bluuebunny/crossref_metadata_2025 huggingface dataset:
C/EBPɑ is crucial determinant of epithelial homeostasis by preventing epithelial‐to‐mesenchymal transition
Authors: Coffer Paul , Lourenco Ana‐Rita , Frederiks Cindy , Seinstra Danielle , Margarido Andreia , Roukens Guy , van Rheenen Jacco
Published: June 2021

Extracellular signals such as transforming growth factor beta (TGF‐β) have been shown to influence both tumor initiation and metastasis. TGF‐β has been demonstrated to induce epithelial‐to‐mesenchymal transition (EMT) in cancers of epithelial origin by promoting molecular and phenotypical changes resulting in pro‐metastatic characteristics. Using global RNA‐sequencing analysis, we identified CCAAT/enhancer binding protein alpha (C/EBPα) as one of most TGF‐β‐mediated downregulated transcription factors in human mammary epithelial cells. Here, we show that upon TGF‐β pathway activation, SMAD3 binding to the CEBPA locus is enriched while SMAD3‐knockdown cells fail to repress CEBPA expression. Constitutive C/EBPα expression impaired TGF‐β‐driven EMT by inhibiting the expression of known EMT factors including N‐cadherin, MMP‐2 or ZEB1, and by maintaining E‐cadherin expression. Conversely, depletion of C/EBPα expression alone was sufficient to induce mesenchymal‐like morphology and molecular features. Moreover, cells that had undergone TGF‐β‐induced EMT reverted to an epithelial‐like state upon C/EBPα re‐expression. TGF‐β‐mediated disruption of epithelial spheroids architecture could also be rescued by the introduction of C/EBPα. By using an established mouse model of breast cancer EMT‐driven metastasis, we show that mice injected with tumor organoids constitutively expressing C/EBPα display a dramatic reduction of metastatic lesions in their lungs compared to controls. Taken together, these results show that C/EBPα is required for maintaining epithelial homeostasis by repressing the expression of key mesenchymal markers, thus preventing EMT‐mediated tumorigenesis. These data suggest that C/EBPα is an epithelial “gatekeeper” whose expression is required to prevent unwarranted mesenchymal transition, thereby supporting an important role for EMT in mediating breast cancer metastasis.

Support or Funding Information

This work was supported by a grant from the Dutch Cancer Foundation (KWF).

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Clinically‐Oriented Verbal Laboratory Assessments in the Gross Anatomy Pre‐Clerkship Medical Curriculum that are Designed to Assess Multiple Competencies
Authors: Martin Charys M.
Published: June 2021

One of the fundamental principles of a competency‐based medical education curriculum is the integration of the assessment with the curriculum. Assessment needs to be designed to drive learning and similarly learning should drive assessment. Canadian medical schools follow the framework outlined by the Royal College of Physicians and Surgeons of Canada that a competent physician embodies the competencies of all seven CanMeds Roles: Medical Expert, Communicator, Collaborator, Leader, Health Advocate, Scholar, and Professional. All assessments within an integrated competency‐based medical education curriculum should assess more than medical expert. As such, at the Schulich School of Medicine and Dentistry at Western University, we re‐structured traditional bell‐ringer exams into verbal assessments with both individual and group components. Our goal in offering verbal assessments in a group setting was threefold: 1) students would be assessed in three CanMeds Roles: medical expert, collaborator, and communicator; 2) students would be able to receive immediate formative feedback on their knowledge level which in turn would promote mastery of the material; and 3) the verbal assessment would allow us to better assess the application of anatomical knowledge within a clinical context. This talk focusses on the effectiveness and limitations of this new model of assessment. In addition, the process and resources required for the in‐laboratory verbal assessments will be outlined and future directions will be explored.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Integrated Self‐Study Medical Histology Modules: Innovative Approach
Authors: Hussein Inaya Hajj
Published: June 2021

For the past seven years, at Oakland University William Beaumont School of Medicine (OUWB), increased emphasis is being placed to implement integrated medical curricula, especially those focusing on students' critical thinking and active participation in a clinically relevant approach. Consequently, the teaching of anatomical sciences, in particular Histology, suffered from a reduction in the teaching hours. In this regard, innovative strategies for teaching and assessment were encouraged to assure reaching the acquired competencies.

