bluuebunny/crossref_metadata_2025_split huggingface dataset:
Teaching Pathophysiology to BSN Nursing Students: Useful Strategies
Authors: Igbo Immaculata , Landson Margie , Straker Kathleen 
Published: June 2021

Pathophysiology is essential for nursing practice and is offered either as a prerequisite or core course for most baccalaureate nursing programs. Learning pathophysiological concepts can be challenging for students, due to variety of factors: family obligations; inadequate study habits; lack of prerequisite knowledge of the biological sciences. However, studies have shown that using a variety of engaging teaching strategies, improve student outcomes (Igbo, Landson, & Straker, 2014; Salamonson, Andrew, & Everett, 2009; and Van Horn, Hyde, Tesh & Kautz, 2014).Consistently, students who were strong in the pathophysiology course were successful on the exit exam used to assess student preparation for the NCLEX. This presentation will discuss active learning strategies: case studies, group presentations, use of immediate response module and online discussions. These strategies increased comprehension and application of the course material as evidenced by improved performance in an exit exam.Igbo, N., Landson, M. and Straker, K. (2014). Nursing Student Retention Strategy: An Integrated Study Skills Elective. Caputi, L. (Ed.). Innovations in Nursing Education: Building the Future of Nursing, Volume 2. Washington, DC: NLN.Salamonson, Y., Andrew, S. and Everett, B. (2009). Academic engagement and disengagement as predictors of performance in pathophysiology among nursing students. Contemporary Nurse: A Journal for the Australian Nursing Profession 32(1‐2): 123‐132.Van Horn, E.R., Hyde, Y.M., Tesh, A.S. and Kautz, D.D. (2014). Teaching pathophysiology: strategies to enliven the traditional lecture. Nurse Educ. 39(1): 34‐7.
Digital microscopy: a new method for histology teaching
Authors: Romana‐Souza Bruna , Porto Luís Cristóvão , Monte‐Alto‐Costa Andréa 
Published: June 2021

The use of digital microscopy combined with Internet facilities has increased in the Histology and Pathology teaching. The aim of this study was evaluated the use of digital microscopy on Histology teaching in the Rio de Janeiro State University. For this, tissue and organ slides were digitalized with Pannoramic Midi (3DHistech, Budapeste). Subsequently, histological structures were identified in the images using Pannoramic viewer (3DHistech). A script was prepared to facilitate the visualization of the image set of each histologic topic by the students. At the end of classes, students answered a questionnaire comparing microscopic based learning lessons to digital microscopy lessons. The digital microscopy was evaluated by 60 dental and 97 medical students from 2013 to 2014. The majority of students (83 percent) found the digital microscopy easy to use, and 89 percent reported that digital microscopy facilitated the identification of the specific structures. A total of 48 percent of students said they learned with digital microscopy more than with microscopic based study. In addition, only 34 percent of students reported that they preferred the microscopic lessons. In conclusion, digital microscopy was found to be evaluated very positively by dental and medical students and may improve learning and productivity in the histology classesFinancial support: Coordination for the Improvement of Higher Education Personnel (CAPES) – Edital Pró‐Ensino em Saúde.
Soft Embalming of Cadaveric Components for Training Purposes
Authors: Sochor Mark , Heltzel Sara , Sikon Dana , Sikon Richard 
Published: June 2021

VA State Anatomical Program (VSAP) has developed soft embalming method (modified Thiel) for research & medical training. VSAP soft embalming technique(VSAP SE) accomplishes realistic tissue feel w/out rapid biological breakdown. Cadavers increasing in expense leading to need for extended retention times. Thus there is increased demand for cadaveric components which fulfill educational needs. Can VSAP soft embalming method be used to embalm cadaveric components (head, arms and legs) from fresh frozen tissue donors. Frozen cadavers sectioned utilizing reciprocating saw which creates clean tissue plane for identifying the blood vessels for injection of VSAP SE fluid. Cadaveric components allowed to thaw over 2 day period to room temperature. Larger arterial vessels identified in each component and smaller collaterals, etc. were clamped off. VSAP SE fluid introduced into the vessels and component was hand massaged for increased fluid penetration. VSAP SE components had excellent results of tissue penetration & soft fixation. Head inspected by ENT surgeons & deemed realistic tissue feel. Arms utilized by orthopedic hand surgeons & legs were utilized for private sports industry anatomical dissection & teaching. Soft embalmed component tissue possible & tissue in this pilot study well received by educators. Multiple educational sessions can be given utilizing same tissue specimen & performance of surgical techniques in step‐wise fashion over several weeks utilizing same component. Research supported by University of VA Center for Applied Biomechanics internal grant & VSAP SE provided by VSAP
Cross‐Course Laboratory Collaboration in Cell Biology and Organic Chemistry II Leads to Increased Knowledge of Science Content and Process
Authors: Carle Sigrid , Miller Justin , Mowery Patricia , MaKinster James 
Published: June 2021

