bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome‐wide discovery of gene isoforms expressed in primary smooth muscle cells
Authors: Ro Seungil , Park Chanjae , Park Paul J , Berent Robyn , Collins Nicholas , Syn Hannah , Chin Albert , Sanders Kenton M
Published: June 2021

Smooth muscle cells (SMC) display remarkable plasticity leading to development of several medical conditions that impair the normal functions of SMC. Given the importance of their pathophysiological roles, SMC have been studied extensively for several decades, which has led to the identification of many SMC‐specific genes. However, a comprehensive expression profile and genetic information of SMC, which is necessary for understanding all functional roles of these cells, remains elusive. In order to achieve this goal, we isolated primary SMC from small intestine and colon of smMHCCre‐eGFP/+ mice, which labeled all differentiated SMC. By using deep DNA sequencing technology, we obtained the transcriptome of SMC. The transcriptome revealed thousands of new isoforms that were uniquely expressed in SMC. The SMC‐specific isoforms consisted of hundreds of contractile genes, ion channels, and receptors, which implicated their functional roles in contractility. We built a SMC genome browser using the UCSC genome custom track. The genome browser provides a valuable reference for future functional studies of SMC. The database also serves as a reference for conditions in which differentiated SMC are phenotypically changed in pathological processes. This genome‐wide transcriptome analysis brings new insight into the genetic structure, expression profile, and isoforms of each individual gene expressed in SMC.
Gene expression profile underlying accentuated skeletal muscle wasting in chronic alcohol‐fed simian immunodeficiency virusinfected macaques
Authors: Dodd Tracy y , LeCapitaine Nicole J. , Zabaleta Jovanny , Voloshenyuk Tetyana , Dufour Jason P , Bagby Gregory J. , Nelson Steve , Molina Patricia E.
Published: June 2021

Chronic binge alcohol (CBA) accentuates skeletal muscle (SKM) wasting at terminal stage of simian immunodeficiency virus (SIV) infection. The purpose of this study was to identify differentially regulated genes that may contribute to SKM in CBA SIV‐infected macaques (CBA/SIV) vs. sucrose‐fed SIV‐infected macaques (SUC/SIV). Transcriptome of SKM samples obtained at necropsy (~10 mo post‐SIV) from CBA and sucrose‐SIV‐infected macaques were compared using Illumina Custom algorithm to compare the level of gene expression (p‐value filter of ≤ 0.05, either ≥ 3‐fold change or ≤ 0.35‐fold change). A total of 836 genes were shown to be differentially regulated between the SUC/SIV and CBA/SIV animals. Further filtering of the gene pool revealed 21 significantly upregulated and 26 significantly downregulated genes that were examined through literature searches based on their functional consequences as they relate to muscle wasting. Five of the 21 upregulated genes (HP, CCL‐2, SELE, TIMP‐1, and PAPPA) and six of the 26 downregulated genes (ATP2B2, PP1R3C, TAOK1, PVALB, APLN, ESR1) were selected for further analysis based their relevance to mechanisms underlying muscle wasting. Verification of the selected genes through quantitative real‐time PCR and Western blot analysis followed by in vitro functional assays will confirm their contribution to the mechanisms underlying accentuated skeletal muscle wasting in CBA SIV‐infected macaques. Supported by: AA‐07577, AA‐09803, AA‐11290.
A novel PGC‐1á isoform induced by resistance training regulates skeletal muscle hypertrophy
Authors: White James , Ruas Jorge , Rao Rajesh , Kleiner Sandra , Wu Jun , Spiegelman Bruce
Published: June 2021

PGC‐1α is a transcriptional coactivator induced by exercise that gives muscle many of the best known adaptations to endurancetype exercise, but has no effects on muscle strength or hypertrophy. We have identified a novel form of PGC‐1α (PGC‐1α4) that results from alternative promoter usage and splicing of the primary transcript. PGC‐1α4 is highly expressed in exercised muscle but does not regulate most known PGC‐1α targets such as the mitochondrial OXPHOS genes. Rather, it specifically induces IGF1 and represses myostatin, and expression of PGC‐1α4 in vitro and in vivo induces robust skeletal muscle hypertrophy. Importantly, mice with skeletal muscle‐specific transgenic expression of PGC‐1α4 show increased muscle mass and strength, and dramatic resistance to the muscle wasting of cancer cachexia. Expression of PGC‐1α4 is preferentially induced in mouse and human muscle during resistance exercise. These studies identify a novel PGC‐1α protein that regulates and coordinates factors involved in skeletal muscle hypertrophy.
Enalapril attenuates the exaggerated sympathetic response to physical stress in prenatally programmed hypertensive rats
Authors: Mizuno Masaki , Lozano German , Siddique Khurrum , Baum Michel , Smith Scott A.
Published: June 2021