Along this line, a histology module for each organ‐system was developed and interactive strategies were designed to promote student‐centered and active learning, teamwork and peer teaching as well as self and peer assessment. Students displayed considerable initiative in exploring the histological features of tissues, identifying the changes in various pathological states and recognizing the relationship to clinical manifestations. Such a well‐structured approach, with students working in small groups, enhanced active participation, critical thinking, and self‐directed learning in a clinical context. Different types of formative assessments were adopted in order to meet the expectations and challenges associated with acquiring the set of competencies in the integrated curricular. The study modules were designed for students to use modern and interactive technology for self and peer assessment. This peer teaching and peer assessment approach helped students identify areas of weakness and deficiencies, thus allowing for timely interventions to adjust and compensate for lacunes and provided a positive environment and a stimulus for improvement.

In this era of periodic revisions of the medical curricula, assessment in a timely manner is getting a considerable importance in orienting such revisions. It is a key feature and a fundamental component to monitor and evaluate, at various levels, the rate of success as well as the direction of amendments to make. In this respect, this renewed approach to self and peer assessment is considered effective in enhancing life‐long learning skills and attitudes. It also can minimize the potential adverse impact of decreasing teaching hours in anatomical sciences, while ensuring that learning remains both meaningful and interesting. However, it takes more efforts from teachers and students.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The Origin Recognition Complex: where it all begins
Authors: Joshua‐Tor Leemor , Tocilj Ante , On Kenneth , Yuan Zuanning , Sun Jingchuan , Li Huilin , Stillman Bruce
Published: June 2021

Binding of the Origin Recognition Complex (ORC) to origins of replication marks the first step in the initiation of replication of the genome in all eukaryotic cells. I will present the structure of the active form of human ORC determined by X‐ray crystallography and cryo‐electron microscopy. The complex is composed of an ORC1/4/5 motor module lobe in an organization reminiscent of the DNA polymerase clamp loader complexes. A second lobe contains the ORC2/3 subunits. The complex is organized as a double‐layered shallow corkscrew, with the AAA+ and AAA+‐like domains forming one layer, and the winged‐helix domains (WHDs) forming a top layer. CDC6 fits easily between ORC1 and ORC2, completing the ring and the DNA‐binding channel, forming an additional ATP hydrolysis site. Analysis of the ATPase activity of the complex provides a basis for understanding ORC activity as well as molecular defects observed in Meier‐Gorlin Syndrome mutations.

Support or Funding Information

Howard Hughes Medical Institute

National Institutes of Health

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Quantifying Two Dimensional (2D) and Three Dimensional (3D) Anatomical Learning Using a Neuroeducational Approach
Authors: Anderson Sarah J. , Jamniczky Heather , Krigolson Olav , Hecker Kent
Published: June 2021

Background

Advances in computer visualization enabling both 2D and 3D representation have generated tools to aid perception of spatial relationships and provide a new forum for instructional design. To date, studies examining the effectiveness of these educational tools have been comparative, using performance measurement as proxy variables for learning. A key knowledge gap in the field of health professional education is the lack of understanding of how the brain processes and learns from spatially presented content.

Objective

To use a reinforcement‐based learning activity to assess learning with 2D and 3D (stereoscopic) anatomical representations by comparing event‐related brain potentials (ERPs) as measured by electroencephalography (EEG).

Methods

Mean ERP waveforms of two ERP components, N250 (related to object perception) and reward positivity (related to learners responding to positive feedback), were compared as novice participants (n = 61) learned to identify and localize neuroanatomical structures. Participants learned from 2D, 3D or a combination of 2D and 3D models.

Results

N250 is significantly greater when participants view 3D versus 2D represented anatomical images. Behavioural learning curves and reward positivity did not differ based on model type used during initial learning. However, interleaved learning incorporating 2D and 3D models provided an advantage in retention and transfer activities represented by decreased reward positivity.

Conclusion

Despite the lack of difference in behavioural‐based learning efficiency outcomes for 2D versus 3D models, neural measures reveal new insights. Greater object recognition was noted for participants learning from 3D models and interleaved training using both 2D and 3D model types provides advantages for memory retention. These new insights should be kept in mind as educators are designing learning activities in the anatomical sciences. Validation of quantitative neurophysiological variables that measure learning will enable a direct measure of knowledge acquisition that can be used to strategically assess and optimize new forms of teaching, learning, and evaluation.

