bluuebunny/crossref_metadata_2025_split huggingface dataset:
STAT3 and MEK Mediate IL6‐Induced Increase in Endothelial Permeability
Authors: Alsaffar Hiba , Martino Nina , Adam Alejandro 
Published: November 2023

Interleukin 6 (IL6) has been shown to induce loss of endothelial barrier function both in vivo and in vitro, but the mechanisms involved are not fully understood. Addition of IL6 together with the soluble form of the gp80 receptor (sIL6r) promoted the activation of multiple pathways, including JAK/STAT3, MEK/Erk and PI3K/Akt in HUVEC. IL6 induced an increase in endothelial permeability and loss of junctional VE‐cadherin and ZO‐1, without a reduction of VE‐cadherin or ZO‐1 protein levels. IL6‐induced STAT3 phosphorylation and loss of barrier function was prevented by treatment with the JAK inhibitor ruxolitinib, suggesting that JAK activity is required for these responses. Furthermore, siRNA‐mediated STAT3 knockdown attenuated the loss of IL6‐induced loss of barrier function. Overexpression of a constitutively active STAT3 however, was not sufficient to induce loss of barrier function by itself, suggesting the requirement of other concurrent signaling pathway(s) downstream of IL6. SFK inhibition by pretreatment with PP2 promoted a short delay, but did not prevent the loss of barrier function. Similarly, the PI3K inhibitor LY‐294002 was unable to prevent the increase in permeability by IL6. In contrast, pretreatment with the MEK inhibitor U0126 attenuated the loss of barrier function in response to IL6, suggesting the involvement of MEK activity in IL6‐induced endothelial hyperpermeability. Collectively, our data suggest that the activity of both STAT3 and MEK, but not SFK or PI3K, are required for the loss of endothelial barrier function through a loss of junctional protein localization but not a reduction of protein levels.Support or Funding InformationAHA SDG grant 13SDG17100110
CD99 Regulates Leukocyte Transendothelial Migration Via a Protein Kinase A and Rac1 Dependent Signaling Pathway
Authors: Gonzalez Annette M , Muller William A 
Published: November 2023

CD99, a 32 kD highly O‐glycosylated protein expressed on leukocytes and at the borders of endothelial cells, plays a central role in inflammation through its regulation of transendothelial migration (TEM). Recently, our laboratory reported that CD99 regulates TEM via a process that involves activation of cAMP dependent protein kinase A (PKA) via soluble adenylyl cyclase. Specifically, we showed that activation of PKA is required for the trafficking of the lateral border recycling compartment (LBRC) to the site of transmigration; a step that is required for the passage of leukocytes across the endothelium. The goal of the present study was to identify cellular targets downstream of PKA that are involved in the CD99 signaling pathway for trafficking of the LBRC and TEM. Preliminary data turned our focus to Rac 1. Using a pharmacologic and genetic approach to inhibit Rac1 activity in endothelial cells, we found that leukocyte transendothelial migration was inhibited in endothelial cells that expressed dominant negative Rac1 (N17Rac) but not wild type Rac1. Specifically, the leukocytes interacting with endothelial cells expressing N17Rac were arrested partway through the junction—identical to the phenotype obtained when CD99 is blocked or knocked down—and trafficking of the lateral border recycling compartment was inhibited. We obtained similar results using pharmacologic inhibitors of Rac1 (NSC‐23766 and ET‐1864). Furthermore, an activator of Rac 1 (CNO2) rescued trafficking of the LBRC under conditions where PKA was inhibited and thus restored leukocyte transendothelial migration. In summary, our studies show that CD99 regulates transendothelial migration via a signaling pathway that involves activation of soluble adenylyl cyclase, PKA and Rac1. We hypothesize that CD99 signaling must be spatially and temporally regulated during TEM.Support or Funding InformationThis work was funded by RO1 HL046849 and R37HL064774.
Dynamic modeling shows long‐term gene expression is highly dependent on macromolecular crowding
Authors: Shim Anne Rosati , Almassalha Luay , Matsuda Hiroaki , Nap Rikkert , Szleifer Igal 
Published: November 2023

