bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypoxia Upregulates ErbB Family Members in Human Pulmonary Microvascular Endothelial Cells
Authors: Regan Christopher S. , Jin Yi , Pool Caitlyn S. , Liu Yusen S. , Chen Bernadette S. , Nelin Leif D. 
Published: June 2021

Pulmonary hypertension is associated with vascular remodeling that is driven by proliferation of cells in the vascular wall, which involves both endothelial cells and vascular smooth muscle cells. We have previously shown that human pulmonary microvascular endothelial cells (hPMVEC) proliferate in hypoxia, and that hypoxia results in a significant increase in the expression of both epidermal growth factor (EGF) and epidermal growth factor receptor (EGFR/ErbB1). Furthermore, we have shown that hypoxia‐induced proliferation of hPMVEC depends on activation of EGFR/ErbB1. The literature suggests that EGFR/ErbB1 is activated via dimerization, either homodimerization (between the same ErbB family member such as ErbB1:ErbB1), or heterodimerization (between different ErbB family members such as ErbB1:ErbB2). In other cell types, ErbB1, 2, 3 and 4 have been described and the manner by which the ErbB family members dimerize may determine which down‐stream signaling cascades are activated. At present, it is not known in hPMVEC whether all ErbB family members are expressed. As a first step in understanding how ErbB is activated in hPMVEC, we tested the hypothesis that ErbB2, 3, and 4 are expressed in hPMVEC. To begin to address our hypothesis, we incubated hPMVEC in normoxia (21% O2, 5% CO2) at 37° C for 24 hours. Protein was harvested for Western blotting and probed for ErbB1, ErbB2, ErbB3, and ErbB4. We found that hPMVEC express ErbB1, ErbB2, and ErbB4 with only minimal protein expression of ErbB3. To determine the effect of hypoxia on ErbB2 and/or ErbB4 protein expression, hPMVEC were incubated in normoxia or hypoxia (1% O2, 5% CO2) at 37° C for 24 hours. We found that protein levels of both ErbB2 and ErbB4 were greater in hypoxia than in normoxia. In conclusion, our data demonstrate that under the conditions of these experiments, hPMVEC express ErbB1, ErbB2 and ErbB4 protein, with little expression of ErbB3 protein. In addition, hypoxia enhanced ErbB2 and ErbB4 protein expression. These results have important implications for ErbB‐mediated cell signaling in hPMVEC. We speculate that the ErbB members identified in hPMVEC and the mechanism by which ErbB dimerizes represent potential novel therapeutic targets for pulmonary hypertensive disorders associated with hypoxia.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Loss of BMPR2 Confers Proliferative Advantage on Pulmonary Artery Endothelial Cells by Decreasing Dependence on Growth Suppressor Merlin
Authors: Josephs Caleb A. , Ceballos Rhandy , Vasauskas Audrey A. , Morrow Rebekah L. , Morrow Kyle Adam 
Published: June 2021

Pulmonary artery endothelial cells (PAECs) exhibit an abrogated proliferative phenotype when compared to pulmonary microvascular endothelial cells (PMVECs). Pulmonary arterial hypertension (PAH) is a disease characterized by occlusive lesions in the pulmonary vasculature, potentially due to a heightened proliferative capacity of pulmonary endothelial cells. The cytoskeletal linker protein Merlin functions to suppress proliferation in a contact‐dependent manner in a variety of tissues. Loss of Merlin contributes to certain types of lung cancer. Mutations in the bone morphogenic protein receptor 2 (BMPR2) are frequently seen in patients with PAH, and reduced BMPR2 is implicated in a cancer‐like, highly proliferative phenotype of pulmonary microvascular endothelial cells. However, the role of BMPR2 in pulmonary artery endothelial cell proliferation remains unclear. Here, we test the hypothesis that a reduction of BMPR2 confers a growth advantage on PAECs by altering Merlin status. Wild‐type PAECs and PMVECs were grown to sub‐confluence (~80%) or full confluence, cell lysates were harvested, and Merlin levels were assessed. As Merlin functions to suppress growth in a contact‐dependent manner, as expected, PAECs possessed higher levels of Merlin at full confluence than at sub‐confluence. Interestingly, Merlin protein was not detected at sub‐confluence or full confluence in PMVECs. Wild‐type PAECs and PAECs with reduced BMPR2 (BMPR2 knockdown) were assessed for proliferative capacity by traditional and image‐based growth curve analysis. BMPR2 knockdown cells showed increased proliferative capacity when compared with wild‐type PAECs. BMPR2 knockdown and wild‐type PAECs were grown to sub‐confluence and full confluence, cell lysates were harvested, and Merlin levels were assessed. When compared to wild‐type PAECS, BMPR2 knockdown cells appeared to increase Merlin levels to a lesser extent as confluence increased. Thus, we provide evidence of a link between reduced BMPR2 in PAECs contributing to enhanced proliferative capacity, potentially due to a decreased dependence on the growth suppressor Merlin.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effects of Sympathetic Activation on Aortic Stiffness in Young Healthy and Hypertensive Adults
Authors: Lahti Dana S. , Hayward Shayne D. , Wells Calvin R. , McNair Erick D. , Tomczak Corey R. 
Published: June 2021