Support or Funding Information

This research was supported by University of Calgary grants (competitive) awarded to the authors including: Teaching and Learning Grant; University Research Grants Committee (URGC) Seed Grant; and the Data and Technology Fund. SA would like to acknowledge scholarship funding provided by: Social Sciences and Humanities Research Council (SSHRC) Doctoral Fellowship; Alberta Innovates Health Solutions (AIHS) Graduate Studentship, and the Queen Elizabeth II Graduate Doctoral Scholarship.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Vinculin in Neutrophil Adhesion, Motility and Trafficking
Authors: Wilson Zachary , Harman Michael , Hazlett Lauren , Odzer Jamie , Witt Hadley , Franck Christian , Reichner Jonathan , Lefort Craig
Published: June 2021

Neutrophils are innate immune effector cells that migrate from the blood to resolve bacterial and fungal infections. Understanding how neutrophils migrate is critical for regulating excessive inflammation and subsequent collateral injury. β2 integrins are essential to classical neutrophil recruitment from the blood, and the activation of β2 integrins has been well defined in previous studies. Adhesion stabilization of neutrophils on the endothelial surface as they crawl into a favorable position for transmigration is not as well defined. Neutrophils do not make mature focal adhesions, but do express the focal adhesion protein vinculin. Vinculin associates with integrins by binding to talin‐1 and stabilizes integrin adhesions by recruiting various actin‐associated proteins or by associating with actin directly. This study characterizes the role of vinculin in neutrophil β2 integrin‐dependent adhesion, motility and anti‐bacterial function. Intrinsic activation of β2 integrins is unaffected by vinculin knockout after CXCL1 activation. Vinculin knockout attenuates neutrophil adhesion, spreading, and motility on glass coated with β2 integrin ligand, ICAM‐1, and activating CXCL1. Vinculin knockout also reduces neutrophil spreading in response to ICAM‐1/CXCL1 on polyacrylamide gels of high stiffness but not lower stiffness. Vinculin knockout reduces traction stresses of neutrophils and the actin stiffening response after stimulation. Unlike static conditions, vinculin knockout does not affect neutrophil motility under flow conditions. Vinculin knockout attenuates respiratory burst, but does not affect phagocytosis. In mixed chimeric mice given intraperitoneal thioglycollate, we find comparable migration of vinculin‐knockout and vinculin‐sufficient neutrophils into the peritoneum. Altogether, while vinculin enhances neutrophil β2 integrin adhesion strength, vinculin knockout does not affect neutrophil motility and trafficking under physiological conditions.

Support or Funding Information

American Heart Association (12SDG12080281), Scientist Development Grant CL

Department of Surgery, Rhode Island Hospital

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
STAT3 signaling mediates FAK inhibitor response and resistance in pancreatic cancer
Authors: Jiang Hong , Knolhoff Brett L. , Krisnawan Varintra , DeNardo David
Published: June 2021

Pancreatic cancer is not responsive to targeted therapy. This may be due to the presence of a uniquely fibrotic and immunosuppressive tumor microenvironment present in pancreatic ductal adenocarcinoma (PDAC). Critical obstacles to targeted therapy in PDAC tumors include the dense desmoplastic stroma that acts as a physical barrier to drug delivery and the high numbers of tumor‐associated immunosuppressive cells. In our previous study, we identified hyperactivated focal adhesion kinase (FAK) activity in neoplastic PDAC cells as a significant regulator of the fibrotic and immunosuppressive tumor microenvironment (TME). FAK inhibition (VS‐4718) significantly limited tumor progression, and prolonged mice survival. Herein, we observed that STAT3 signaling was constantly activated in non‐responsive and recurrent tumors, suggesting STAT3 signaling pathway regulates FAK inhibitor (FAKi) response and resistance. Furthermore, gene enrichment analysis showed that TGF‐b signaling was significantly downregulated upon FAK inhibition, suggesting a negative feed back regulation of STAT3 by TGF‐ b signaling. We proposed that overcoming STAT3 reactivation upon FAK inhibition would enhance pancreatic cancer sensitive to FAK inhibitor. Accordingly, we found that combined STAT3 inhibition (Stattic) with FAK inhibition significantly prolonged the survival in the p48‐Cre/LSL‐KrasG12D/p53Flox/ Flox (KPPC) mouse model of human PDAC. This alteration in tumor progression was associated with dramatically reduced tumor fibrosis, decreased numbers of immunosuppressive myeloid cells and increased tumor cell death. Together, our data indicate that STAT3 inhibition sensitizes PADC to FAKi and overcomes FAKi resistance.