To expose students to interdisciplinary research, provide them with a greater sense of ownership over their work, and model a real research laboratory experience, we linked students in Organic Chemistry II and Cell Biology by focusing on the synthesis and testing of anticancer compounds. To this end Organic Chemistry II students synthesized potential anticancer compounds, known as histone deacetylase inhibitors (HDACi), which were tested for cell cytotoxocity by Cell Biology students.Organic Chemistry II students used standard organic techniques to synthesize novel depsipeptides: peptide bond formation, acyl transfer mechanism, esterification, protecting groups, spectroscopic characterization, and purification techniques. Cell Biology students determined each depsipeptide's IC50 value (or the concentration which kills 50% of the cells) using an MTT assay. Depsipeptides that were cytotoxic were investigated for their ability to induce apoptosis using a CaspACETM Assay.Students in both courses showed statistically significant increases in self‐perceived learning gains in the following subscales: conceptual understanding, integration, and collaborative scientific process understanding. Increases in learning gains were similar between the two courses and were similar for both years of implementation. Organic Chemistry II students also showed gains in individual science process skills while the Cell Biology students did not. Interestingly, there was no significant change in student interest during the semester, in either course, for the first two years of implementation.
Interdisciplinary Learning Communities at Linfield College Increase Interactions Among Students and Participation in Science
Authors: Kruchten Anne 
Published: June 2021

At Linfield College, faculty from multiple disciplines have developed novel STEM programing that includes a week‐long pre‐orientation “boot camp” experience for incoming students, an ongoing learning community program that engages peer mentors in communities working on interdisciplinary problems, and an interdisciplinary seminar series that incorporates both a traditional invited speaker series and preparatory experiences that help undergraduates engage with the advanced material presented by invited speakers.We report here our progress towards our three initial goals. First, we have examined our student population demographics to develop a baseline understanding of the gender, race and ethnicity, first generation status, and transfer status of our students. We use this information to develop programs to retain all students, but especially those who are at risk of leaking from the pipeline. Second, we encourage students and faculty to engage in interdisciplinary research and problem solving in our boot camp, our learning communities, and our seminar series. Third, we have scaled up from ten students per year in a boot camp setting to fifty plus students in learning communities engaging first year students, transfer students, and upper division peer mentors in research projects and discussions. Through pre‐ and post‐ surveys and conversations, we find that students identify more strongly with the experience of “being a scientist” and develop more interdisciplinary connections and communications between first year and upper division students. We believe that the development of a science community through these programs will lead to increased retention of students in our programs.Supported by Linfield College, the Rose E. Tucker Charitable Trust, and the Hearst Foundations Inc.
Checkpoint Regulation of Replication Forks at Sites of DNA Damage
Authors: Iyer Divya , Rhind Nick 
Published: June 2021