Aortic stiffness is a major link between hypertension and cardiovascular risk. Anatomic features of the artery including the smooth muscle regulate aortic stiffness, in part. Importantly, vascular smooth muscle is under sympathetic nervous system control, and thus aortic stiffness may be influenced by the sympathetic nervous system. When exposed to physiological stress, older hypertensive adults demonstrate an exaggerated blood pressure response that may correspond with transient arterial stiffness increases, but this response in young hypertensive adults remains unknown.PURPOSEWe tested the hypothesis that sympathetic activation would increase aortic stiffness in young healthy adults (control, CTL), and that aortic stiffness increases during sympathetic activation would be greater in young hypertensive adults (HTN).METHODSSix healthy controls (males=4, females=2; 28.3±5.5 years; BMI: 23.5 ± 3.5 kg/m2) and three young hypertensive participants (males=2, females=1; 28.3±6.0 years; BMI: 30.3±8.2 kg/m2) were studied. Mean arterial pressure (MAP) and carotid‐femoral pulse wave velocity (PWV) were measured at rest and during 5 min of brachial circulatory occlusion (sympathetic activation condition) that followed isometric handgrip exercise.RESULTSResting MAP was higher in HTN (100±6 mmHg) than CTL (90±5 mmHg; P=.029). Occlusion MAP was also higher in HTN (116±6 mmHg) than CTL (102±7 mmHg; P=.016). Resting PWV was similar between CTL (8.6±1.6 m/s) and HTN (8.1±0.1 m/s; P=.47). The increase in PWV from rest to occlusion (1.2±1.4 m/s) in CTL was not significant (P=.09), whereas the increase in PWV from rest to occlusion (2.0±0.4 m/s) in HTN was significant (P=.01).CONCLUSIONSympathetic activation may significantly increase aortic stiffness in young hypertensive adults, but not young healthy adults.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Inhibition of Nitric Oxide Synthase (NOS) by NG‐monomethyl‐L‐arginine (L‐NMMA) Reduces Transient Increase in the Blood‐Brain Barrier Solute Permeability in Rat Brain by Transcranial Direct Current Stimulation
Authors: Fu Bingmei M. , Shin Da Wi , Fan Jie , Khadka Niranjan , Luu Eric , Khalid Wasem , Xia Yifan , Bikson Marom 
Published: June 2021