Support or Funding Information

This work was supported by Lustgarten Foundation, an AACR/PANCAN Award, NCI awards R01‐CA177670, R01‐CA203890 and R21‐CA182701

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Non‐enzymatic Functions of Aldolase A Induce Oct4 Activation to Promote Lung Cancer Stemness
Authors: Chang Yu‐Chan , Hsiao Michael
Published: June 2021

ALDOA is involved in glycolysis process. The enzyme can exert its function to catalyze Fructose 1, 6‐bisphosphate to glyceraldehyde 3‐phosphate and dihydroxyacetone phosphate. In recent year, several reports focusing on exploring the non‐enzymatic role of ALDOA to control proliferation and/or enhance metastasis ability in cancer. However, its roles in cancer stemness remain unclear. Therefore, we established the ALDOA‐based transcriptomics and proteomics database to explore its functional roles in lung cancer. Through Genespring software to normalization, we have selected candidate targets for prediction potential upstream regulator and pathway by Ingenuity Pathway Analysis (IPA) that may be mediated the induction of lung cancer stemness. Our preliminary results showed that stemness‐related transcription factor Oct4 was activated in ALDOA overexpressed cell. Furthermore, we designed several specific mutant forms of ALDOA to block its enzymatic activity or wild‐type ALDOA expression. We observed ALDOA still induced significant in vitro sphere formations and in vivo tumorigenicity. Knockdown of these molecules of Oct4 downstream could significantly decrease stemness ability in lung cancer. In addition, the established ALDOA transcriptomics database in our study identified the candidate drug that significantly suppressed Oct4 activation‐induced axis signaling and suppressed ALDOA induced invasion in vitro and metastasis in vivo. Combined All evidences, our study reveals novel ALDOA functional roles in inducing cancer stemness through activating Oct4 transcriptomic responses. These findings provided a new therapeutic strategy to modulate the Oct4 activation and downstream signalling to combat lung cancers stemness.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Role of differential phosphorylation of JAM‐A in regulating epithelial barrier function
Authors: Fan Shuling , Weight Caroline , Hilgarth Roland , Nusrat Asma , Parkos Charles
Published: June 2021

Junctional adhesion molecule‐A (JAM‐A) is an epithelial tight junction protein that has been shown to play an important role in regulating intestinal permeability through association with a scaffold signaling complex containing ZO‐2, Afadin and the small GTPase Rap2. A previous study identified serine phosphorylation of the cytoplasmic tail of JAM‐A (p‐S284) and implicated its role in stabilizing tight junctions in MDCK cells. Here, we report that the cytoplasmic tail of JAM‐A is tyrosine phosphorylated (p‐Y280) under inflammatory conditions associated with loss of barrier. While minimal Y280 phosphorylation was observed in model intestinal epithelial monolayers with assembled intercellular junctions, serine phosphorylation was robust. Conversely, exposure of epithelial cells to cytokines IL‐22 or IL‐17a resulted in time dependent increase in p‐Y280 that paralleled compromised epithelial barrier function assessed by measurement of transepithelial resistance to passive ion flow or paracellular flux of 4kDa dextran. Consistent with these in‐vitro findings, in normal colonic mucosa, there was prominent serine phosphorylation but no tyrosine phosphorylation of JAM‐A. However, the opposite was observed in colonic mucosa of individuals with ulcerative colitis and in mice with experimentally induced colitis (DSS) where serine phosphorylation was lost and tyrosine phosphorylation was robust. Coimmunoprecipitation and knockdown experiments identified a role of Src kinase Yes‐1 in mediating tyrosine phosphorylation of JAM‐A. Consistent with these findings, treatment of epithelial monolayers with the Src kinase inhibitor PP2 was able to partially rescue the barrier defect associated with cytokine exposure and tyrosine phosphorylation of JAM‐A (p‐Y280). Analysis of protein interactions with JAM‐A under conditions of tyrosine phosphorylation revealed loss of tight junction‐associated p‐JAM‐A Y280 and scaffold proteins ZO‐2 and active Rap2 in parallel with compromise in the epithelial barrier function. These results suggest that JAM‐A mediated regulation of intestinal epithelial permeability is dependent on a delicate balance between serine and tyrosine phosphorylation events that are altered during inflammation resulting in a leaky barrier.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Birth Defects of the Craniofacial Skeleton and the Potential for Prevention
Authors: Trainor Paul
Published: June 2021