Chromatin is a polymer of nucleic acids, which contains the cell's hard‐coded genome, as well as additional proteins and complexes which indicate how it should be structured across multiple scales. Although it is highly ordered, chromatin must have the ability to selectively unwind and reposition to allow access to desired genetic information. Although chromatin's dynamic nature is intuitive and increasingly accepted as imperative to nuclear processes, current understanding of the transcription process does not acknowledge the dynamic intracellular environment as a regulator and driver of chromatin structure and transcription kinetics. The intracellular environment of a cell is a system of macromolecular crowding, which creates a dynamic nano‐architecture. This affect both the dynamics and the equilibria of molecular processes and chemical reactions, due in large part to altered diffusion kinetics and binding affinities brought about by depletion interactions between the reacting species and the nano‐architecture. Our previous work demonstrated that transcription is affected non‐monotonically by the steady state volume fraction of crowders in the system. However, dynamic environments are prevalent both in cells at homeostasis, and in many diseased states which experience time‐dependent biomechanical stresses. This property is unexplored, both in theory and in experiment. To study realistic nuclear systems, we have created a temporal model of transcription, which accounts for temporal fluctuations in the nuclear nano‐architecture. This model has shown dynamic forces have a dramatic influence on gene expression, which is highly dependent on both the initial properties of the nucleus and the temporal variations about the initial properties. Though previous models have studied the dependence of gene expression on average nuclear properties, this is the first model to show that temporal variations in the nanoarchitecture alone has the power to alter gene expression, as well as that the frequencies of these variations determine whether gene expression will be upregulated or downregulated.Support or Funding InformationThis research was supported by the Northwestern Physical Sciences‐Oncology Center and the National Institute of Health under award number U01CA202177 in collaboration with Dr. Roger Kamm.
Epistemic Cognition in Medicine: A Review of Literature and Implications for Medical Educators
Authors: Eastwood Jennifer Lynne , Koppelman‐White Elysa , Mi Misa , Wasserman Jason Adam , Krug Ernest F. , Joyce Barbara 
Published: November 2023

ObjectiveAs medical educators increasingly emphasize integration of disciplines, culturally relevant care, and evidence‐based medicine, learners must draw upon diverse ways of knowing and learning. Because learners' theories of knowledge and knowing influence how they reason and make meaning, it is important to consider how these theories, described as epistemic cognition, relate to medical education and practice. The purpose of this presentation is to present a review of the research literature on epistemic cognition in medicine and discuss implications for health science and medical educators.MethodsFollowing recommendations for systematic review described by Cook and West (2012), we conducted database searches using keywords related to epistemic cognition and medical education. Requirements for selection included empirical studies with a central focus on epistemic cognition and participant samples including medical students or physicians. Independent thematic analysis and consensus procedures were used to identify major findings about epistemic cognition in medicine and implications for research and medical education. Ongoing updates to the literature within our search parameters will be incorporated in the presentation.ResultsThemes from the findings of selected studies included relatively simple epistemological positions of medical learners, increasing epistemological sophistication with clinical experience, and relationships between epistemic cognition and the context of medical education and practice. Other common themes included patterns in epistemic orientations to clinical practice and learners' and physicians' reactions to ambiguity and uncertainty. Many studies identified the need for new instruments and methodologies to study epistemic cognition in medicine and its relationship to clinical outcomes. Also, relationships between epistemological positions and humanistic patient care, as well as influences of medical education practices were identified as important areas for future study.ConclusionsThe concept of epistemic cognition is presented and applied in different ways in the medical research literature. Advancing theoretical frameworks and developing new methodological approaches to examine epistemic cognition are important next steps. Additionally, future research should examine the relationship between the contexts of medical learning and practice and epistemic cognition. For example, do teaching and assessment in medical education promote conceptions of certainty and concreteness of medical knowledge? If so, how can medical educators from various disciplines promote more beneficial epistemic positions? Finally, we will discuss implications of epistemic cognition for development of humanistic orientations to medical care.Support or Funding InformationArnold P. Gold Foundation
Clinical Research 101: a Way to Showcase Healthcare Professions in High‐School students using PhUn week
Authors: Gurovich Alvaro N , Morales Francisco , Terry Kim 
Published: November 2023