Transcranial Direct Current Stimulation (tDCS) is a non‐invasive electrical stimulation technique investigated for a broad range of medical and performance indications. Our prior study has shown that tDCS with proper dosage can achieve non‐invasive, selective and temporary increase in the blood‐brain barrier (BBB) permeability (P). To further investigate the cellular and structural mechanisms by which tDCS increases P, prior to 20 min 1 mA tDCS, we pretreated the cerebral microvessels for ~30 min with a NOS inhibitor, L‐NMMA, through the tail vein injection, at an initial blood concentration of ~1 mM. We then used laser scanning multiphoton microscopy with 840 nm excitation wavelength to determine P of the cerebral microvessels in the rat brain tissue 100–200 μm below the pia mater. Sodium fluorescein (MW 376), or FITC‐dextran 70k in 1% BSA mammalian Ringer was injected into the rat (SD, 250–300g) cerebral circulation via the ipsilateral carotid artery by a syringe pump at a constant rate of ~3 ml/min. P were determined from the rate of dye spreading images around individual microvessels in the brain tissue. It was found that L‐NMMA pretreatment significantly reduced the increased P to sodium fluorescein from ~13‐fold to ~4‐fold of its control, and P to Dextran‐70k from ~88‐fold to ~8‐fold of its control at 5 min post tDCS treatment. Treatment by L‐NMMA alone for ~55 min significantly decreased the P to both solutes to ~66% of their controls. The predictions from our previously developed mathematical model for the BBB suggested that increasing the cleft width between adjacent endothelial cells and the width of basement membrane between the endothelium and astrocyte foot processes, due to contracting of endothelial cells, should be responsible for the transient increase in P by tDCS. In contrast, pretreatment of L‐NMMA may strengthen the structural components, most likely the junction strands in the cleft between endothelial cells to prevent the permeability increase by tDCS.Support or Funding InformationNIH RO1 NS101362‐01This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
New Hippocampal Circuit Organization Revealed by Viral‐genetic Tracing and Functional Circuit Mapping
Authors: Xu Xiangmin 
Published: June 2021

The hippocampal formation plays essential roles in learning and memory, and spatial navigation. Although the general anatomy and circuit organization of hippocampal CA1 has been well‐studied, most of our understanding of hippocampal circuits comes from the conventional anatomical tracing studies which lack cell‐type specificity and quantitative measurements of connectional strengths. New advances in virology and molecular genetics complement traditional approaches and are powerful tools for mapping cell‐type‐specific circuit connectivity and function. Using monosynaptic rabies tracing, we recently discovered a non‐canonical but significant set of back‐projections comprised of both excitatory and inhibitory elements from the subiculum to CA1 in the mouse. This discovery suggests previously unconsidered functional roles for direct subicular modulation of hippocampal CA1 circuit activity. In this talk, I will first report our quantitative analysis of canonical‐ and non‐canonical inputs to excitatory neurons in dorsal hippocampal CA1. We find that comparable strength of subiculum complex and entorhinal cortex (EC) inputs to CA1, significant inputs from presubiculum and parasubiculum to CA1, and a threefold stronger input to proximal versus distal CA1 from CA3. Non‐canonical subicular complex inputs exhibit opposing topographic connectivity gradients whereby the subiculum‐CA1 input strength systematically increases but the presubiculum‐CA1 input strength decreases along the proximal‐distal axis. These results reveal a novel anatomical framework by which to determine the circuit bases for CA1 physiological representations. Further, to test the hypothesis that CA1‐projecting subiculum neurons integrate strong CA1 and local subicular inputs to exert direct feedback regulation of CA1 circuit activity, we map and compare global circuit input and output connections of CA1‐projecting and other excitatory subicular neurons using retrograde monosynaptic rabies tracing and anterograde directed herpes simplex virus (H129 strain) in intact brains, respectively. In conjunction with behavior analysis and genetically targeted neuronal activation and inactivation, in vivo GCaMP6‐based calcium imaging of CA1 neurons in freely moving animals is used to resolve how CA1‐projecting subicular neurons modulate CA1 place cell activity and how they contribute to location dependent learning and memory. Together, these studies provide new insights into this subicular‐CA1 pathway, and advance our understanding of how the subiculum interacts with CA1 to regulate hippocampal circuit activity and learning and memory behaviors.Support or Funding InformationThis research is supported by the National Institutes of Health grant (R01NS078434).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Who am I? Investigating the impact of anatomy education on healthcare students' professional identity.
Authors: Lazarus Michelle , Paynter Sophie , Stephens Georgina , Rees Charlotte 
Published: June 2021