Craniofacial anomalies account for approximately one‐third of all birth defects, and common anomalies such as cleft palate, craniosynostosis, and mandibulofacial dysostosis can occur in isolation or as part of one of nearly 700 distinct syndromes. Most of the bone, cartilage and connective tissue of the head and face is derived from a stem cell and progenitor cell population called neural crest cells. Congenital craniofacial anomalies are therefore typically associated with defects in neural crest cell development. Understanding the etiology and pathogenesis of craniofacial birth defects is dependent upon knowledge of the mechanisms that govern neural crest cell formation, migration, survival and differentiation. Recently, we discovered that ribosome biogenesis, the process of making ribosomes which are essential for protein translation in all cells, plays an essential role in neural crest cell proliferation and survival during craniofacial development. Ribosome biogenesis commences with transcription of rDNA by RNA Polymerases I and III, and this event is considered a rate‐limiting step in ribosome biogenesis. Mutations in genes that encode subunits of RNA Polymerase I, or its associated factors, lead to deficiencies in ribosome biogenesis, which results in neural crest cell apoptosis, and consequently congenital craniofacial disorders such as Treacher Collins syndrome, and Acrofacial Dysostosis ‐ Cincinnati type. Inhibition of neural crest cell death is capable of ameliorating and in some cases completely preventing craniofacial malformations in mouse and zebrafish models of these syndromes. Through investigating fundamental mechanisms that regulate neural crest cell biology, our work is facilitating the development of therapeutic approaches to prevent the pathogenesis of congenital craniofacial birth defects.

Support or Funding Information

Stowers Institute for Medical Research

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The Value of Anatomy Coursework for Professional School
Authors: Robertson Ellen
Published: June 2021

Some portion of students entering health professional programs each year have had prior coursework in anatomy even if anatomy is not a pre‐requisite course for their given program. Programs training future clinicians in medicine, dentistry, physical and occupational therapy all provide in depth anatomy instruction early in their respective curricula. Who provides this instruction at the professional schools, along with their anatomy teaching background, can vary widely across institutions and professions. In the allied health fields of physical and occupational therapy, the majority of faculty are called out of the clinical ranks to fill teaching vacancies and therefore must pursue terminal degree to satisfy accreditation requirements. Many of these programs call on faculty from outside of the clinical profession, and perhaps even the institution, to teach their courses in anatomy and neuroscience. Graduate programs in anatomy can fill an important gap in the training options for clinicians who are interested in pursuing teaching options within their professional field, or who already have begun.

In many health professional programs gross anatomy is a difficult course, taught early in the curriculum, which can cause students to need remediation and/or face removal from the program. Without knowledge of the students' abilities in the professional program the only source of information about this potential struggle is prior academic coursework and standardized testing usually gathered as part of the admissions application. Throughout the health professions there is research on prior academic coursework and the predictive value towards program outcomes; however, the specific details in regards to anatomy coursework are not as thoroughly researched.

These issues have led to a research study that aims to look at how prior courses in anatomy impact student performance in the health professional gross anatomy courses. The outcomes include both grade performance data and the students' own perceptions of the value of their prior coursework. Even though statistical analyses do not support a grade benefit to the prior anatomy course for medical and dental students, the students perceive it to be tremendously beneficial both at the beginning and end of their professional school gross anatomy coursework. Student perceptions can lead to increased confidence going into a course and also influence the decisions that students make in regards to their study habits.

Future directions for this research include expanding the study to occupational and physical therapy students as well as a comparison across the four disciplines at a major medical center. Outcomes from this project could impact undergraduate pre‐health sciences advising, professional school admissions, and student supports in health professional programs.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The Transition from “Unclaimed Bodies” to Body Donation – an Ongoing Process
Authors: Winkelmann Andreas
Published: June 2021

At a time when dissection as a teaching tool may be replaced by other educational approaches in some programs, and time allocated to it is reduced in others, dissection of a human body is still the cornerstone of anatomical education in most places. Historical developments in this respect are diverse, and anatomists around the world operate within multiple political, legal, cultural, and religious backgrounds to acquire bodies for this purpose. A look at the sources of bodies for anatomy teaching on a global scale reveals that many anatomists still depend on “unclaimed bodies”, while some even have to import bodies from abroad. Today, the ethical gold standard of anatomical dissection is body donation – also officially recommended by the International Federation of Associations of Anatomists (IFAA). While it can be argued that the use of unclaimed bodies can be acceptable for a time of transition in certain circumstances, when without their use anatomical education would be impossible, the aim should nevertheless be the establishment of voluntary body donation programs based on informed consent. The pace of this transition will differ between cultures and countries, but there are encouraging examples, including Taiwan and India, of the recent successful implementation of body donation programs.

