens. By doing so, brains that were donated for educational purposes will be made accessible to wider audiences while having their delicate structures protected and thus their educational shelf lives extended.Support or Funding InformationThis project was supported with funds from an American Association of Anatomists Education Outreach grant.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Student Perception vs Reality in Medical School Anatomy Education: From Alabama to New York
Authors: Marquez Samuel , Brooks William S 
Published: June 2021

Curricular change has affected medical school teaching across the country and, in particular, the delivery of anatomical education in integrated systems‐based programs. Medical schools endeavor to deliver anatomy content through the most effective teaching modalities for the expressed goal of providing the foundational knowledge students need to be successful on licensing exams, in clerkships, and in residency. Reducing the number of gross anatomy labs, promoting an interactive learning environment, designing self‐directed learning modules, and fostering team‐based collaborations are but some of the current expectations placed upon anatomy educators. Here we report how two medical schools from Alabama (UAB) and New York (Downstate) approach gross anatomy laboratory education, illustrating and contrasting the range of teaching styles and strategies used in their respective curricula. At UAB, gross anatomy is integrated in organ system modules. During laboratory dissections, faculty rotate their coverage for every lab, and towards the end of each lab, there is a review of structures students should have seen during dissection. Anatomy structures are demonstrated on the best dissected donor using an overhead camera to project to the entire lab. At Downstate, faculty are assigned sections (i.e., 5 tables each) where they remain throughout the Unit (e.g., musculoskeletal). Faculty engage in short, pre‐lab talks with students from their section in preparation for each lab, which fosters a rapport between instructor and student. Faculty seek to identify students in need of academic assistance through these interactions. Based on course evaluations, Downstate students perceived that certain groups were receiving superior instruction compared to other groups, while these negative perceptions have not been noted at UAB. Student's t‐tests, however, revealed no statistical significant difference among the 5 sections at Downstate, contradicting the perceived reality. While student perceptions of their learning provide one subset of data, it should not be the primary assessment of their instruction. Evidence of understanding and of competencies, should include direct measures of learning that address learning objectives, structured faculty evaluations and use of assessment guidelines. While student impression of their anatomical education did not match objective metrics of learning, harmony between perception and reality is the worthwhile goal for which to strive.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.