Anatomy contact time reductions, in favour of early clinical exposure and professionalism coursework, remain trending in healthcare education. These efforts, have not necessarily improved student classroom to clinic transitions, and may have negative impacts on acquisition of knowledge fit‐for‐practice. In an effort to improve clinical integration and transitions from classroom learning to clinical environments, we evaluated the impact of anatomy education on healthcare students' professional identity and role formation. Using a longitudinal qualitative study approach with Monash University physiotherapy and medicine student participants, we probed students' perceptions regarding the impact of anatomy education on their professional identity development through serial online discussion forums during semester and delved deeper into these discussions by engaging participants in interprofessional focus groups at the end of each semester. Preliminary Framework analysis was undertaken by the research team to identify themes. Preliminary results indicate that there are six themes related to professional identity (PI) and role (PR) implicit in anatomy education: (1) Process, (2) Peer Relationships, (3) Educator Relationships, (4) Ethics, (5) Tolerance of Ambiguity (ToA) and (6) Contexts. Interestingly, some of these themes changed with time and teaching methods (e.g. Ethics), while others appear to be impeded by anatomy education (ToA). Integration of professional development into anatomy education is not only possible, it is an existing (albeit sometimes implicit) component of current teaching practices. Understanding the hidden and informal anatomy curriculum and its impact on PI and PR will not only serve to inform current practices, but it may also help healthcare students improve the ease of transitions (from classroom to clinics to practice). This work will serve as a foundation for builidng a framework which fosters purposeful and explicit integration between anatomy learning and PI/PR development. Together this will foster easier transitions into the clinic by providing students a platform for PI development early in their educational progression.Support or Funding InformationMedical Education Travel Fellowship American Association of Anatomists Travel Fellowship Monash Education Academy Small GrantMonash Facutly of Medicine, Nursing, and Health Sciences Learning and Teaching GrantThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Synergizing Non‐technical Skill Development in Medical Education: From Anatomy Classroom to the In‐Hospital Patient Setting and Back
Authors: Lachman Nirusha , Wittich Christopher 
Published: June 2021

Medical professionalism is a multifaceted concept that includes maintenance of knowledge, interpersonal skills, teamwork, privacy and honesty. While non‐technical skills are often under‐emphasized in the medical student learning environment these skills are directly associated with providing professional medical care. There is an increasing trend however, for basic science courses such as Anatomy to introduce medical students early onto the concept of professionalism and highlight the importance of non‐technical skill development to patient care. To reinforce these competencies as well as develop an authentic curriculum for non‐technical skill development, anatomists and internists at Mayo Clinic, College of Medicine aligned objectives within medical school and residency programs. Strategies were designed to evaluate (1) teamwork, (2) communication and (3) self‐reflection. The aim of this presentation is to demonstrate how each of these core competencies can be promoted in both residency and medical student curricula and how trainee and student progress may be measured by educational approaches within their learning environments. Strategies include the use of a team charter, self‐reflection/reflective diaries and communication exercises that target patients and the multidisciplinary health care team. Through educational design (1) trainee and student's ability to acknowledge self‐limitation and develop critical thinking skills appeared to evolve and (2) trainee and student appreciation of the importance of communication skills when interacting with different groups as well as ability to translate medical/anatomical terminology to lay language were evident. In addition, the use of reflection and team charters promoted understanding team dynamics and facilitation of effective teamwork. The current multi‐disciplinary health care environment places strong emphasis on team‐work, confidentiality of protected health information and the role of communication in preventing medical errors and improving patient outcome. Anatomy courses designed on team‐based approaches with use of body donors provide a useful simulated learning environment. Medical students may be assessed through a variety of activities targeting team‐work, communication skills and clinical reasoning at different levels. Use of reflective exercises assessing team interaction, evolution of critical thinking skills and course challenges have found an important place in the evolving anatomy curriculum. Early exposure to these critical skills helps prepare for clinical rotations where milestones for these skills will need to be reached. This presentation will demonstrate the translational approach in synergizing non‐technical skill development between anatomy and residency curricula.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Identification of Novel Scaffold for PIM1 Kinase Inhibition by Ligand Based Virtual Screening
Authors: Ranganna Kasturi , Mathew Omana P , Milton Shirlette , Thilgavathi Ramasamy , Selvam Chelliah 
Published: June 2021