Statement of methods:We have used single‐molecule DNA combing to study how the checkpoint regulates individual origins and forks in response to DNA damage.imageSummary of resultsThe S‐phase DNA damage checkpoint slows replication and allows cells to replicate damaged DNA, but how slowing relates to damage tolerance remains unclear. The standard explanation — that checkpoint delays cell‐cycle progression until the damage can be repaired — does not seem to apply in the case of DNA replication. Instead, replication proceeds in the presence of the damage, but at a slower rate. Replication slowing can be achieved by inhibition of origin firing, slowing of fork progression or a combination of both. In bulk assays, 1uM 4NQO and 0.03% MMS slow S phase to a similar extent. However the combing data shows that 4NQO slows replication by reducing origin firing rate, while MMS slows S phase by stalling forks and reducing the fork rate. While reduction in origin firing rate is checkpoint dependent, reduction in fork rate has checkpoint dependent and independent components. We are currently investigating the mechanistic difference in response to different damaging agents and how the checkpoint regulates fork components to achieve replication slowingAnother key question is how forks replicate quickly through damaged DNA in the absence of the checkpoint. The MMS‐induced lesions we use are believed to stop replicative polymerases. Nonetheless, in the absence of the checkpoint, replication forks pass them without any apparent delay. This bypass seems to be mainly dependent on recombination and translesion polymerase based synthesis. We are working on how forks bypass polymerase‐stalling lesions and what effect this bypass has on genomic stability.Funding Source:NIHGMS
CYCLOIDEA Gene Expression across Dipsacales in Relation to Floral Symmetry
Authors: Lim Aedric , Thompson Veronica , Berger Brent , Ricigliano Vincent , Howarth Dianella 
Published: June 2021

The Dipsacales is an order of plants that exhibits a striking shift from radial symmetry in basal lineages like viburnum to strong bilateral symmetry in species like honeysuckle. We are interested in determining how multiple copies of the transcription factor CYCLOIDEA (CYC) may be linked to floral symmetry shifts across Dipsacales. We use quantitative reverse transcriptase PCR (qPCR) to compare relative expression levels of the major copies of CYC (CYC1, CYC2, CYC3) across Dipsacales in seven different species exhibiting radial symmetry, bilateral symmetry, or asymmetry. Our data suggest that radially symmetric species do not exhibit wide variation in expression among petals, whereas bilateral and asymmetric flowers have pronounced differences, especially in CYC2 copiesResearch supported by NSF IOS grant 1121301.
An Ionic Lock Between Intracellular Loop 1 and a C‐terminal Amphipathic Helix Stabilizes the Serotonin Transporter Along its Folding Trajectory
Authors: Sucic Sonja , El‐Kasaby Ali , Koban Florian , Freissmuth Michael 
Published: June 2021

The serotonin transporter (SERT) terminates neurotransmission via rapid reuptake of serotonin from the synaptic cleft. ER export of solute carrier‐6 (SLC6) family members relies on the recruitment of the COPII coat. The COPII component SEC24C binds to an ER export motif located on SERT C‐terminus. We here describe a C‐terminal amphipathic helix that plays a key role in SERT folding. Non‐conservative mutations in the hydrophobic rim of the helix lead to ER retention. Defective ER export of mutant SERTs is not caused by loss of SEC24C binding, revealed by siRNA‐induced SEC24 depletion. ER export of SERT favors inward‐facing transporter conformations. Treatment with the pharmacochaperone noribogaine, which preferentially binds to and stabilizes inward‐facing conformations, recovered the surface expression of C‐terminal helix mutants. Introducing second site suppressor mutations that promote inward‐facing states also repaired their targeting to the membrane. We also probed ionic interactions between the C‐terminus and the first intracellular loop of SERT. Charge‐reversal mutations revealed an ionic lock between E615 in the C‐terminus and R152 in the first intracellular loop. Reversing the charge of each residue alone (R152E or E615K) dramatically reduced SERT surface expression. Conversely, a tandem charge‐reversal mutant (R152E‐E615K) fully restored SERT cell surface expression. We here propose a mechanistic model where the C‐terminal amphipathic helix is stabilized by an intramolecular ionic lock with the first intracellular loop, to support the folding trajectory of SERT and other SLC6 transportersThis work is supported by the Austrian Science Fund Grant P27518‐B27.
Regulatation of hepatic lipid metabolism by glutaredoxin‐1 and protein glutathione‐adducts
Authors: Shao Di , Han Jingyan , Hou Xiuyun , Fry Jessica , Behring Jessica , Yao Chunxiang , Weng Xiang , Pimentel David , Long Michelle , Roy Hemant , Seta Francesca , Cohen Richard , Matsui Reiko , Bachschmid Markus 
Published: June 2021