Support or Funding Information

no extra funding

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Ethical Questions for Anatomical Body Programs in an Age of Digital Technology
Authors: Cornwall Jon
Published: June 2021

Digital technology is influencing how many teaching institutions use bodies donated to science, with medical imaging procedures, photographs, 3D printing, and genomic information all being increasingly utilized. The increasing use of digitization raises new ethical considerations about how such bodies are used. Elements of information acquisition and communication that were not previously relevant, including ease of data sharing, size and type of data bases, authorization of information transfer, commercialization of information, and incidental findings arising from exome analysis, must now be considered. At present there is a lack of empirical evidence to guide appropriate utilization of this digital information including how acquisition, utilization, distribution, and destruction of such data should take place. The increasing use of digital technology with bodies donated to science raises questions on the nature of informed consent in a digital age, how family involvement in consent processes should be shaped, about anonymity and information sharing, and how potential commercialization of data should be addressed to facilitate the additional benefits such technology may bring to anatomical education.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Reframing Anatomy as a “Safe Space” for Acquiring Professional Competencies: The Role of History and Ethics of Anatomy in Medical Education
Authors: Hildebrandt Sabine
Published: June 2021

In an era of diminishing room for anatomy in medical school curricula, students themselves embrace anatomical dissection not only as a means of learning the structure and function of the human body, but also as an opportunity for the acquisition of professional competencies such as team work, patient–doctor interaction, medical epistemology, and self‐awareness. The anatomical dissection course also presents an opportunity for reflection on medical ethics. One productive approach to the discussion of ethical questions is the study of the history of anatomy, as insights from this history shine a clear light on the present. Ideally, anatomy thus provides not only a new awareness of ethical issues, but also an opportunity for the practice of these new insights in the “safe space” of the labs. Consequently, a new role has developed for anatomists, which includes the interweaving of the scholarly exploration of the history and ethics of anatomy with the practical application of research results into a new concept of ethical anatomical education.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Hippo pathway in nutrient response and cell growth
Authors: Guan Kun‐Liang
Published: June 2021

The Hippo pathway is crucial in organ size control and its dysregulation contributes to tumorigenesis. Core components of the Hippo pathway include the protein kinases of MST1/2, MAP4Ks, and LATS1/2 as well as the transcription co‐activators of YAP/TAZ and their DNA binding partners TEADs. The current paradigm for regulation of this pathway centers on phosphorylation‐dependent nuclear‐cytoplasmic shuttling of YAP/TAZ through a complex network of upstream components that act via the LATS1/2 kinases. We have found that the Hippo pathway is also regulated by cellular metabolism and energy status. There is a functional crosstalk between Hippo and mTOR pathways as YAP/TAZ induces expression of amino acid transporter to promote mTOR activity. YAP/TAZ activity is potently regulated by mechanical signals, such as matrix stiffness. We will discuss new mechanistic insights how the Hippo pathway is regulated by mechano signals.

Support or Funding Information

CA196878GM51586

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Molecular Mechanism of Transcription Transcription‐Coupled Repair
Authors: Wang Dong
Published: June 2021

Progression of RNA polymerase II (Pol II) elongation along the DNA template strand can be blocked by a number of obstructions, including covalent DNA lesions, non‐canonical DNA structures, intrinsic arrest sequences, and small molecules or proteins bound to the DNA. These arrested transcriptional complexes, if not resolved in a timely manner, can be harmful to the cell and increase the risk of genomic instability.

Eukaryotic transcription‐coupled DNA repair is an important sub‐pathway of nucleotide excision repair that preferentially removes DNA lesions from the template strand that block Pol II translocation. This process is initiated by Pol II arrested by DNA lesion and the recruitment of Cockayne Syndrome B protein (CSB) to the lesion‐arrested Pol II. However, the function and molecular mechanism of transcription‐coupled repair initiation have remained elusive.

Here we report our recent structural and functional studies of lesion‐arrested Pol II and Pol II‐CSB complex. These structures provide important structural insights of how DNA lesions are recognized during transcription and the key roles of CSB in both transcription‐coupled repair and transcription elongation. These studies greatly advance our understanding of the molecular mechanism of transcription‐coupled DNA lesion recognition and transcription‐coupled repair initiation.

Support or Funding Information

NIGMS

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Ketones drive mitochondrial uncoupling in adipose tissue
Authors: Walton Chase , Bikman Benjamin T.
Published: June 2021

Objective

The purpose of this study was to determine the effects of the ketone b‐hydroxybutyrate (bHB) on mitochondrial respiration and uncoupling in distinct adipose tissues.

Methods

We used cell, rodent, and human models. 3T3‐L1 adipocytes were treated with bHB; in rodents and humans, following a period of ketosis, fat samples were excised and measured for similar mitochondrial outcomes. In each model, mitochondria respiration was analyzed and, where presently available, UCP1 levels were measured.