Prostate cancer afflicts one in six men during their lifetime making this disease the second leading cause of cancer‐related deaths in men in the United States. Given the high prevalence of prostate cancer and the high failure rate of current prostate cancer therapies, development of new therapies for aggressive prostate cancer is a high priority. PIM1 kinase represent as a potential therapeutic target for prostate cancer drug development because they are overexpressed in prostate cancers. There are several PIM kinase inhibitors that have reached to clinical trials and search for the novel PIM1 kinase inhibitor has dramatically accelerated. In silico ligand based virtual high throughput screening is one of the most successful and efficient methods to screen millions of lead like molecules and discover potent lead molecule with novel scaffolds. The present study aim to identify novel scaffolds for selective inhibition of PIM1 kinase by ligand based screening of lead like 4,591,276 compounds from zinc database. A ligand query model with pharmacophore features using vROCS tool was generated by taking a set of well‐known PIM 1 kinase inhibitors. The model was then utilized to screen 4.6 million lead like molecules of ZINC database. The resulted hits were prioritized and purchased 24 compounds from Enamine and Chembridge screening libraries to screen for PIMI kinase inhibitory activity. The PIMI kinase inhibitory activity was performed for all the purchased compounds by using CycLex PIMI kinase assay. The results are displayed in figure 1. The compounds 7, 22, and 23 showed more than 40% inhibition. The best hit molecule identified by ligand based virtual screening is compound 23.Support or Funding InformationThis study was made possible, in part, by Molecular Biology research infrastructure support from grant number 2G12MD007605 from the NIMHD/NIH. We thank the Openeye Inc. for providing the academic license to use the virtual screening tools.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Mass Spectrometry of Bacterial Outer Membrane Enzymes within the Native Lipid Environment
Authors: Esmaili Mansoore , Li Jun , Bishop Russell , Klassen John.S , Overduin Michael 
Published: June 2021

Lipid complexity of bacterial membranes and the dynamic interaction of lipophilic substrates with membrane‐embedded enzymes reflect a demand for a robust detection approach that unravels the local lipids and hydrophobic substrates/products either bound or within the milieu of membrane enzymes. In this study, we used styrene maleic acid lipid particle (SMALP) nanodiscs and electrospray ionization‐ion mobility spectrometry–mass spectrometry (ESI‐IMS) mass spectrometry to address the stability of lipid‐bound states of two bacterial β‐barrel enzymes.We overexpressed and purified different oligomeric states of two model β‐barrel enzymes with their co‐associated lipids (i.e. enzyme substrates/products) from the outer membrane of E.coli using various polymer formulations. We further examined the stability of the intact lipid‐protein nanodiscs in solution as well as in the gas phase. Our results, thus far, has demonstrated the higher efficacy of the native nanodiscs over conventional detergents in isolating lipid populations bound to the enzymes, also an improved thermal stability of the resulting β‐barrel complexes in solution. We have, interestingly, observed that some polymers are more compatible with the required conditions in mass spectrometry hence overcoming limitations (e.g. low pH which is known as destabilizing factor for the original SMALP nanodiscs) in the structural analysis of lipid‐bound states of membrane proteins in the gas phase.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Amyloids and pre‐amyloids from the PDB
Authors: Grolmusz Vince , Takacs Kristof , Varga Balint 
Published: June 2021

Using solely geometric conditions for beta‐sheets, we have prepared and maintain an automatically updated list of amyloid structures from the Protein Data Bank (PDB). Our list contains the insoluble amyloid structures, and, additionally, those globular proteins, which contain amyloid‐like sub‐structures. We assume that these globular proteins are transformed more easily to insoluble amyloid fibrils than other proteins. Several observations from the literature show the validity of this assumption.The list of amyloid‐ and pre‐amyloid structures are publicly available at https://pitgroup.org/amyloid.Support or Funding InformationKristóf Takács was partially supported by the European Union, co‐financed by the European Social Fund (EFOP‐3.6.3‐VEKOP‐16‐2017‐00002).Vince Grolmusz was partially supported by the NKFI‐126472 grant of the National Research, Development and Innovation Office of Hungary.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.