According to the Area Health Education Center (AHEC), there is a shortage of health care professionals in the country, especially in rural areas. In addition, and according to the NSF, there is a shortage of students choosing STEM careers. To tackle these problems, the American Physiological Society (APS) and AHEC have created programs to increase the likelihood of high school students to choose science and health care professions paths, respectively. Physiology Understanding (PhUn) week is an APS outreach program looking to motivate K‐12 students to choose science programs as their higher education path. On the other hand, AHEC has several grant mechanisms to fund K‐12 and undergraduate activities looking to engage students toward health care professions. Here, we combined PhUn week, health education, and high technology to introduce high school students to clinical research. A one‐full day session was designed for upper science class (juniors and seniors) that had 3 phases: 1) discussion about a health problem that could be targeted for clinical research and the study design, 2) data collection, and 3) data analysis and conclusions. Fifteen undergraduate students were involved designing the different hands‐on activities to perform during the full day session. Forty high school students attended the session and actively discussed the needs of clinical research in cardiovascular (CV) disease. During phase 1, the students were able to identify several CV risk factors such as stress, obesity, and fitness levels. In phase 2, students were divided in 4 groups for data collection in 4 different stations. Station one collected stress levels (using a standardized survey) and blood pressure; station 2 collected height, weight, and %fat mass (using a Tanita scale); station 3 collected heart rate recovery after 2 minutes of moderate intensity exercise (using Biopac MP40 system); and station 4 collected autonomic nervous system activity via changes in heart rate (using Biopac MP40 system). In phase 3, students were asked to enter their data in an Excel spreadsheet for data analysis. Once all data from all 40 students was combined, life data analysis was performed with feedback from the audience about what associations to look for. Finally, all collected data was left with the science teacher for any further analysis the students wanted to perform. Motivating students from rural areas to choose STEM or health care professions path is not an easy task. Based on the level of engagement of all students, we strongly suggest using applied high tech activities, such as this PhUn week activity.Support or Funding InformationSupported by IU AHEC 16/17 #PIU535 and APS PhUn week program
Course‐embedded Undergraduate Research in an Animal Physiology Laboratory Course
Authors: Liu Sumei 
Published: November 2023

It is widely accepted that undergraduate research experience enhances scientific education. A well‐established approach to provide undergraduate research opportunities is to have students work in a faculty's laboratory. The large number of Biology Majors at most comprehensive universities makes this approach highly challenging. Course‐embedded undergraduate research experience (CURE) has been proven to be as beneficial to students as the traditional faculty‐mentored research. Different types of research projects have been used in CURE. This course differed in that students worked as co‐investigators with the faculty on a small subtask of a large research project. The overall aim of this particular large research project is to investigate the role of gut microbiota on gut motor functions in irritable bowel syndrome. One approach to study the impact of gut microbiota on health and diseases is to deplete the gut microbiota by using a broad‐spectrum antibiotic cocktail. The antibiotics may influence gut motility directly by activating receptors on the smooth muscle cells or indirectly via depletion of gut microbiota. The student experiment was designed to test the direct effects of the antibiotics on gut smooth muscles. During the first twelve weeks, students performed six pre‐designed experiments, among which one lab was to study gut smooth muscle motility. The last three weeks were reserved for independent research. Students were responsible for searching relevant primary literature, designing the experiments, determining the materials and equipment needed, performing the experiments, and analyzing the data. Students reported their findings in the format of an original research journal article. Pre‐ and post‐tests were administered to assess student learning gain of physiological concepts and research skills. A post‐course survey was conducted to assess student attitudes toward scientific research. The results suggested that although this CURE approach didn't significantly enhance student learning gain in physiological concepts, it helped to build student research skills. The post‐course survey results suggested that performing independent research increased students' understanding of research, increased their confidence in doing research, and made them proud of their contribution to faculty research. This co‐investigator approach could be easily adapted to a CURE in other biology courses.Support or Funding InformationThis work was supported by a grant from Center for Advanced Teaching and Learning, University of Wisconsin‐La Cross.
A Model for Enhancing Student Gains During Experiential Learning Opportunities
Authors: Halpin Patricia A. , Donahue Ann E. , Johnson Kathryn M.S. 
Published: November 2023