Results

In every model, bHB robustly increased mitochondrial respiration. In rodent tissue, UCP1 expression was higher in inguinal fat.

Conclusions

Ketones increase mitochondrial respiration in cells and mammalian adipose tissue, likely via upregulation of UCP1.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Quantitative proteomics for understanding modified proteins and proteomes
Authors: Garcia Benjamin A.
Published: June 2021

Mass spectrometry has become a powerful tool for characterization of thousands of proteins from any cellular source. Here in this presentation, I will highlight advances in mass spectrometry based methodology to detect post‐translational modifications on histone proteins involved in epigenetic regulation of gene expression, dynamics of global protein modifications and to also identify RNA‐protein interaction domains. We will specifically describe high‐throughput comparison of proteins from multiple cellular states (ii) mass spectrometry methods for quantitative tracking of combinatorial modifications (iii) monitoring in vivo post‐translational modification dynamics, and (iv) instrumental methods to improve data acquisition. These studies in combination with biological experiments will help provide a systems biology outlook on gene expression that will lay down the basic scientific foundation to advance several applications, such as stem cell reprogramming and cancer progression.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Seeing the invisible by NMR spectroscopy
Authors: Kay Lewis E.
Published: June 2021

With the ever‐evolving development of new biophysical tools and increasingly powerful techniques for biomolecular structural studies it is reasonable to contemplate the role of solution based NMR spectroscopy in going forward. In this talk I will describe a number of studies on molecular machines from my laboratory, emphasizing the unique role that NMR can play in providing quantitative descriptions of molecular dynamics and how such motion relates to function. The complementarity of NMR to other structural techniques is such that as they continue to advance so to will the utility of NMR. If anything NMR is far more valuable today than it was even a decade ago. This will be emphasized through a number of examples.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Discovery of new roles for zinc in biology from quantitative mapping of zinc in mammalian cells
Authors: Palmer Amy
Published: June 2021

Fluorescent tools have launched biological research into a new realm of understanding of cellular processes and dynamics at the single‐cell level. These tools are enabling characterization of stochasticity and heterogeneity exhibited by biological systems, which could not adequately be probed by techniques that rely on bulk analysis of populations of cells. Fluorescent sensors are increasingly providing insight into the “dark matter” of the cellular milieu: small molecules, secondary metabolites, metals, and ions. One of the great promises of such sensors is the ability to quantify cellular signals in precise locations with high temporal resolution. Yet this is coupled with the challenge of how to ensure that sensors are not perturbing the underlying biology and the need to systematically measure hundreds of individual cells over time. This talk will highlight our efforts to develop genetically encoded FRET‐based sensors for quantitative mapping of zinc ions in cells. I will discuss approaches for defining whether sensors perturb cellular ions, and the specific challenges associated with quantifying ions in cellular organelles. Finally, I will discuss our efforts at systematic quantitative analysis of long‐term imaging of ions during the cell cycle to highlight the need for sophisticated image analysis algorithms. These studies have revealed that zinc is dynamic over the course of the cell cycle and plays an important role in the proliferation‐quiescence cell fate decision.

Support or Funding Information

NIH DP1, NIH GM084027

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Laparoscopic Pancreatoduodenctomy Surgical Training: An Anatomical and Clinical Realistic Simulation Learning Model
Authors: de Moricz André , Thuler Fabio , Barros Mirna Duarte , Mendes Carlos José Lazzarini , Silva Rodrigo Altenfelder , Pacheco Adhemar Monteiro
Published: June 2021

Background

The learning curve in surgical training to perform laparoscopic pancreatoduodenectomy, tends to be long. The surgeon needs to develop advanced laparoscopic skills to accomplish a safe resection and a complex anastomosis like pancreatojejunostomy and hepaticojejunostomy. The low prevalence of pancreatic disease and the risks of leakage and post‐operative pancreatitis during the attempt to perform an adequate anastomosis are some of the major problems related to this surgical learning curve.

Objective

To describe a pancreatoduodenectomy realistic simulation learning model based on anatomical and clinical knowledge of pancreatic and biliary tract morphology, capable to develop and improve surgical skills.