ObjectiveOxidants can contribute to cellular signaling via glutathione‐(GSH) adducts, which are reversible post‐translational modifications of proteins that alter their function. Glutaredoxin‐1 (Glrx) is an enzyme that specifically removes these GSH‐adducts and modulates enzyme activity. We aimed to study the physiological role of Glrx and protein GSH‐adducts in vivoMethodsWhole body Glrx knockout mice (Glrx‐/‐) were created in a C57BL/6J strain and metabolic alterations were monitored over eight monthsResultsChow fed Glrx‐/‐ mice developed obesity, hepatic steatosis and hyperlipidemia. The key enzyme in hepatic lipid biosynthesis, fatty acid synthase (FASN), was upregulated by 50% in Glrx‐/‐ mice. Liver‐specific adenoviral Glrx reconstitution of Glrx‐/‐ mice down‐regulated hepatic FASN and normalized hepatic and plasma lipid levels. The central metabolic regulator sirtuin‐1 (SirT1), regulates FASN expression. Here, we found that elevated GSH‐adducts on SirT1 in Glrx‐/‐ mice inhibited SirT1 activity leading to increased FASN transcription.ConclusionsOur data suggest that Glrx regulates SirT1 activity in vivo through GSH‐adducts thereby modulating hepatic and plasma lipids.
A lysosomal targeting defect of V0a1 suppresses V‐ATPase activity elevating lysosomal pH in Ppt1‐/‐ mice: amelioration by NtBuHA
Authors: Bagh Maria , Chandra Goutam , Peng Shiyong , Zhang Zhongjian , Mukherjee Anil 
Published: June 2021

Lysosomal pH regulation is impaired in virtually all lysosomal storage disorders (LSDs). However, the mechanism of this defect remains unexplained. The vacuolar H+‐transporting ATPase (v‐ATPase), a multi‐subunit protein‐complex, regulates endosomal/lysosomal pH. The reversible assembly of its membrane‐bound V0 sector and cytosolic V1 sector regulates acidification of the lysosomes. Infantile Neuronal Ceroid Lipofuscinoses (INCL) is a neurodegenerative LSD caused by mutations in the CLN1 gene encoding palmitoyl‐protein thioesterase‐1(PPT1), a depalmitoylating enzyme. Dynamic palmitoylation (palmitoylation‐depalmitoylation) is critical for regulating the functions of many proteins, which requires palmitoyl‐acyltransferases (PATs) for palmitoylation and palmitoyl‐protein thioesterases (PPTs) for depalmitoylation.Using Ppt1‐/‐ mice that mimic INCL, we uncovered that subunit a1 of V0‐ATPase (V0a1) requires palmitoylation on Cys‐25 for localization to endosomal/lysosomal membrane. V0a1 is transported via clathrin/AP2 pathway from plasma membrane to early endosomes where PPT1‐deficiency suppressed depalmitoylation impairing clathrin/AP2/V0a1 dissociation. This defect prevented interaction of V0a1 with AP3, essential for trafficking to lysosomes and clathrin/AP2/V0a1 was recycled back to the plasma membrane. Consequently, disruption of V0/V1 assembly on lysosomal membrane suppressed V‐ATPase activity, essential for pH regulation. Importantly, a PPT1‐mimetic, NtBuHA, ameliorated these defects. Our findings uncover a novel mechanism underlying increased lysosomal pH in INCL and suggest that varying factors impairing V‐ATPase activity may disrupt lysosomal pH regulation in other LSDs.
Development and characterization of synthetic human antibodies for sensing cellular metabolic states
Authors: Tomic Jelena , McLaughlin Megan , Geyer Ron , Sidhu Sachdev , Moffat Jason 
Published: June 2021