Experiential learning (EL) is the core component of a required undergraduate capstone course at a small public academic institution in the Northeast. During their senior year, students fulfill their EL requirement beyond the classroom by performing research, an independent study, or an internship. After completion of, or concurrent with their EL experience, students are enrolled in the Senior Seminar course. This course emphasizes written and oral communication skills as well as career preparation. At the conclusion of the Senior Seminar course, students are assigned a reflective paper assignment prompting them to discuss the value derived from their EL experience and connecting their experience to their future professional goals. In previous semesters these reflective papers often demonstrated limited depth and failed to connect the students' current and future work. In order to create opportunities for students to strengthen reflective writing skills, the Senior Seminar course was redesigned to include weekly interventions that included intentional reflective exercises. Using the course management system to facilitate the process, students completed the reflective exercises and the professor committed to providing timely feedback each week.Support or Funding InformationNational Science Foundation UNH Advance Visiting Women Scholar Grant
Aligning Introductory Biology to Vision and Change Recommendations
Authors: Wilkinson Katherine A. , Lambrecht Susan , Anand Sulekha 
Published: November 2023

The SJSU Biological Sciences Department is in the process of redesigning the core introductory biology sequence to align with the best practices in biology pedagogy as described in the Vision and Change in Undergraduate Biology Education report. Introductory Biology is a two semester series with a high failure rate (20–30%). Our goal is to improve student performance in the course and student preparation for success in the major. We have reorganized the lecture topics to focus on the core competencies and concepts identified in Vision & Change and are making an effort to emphasize depth and not breadth of information. We have adopted a low‐cost digital textbook, Integrating Concepts in Biology by Campbell, Heyer, & Paradise, which emphasizes experimental data and the core concepts. We are also developing active learning activities for the lecture, including reading pre‐quizzes, in‐class clicker questions, and SJSU faculty research highlights. We are also incorporating more inquiry based laboratory activities. Finally, we are taking advantage of university resources to offer peer mentor facilitated homework sessions. To assess the success of our redesign and aid in our understanding of the student population that takes these courses, we are administering two validated concept inventories, the Biology Concept Inventory (BCI) and the Test of Scientific Literacy Skills (TOSLS), and a demographic survey at the beginning of the first course and the end of the second course. Pre‐test scores from the previous version of the courses (BIOL 1A and 1B) indicate that first generation college students (1st Gen) had lower scores on average than students who are not 1st Gen on the TOSLS, but not BCI. Under‐represented minority students (URM), which comprise African American, Alaskan or American Indian, and Hispanic/Latino students, had similar scores as non‐URM students on both the TOSLS and BCI. This suggests that 1st Gen students, but not URM students, are entering Introductory Biology with poorer preparation. Overall pass rate in BIOL 1A was 80%, however, both 1st Gen and URM students were less likely to pass BIOL 1A (1st Gen = 71%, URM = 69%, 1st Gen & URM = 64%). We will be assessing the effect of our redesign on overall student performance in the Introductory Biology sequence as well as its effect on the achievement gap.Support or Funding InformationThis work was supported by a California State University Program in Education and Research in Biotechnology (CSUPERB) Curriculum Grant.
Lessons from Fundulus melanophores: integrative approach in biology education
Authors: Hong Seung Mook 
Published: November 2023