Material and Methods

Using the “EVA Laparoscopica II geração”(Prodelphus Comercio e Industria Importação & Exportação de Simuladores e Equipamentos Médicos Ltda. – www.prodelphus.com.br) (figure 1) as model to simulate an abdominal cavity, we built a resected pancreatic remnant, the liver and choledochal duct, a segment of jejunal loop, located and fixed on the correct abdominal topography similar to the previous recognition of anatomical videolaparoscopy landmarks showed in human anatomy laboratory (figure 2,3). This prosthetic simulator permit to the trainee, the practice of pancreatojejunostomy and hepaticojejunostomy using different technics and surgical material, mimicking the real procedure (figure 4,5,6). This realistic simulation learning model allows the surgeon to improve his surgical skills and permit the instructor to evaluate and teach in real time the position of trocars, tricks of running or separate sutures, knots, drainage and the quality of the anastomosis that are perform using an external catheter infusion system with colored ink In the teaching process, progressive levels of surgical skills can be scored (figure 7,8).

Results

The presented model above had its first test with a group of ten (10) surgeons in a hands‐on laparoscopic pancreatic surgery course last october 2017. The students had different levels of graduation from senior residents with basic laparoscopic training to post graduated and fellows with mild to advanced experience in laparoscopic pancreatic surgery.

Conlusion

This anatomical and clinical realistic simulation learning model permits the development and improvement of surgical skills necessary for surgeons to shorten the laparoscopic pancreatoduodenectomy learning curve.

Support or Funding Information

there is no support or funding

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The return of the Researcher
Authors: Quiroga‐Garza Alejandro , Elizondo‐Omaña Rodrigo Enrique , Guzman‐Lopez Santos
Published: June 2021

A long time (15 yrs) ago, in a medical school far, far away… A few young professors and students set out and started discussing medical articles and research ideas. Soon, an idea was executed and a paper was published. A group began to form, introducing medical students and colleagues into research and publishing, and so, our anatomy research group (GIA) was established. The objective: to be competitive in a constantly changing profession, and against publishing medical schools and hospitals across the world.

Today, GIA receives approximately 25 new students each semester. After a year of introduction course, or 6 months and a research summer, they can apply to interest oriented subgroups (Bone & joints, vascular, central nervous system, peripheral nerves, orbit & eye, head & neck, reproductive, or medical education) as an extra‐curricular activity. Each sub‐group works as a journal club, allowing between 10 – 12 students to work closely with mentors (clinicians and researchers) to develop a morphological based project with clinical relevance, and finish with a publication as first authors. Each student publishes between 1 and 3 papers in indexed journals during the 2 to 4 years they are in the sub‐group. They are constantly exposed to workshops and courses to further their knowledge and experience in their area of interest, as well as research and publishing skills. They are also sent to local and national meetings to present their work as posters or oral presentation. This has attracted more professors and department chiefs from the clinical fields to want to get involved as mentors and publish. It has created new inter‐departmental relationships with stronger and higher impact protocols. Recently graduated clinicians from their specialty, who were involved in the formation of this group and published as students, now return as mentors for new generations, to generate new knowledge, answer questions in their fields, and the motivation to complete a PhD.

This model has shown great advantages for our medical school. It has increased the Anatomy Department's productivity, publishing well over 10 papers yearly during the last 5 years, and the formation of new and better trained researchers in basic and clinical fields. Students who become residents are well prepared and easily perform clinical trials in their fields. It incites more PhDs among professors, it improves the quality and quantity of research, it strengthens the curriculum, and brings stability, uniting MDs with research.

Support or Funding Information

There is no external funding. All funding is provided by our Human Anatomy Department and Medical School.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The Impact of Compulsory Attendance on Anatomy Exam Performance
Authors: Hill Cheryl A. , Greer Sean , Sellers Kaleb , Ward Carol V.
Published: June 2021

Attendance in face‐to‐face anatomy lectures is dwindling since lectures are commonly recorded and viewed outside of the traditional classroom. It is suggested that consistent and engaged lecture attendance generally improves students' performance. Instructors use this information to encourage or require attendance in their face‐to‐face lectures. However, data show an equivocal relationship between compulsory attendance and improved performance. The purpose of this study was to assess the impact of compulsory attendance on exam performance in an undergraduate human anatomy lecture course.

The study sample consisted of two different sections of undergraduate human anatomy lecture with the same instructor (N=821 students). Data were collected for two semesters. Each semester, one section had compulsory lecture attendance, while the other section had optional attendance. Compulsory and optional attendance data were collected by the instructor using an audience response system. The students enrolled in the compulsory attendance section received points for each lecture, while students in the optional attendance section had additional points awarded for the open‐book homework assignments. Three in‐class exams were administered each semester to both sections. Scores for the three exams were compared using one‐way repeated measures ANOVA.

Analyses indicate that compulsory attendance does not result in statistically significant improvements in exam scores for this sample. These results demonstrate that there may be other factors influencing exam performance in anatomical education, including students' engagement, motivation and extracurricular responsibilities.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.