Metabolic reprogramming of cancer is reflected in aberrant activity of the hexosamine biosynthetic pathway that produces UDP‐GlcNAc (a donor substrate used to form the O‐GlcNAc modification on proteins). Rather than acting as a switch that turns signaling pathways on or off, O‐GlcNAc should be considered as a “rheostat” that controls the intensity of intracellular signals according to the nutrient and stress conditions. There is evidence that some cell surface proteins contain O‐GlcNAc modification in their extracellular regions. However, there is a lack of understanding for the role of extracellular O‐GlcNAcylation in biological processes.Tuning the level of O‐GlcNAcylation is one way that tumor cells can adapt to varying nutrient and environmental conditions. We hypothesize that cancer cells can “sense” stress through the O‐GlcNAc pathway and, consequently, reprogram the cell surface and adapt to tougher conditions. Neo‐epitopes on the cell surface that emerge from tuning O‐GlcNAc pathway activity may be prime candidates as readouts that reliably report the status of metabolic reprogramming. These nutrient‐dependent cell surface epitopes may have functional roles in defining cancer cell identity.In order to advance understanding of metabolic reprogramming from the perspective of cell surface, we combined genetics and advanced protein engineering using phage‐displayed synthetic human antibody libraries to generate binders that respond to changes in the O‐GlcNAc rheostat. Our method for discovery of surface and nutrient‐associated protein sensors (SNAPS) has allowed us to identify multiple antibodies that can detect different cellular metabolic states.
Assessing Host Immune Response to Dengue Virus Infection at Single‐Cell Resolution
Authors: Sulistijo Endah , Miller‐Jensen Kathryn 
Published: June 2021

Dengue virus (DENV) is a mosquito‐borne pathogen, commonly found in tropical and subtropical climates, that results in a broad range of disease pathologies ranging from asymptomatic to dengue fever (DF) to the more severe dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Despite reports characterizing elevated levels of inflammatory cytokines in serum and correlating the manifestation of the severe disease symptoms to increased immune responses, attempts to delineate the signaling profile have been hindered by the low‐efficiency, dose‐dependent DENV infection of cultured cells. Understanding the signaling profile may reveal the hallmarks of disease progression and dictate the manifested severity of the infection. In this study, we eliminate the complexity of interpreting averaged signaling profile from heterogeneous population by isolating infected cells in a single‐cell barcode chip (SCBC), a device that enable simultaneous detection of multiple secreted cytokines at the single‐cell level. This strategy will allow us to effectively differentiate DENV‐infected from non‐infected cells, profile the types and levels of cytokines and chemokines secreted by these infected cells, and examine how various immune cells response to DENV infection. This single‐cell signaling profile will provide insight into how DENV infection may perturb the host immune system signaling networks and aid in the identification of therapeutic targets that can modulate DENV infection and suppress progression into DHF/DSS.Supported by NIH grant U19‐AI089992
Circadian rhythms orchestrate lymph node homing and egress
Authors: Druzd David , de Juan Alba , Kraus Kerstin , Scheiermann Christoph 
Published: June 2021

Adaptive immunity is dependent on the immunosurveillance of tissues by lymphocytes and their recirculation between blood, lymph nodes and lymph. Thus far, various molecules have been implicated in this migratory process including chemokines and adhesion molecules that play a critical role in the homing and egress events occurring within lymph nodes. However, how this fundamental process of immunity is being regulated at the organismal level at different times is unknown. Here, we present data demonstrating that robust circadian oscillations, exhibiting a period length of ~24h, occur in cellular numbers in murine lymph nodes, showing a ~2‐fold difference with a trough at the onset of the behavioral rest phase (light) and a peak at the onset of the active period (dark). Oscillations were also observed in the capacity of lymphocytes to home to lymph nodes, peaking at the onset of the activity phase. These oscillations corresponded to rhythmic expression of the adhesion molecules ICAM‐1 and VCAM‐1 as well as the chemokine CCL21 within high endothelial cell venules. We detected similar oscillations in leukocyte counts within efferent lymph, exhibiting a ~3‐fold difference between peak and trough values, with egress peaking at the onset of behavioral activity. Egress could be modulated acutely in a rhythmic manner using the functional sphingosine‐1‐phosphate receptor antagonists FTY720 and SEW2871 indicating circadian sensitivity to these drugs. Taken together, our data provide new insights into the temporal control of adaptive immunity by orchestrating the homing of lymphocytes into lymph nodes and their egress from these sites in a rhythmic manner.Funded by the Emmy‐Noether‐Program of the German Research Foundation (DFG)