A three‐credit investigative physiology lab (Experimental Physiology, BISC316) is offered to biology upper classmen once they have completed the prerequisite lecture course, General Physiology (BISC306). This is a short‐term research course, and the main research theme revolves around physiological color change in animals with an emphasis on the role of dermal melanophores in killifish (Fundulus heteroclitus). After spending a half the semester on honing basic experimental skills, 3–4 students in groups address in a series of experiments their own research question on animal color changes based on experimental data in the literature. One purpose of this course is to provide a wet‐science research experience to a broader population in biology majors, which additionally satisfies a university requirement for “Discovery Learning Experience”. The dermal melanophores in Fundulus heteroclitus have been a useful model system for classroom research due to its fast time course for highly visual physiological responses along with a wealth of information in the literature. In addition, this physiological process can be tested at multiple levels from organism to tissue to cell, readily crossing over between disciplines in biology. Various hurdles in creating this inquiry‐based learning environment for class have been identified in the previous study, which in turn provided opportunities to collaborate with experts in English and Cell Biology as well as some untapped biology undergraduates. In the current study, a new teaching module was explored to extend a research experience to freshman students enrolled in the first‐semester sequence of Introductory Biology (BISC207), which is part of 8‐credit integrated biology‐chemistry course. A series of research‐related activities concluded with an oral presentation by groups at the end of the semester, in hopes to encourage students to reflect and integrate biological functions with chemical structures presented in the primary literature.Support or Funding InformationSupported by HHMI
Inspection of Medical Students' Quality of Life in An Unstable Nation, Yemen: Is WHOQOL‐BREF Still Valid and Reliable?
Authors: Ba Abbad Abdulrahman Ali , Alaidroos Hussien Abdullah , Bawazir Ahmed , Al‐Gunaid Mohammed Abdulrahman , Al‐Ghurabi Mohammed Omar , Abdulwali Fareeha Kaiser , Obad Adam Subait , Shareef Mohammad Abrar 
Published: November 2023

IntroductionThe World Health Organization Quality Of Life‐BREF (WHOQOL‐BREF) questionnaire has been widely used and extensively validated in different languages. While it has been shown to be a valid and reliable gauge among medical students in many stable countries, its validity and reliability among medical students in an unstable country was not yet assessed. Hence, the aim of this study was to validate the questionnaire among Yemeni medical students and assess their quality of life.MethodsAn anonymous, self‐administered and previously validated Arabic version of the WHOQOL‐BREF questionnaire was distributed among medical students of Hadramount medical college, Yemen. Confirmatory factor analysis and Cronbach's alpha were used to assess the validity and reliability of the questionnaire, respectively. Quality of life scores were calculated and reported following the WHO manual of the questionnaire.ResultsA total of 416 responses were retrieved and subjected to analysis. After excluding questions 3, 4, and 21 the questionnaire showed good validity with the least loading factor value of 0.37 when four‐factor priori model is adopted. Additionally, the instrument has demonstrated an excellent internal consistency (Cronbach's α 0.891). Mean scores in physical, psychological, social and environmental domains were 13.51, 14.29, 14.65, and 12.23, respectively.ConclusionThe Arabic version of the questionnaire was valid and reliable to assess the quality of life among medical students in Hadramout medical college. The instrument has detected low overall score and low scores in physical, psychological, social, and environmental aspects of life in comparison to previous studies in stable countries. Therefore, necessary support is required to enhance their quality of life and additional studies are required to postulate and implement solutions.Support or Funding InformationWe would like to thank Hadramout University, faculty and students for their support and help in completing this study. Special thanks to our 4th year colleagues in Hadramout University, College of Medicine : 1) Muhammad Salah Al‐Qu'aiti, 2) Abdullah Salem Bahadi, 3) Ashraf Fahed Basalelah.