Prenatal programming induced by maternal dietary protein deprivation (6% vs 20% protein diet) results in hypertension in adult rat offspring. We have shown that the hypertension with prenatal programming (PPH) is due to increased sympathetic nerve activity. The purpose of this study was to examine if angiotensin‐converting enzyme (ACE) inhibition would attenuate the enhanced sympathetic response to acute physical stress in PPH. To test this postulate, changes in renal sympathetic nerve activity (RSNA) to stimulation of the skeletal muscle exercise pressor reflex (EPR) were assessed in controls and PPH rats chronically treated (from age 4 wks) with either vehicle or enalapril (an ACE inhibitor) in their drinking water. Adult male offspring (age 16–20 wks) were studied. Resting systolic blood pressure (SBP) was greater in PPH than control in vehicle treated groups and the blood pressure was normalized by enalapril in the PPH group. The RSNA response to EPR stimulation was significantly higher in PPH than control in vehicle treated groups. Enalapril treatment significantly attenuated the RSNA response to EPR activation in PPH but had no effect in control rats. These results suggest that angiotensin II contributes to the generation of stress‐induced sympathetic overactivity in PPH. Further, this enhanced sympathetic responsiveness can be reduced by ACE inhibition. Supported by NIH HL‐088422, DK41612 and DK078596
Effect of aging on the hemodynamic and sympathetic response at the onset of isometric handgrip exercise
Authors: Lalande Sophie , Sawicki Carolyn P , Baker Jacquie R , Shoemaker J Kevin
Published: June 2021

This study determined whether sympathetic inhibition occurs at the onset of isometric handgrip exercise (HG). We also determined whether age affects the hemodynamic and sympathetic responses to HG. Twelve young and 16 older individuals (age: 24 ± 3 vs.60 ± 9 years) performed four 20‐second HG at 30, 40 and 50% of maximum voluntary contraction (MVC). Beat‐by‐beat heart rate (HR), mean arterial pressure (MAP), cardiac output (Q) and total peripheral resistance (TPR) were assessed by Modelflow, and burst frequency and burst incidence of muscle sympathetic nerve activity (MSNA) were obtained by microneurography. Baseline MSNA burst frequency and incidence were higher in older vs. young individuals (24±9 vs. 12±5 bursts/min, 41±14 vs. 18±8 bursts/100 heartbeat, p<0.001). At 30% MVC, there was no HG effect on HR, MAP, Q, TPR, bursts frequency and incidence in comparison to baseline. At 40% MVC, HG increased HR alone (main effect, p=0.01). At 50% MVC, HG increased HR and burst frequency (main effect, p<0.01). An age effect was observed at 50% MVC, where HG increased HR to a greater extent in young vs. older individuals (15±10 vs. 8±5 bpm, p=0.02). There was no evidence of sympathetic inhibition at the onset of HG in either young or older individuals. Age reduced the HR response but had no impact on the sympathetic response at the onset of HG. This study was funded by CIHR.
The effects of increased plasma volume on autonomic control of the circulation after a bout of intense‐intermittent exercise in men
Authors: Okazaki Kazunobu , Takeda Ryosuke , Suzuki Akina , Naghavi Nooshin , Imai Daiki , Miyagawa Toshiaki
Published: June 2021

Plasma volume (PV) after a bout of intense‐intermittent exercise is reported to be increased by protein and carbohydrate (CHO) intake just after exercise. The possible effects of the increased PV on autonomic control of the circulation after exercise remain unknown.

METHODS

Seven healthy men (≈23 yrs) underwent two trials those of which differ in the timing of intake (just after exercise, 0H; and 2 hours later, 2H) of protein and CHO (3.2 kcal and 0.18 g protein/kg). After baseline (BL) in a seated position, subjects performed a 72‐min intense‐intermittent exercise (8 sets of 4 min at 80% VO2max + 5 min at 20% VO2max), then they kept seated rest during 0–5th and 22–23rd hour of recovery. Percent change in PV from BL (Δ%PV) was determined and beat‐to‐beat blood pressure, R‐R interval, heart rate, and stroke volume (SV) were measured during 5‐min spontaneous and fixed rate (0.2 Hz) respiration at BL and every hour during recovery. Dynamic arterial‐cardiac baroreflex sensitivity (BRS) was calculated by sequence analysis.

RESULTS

Δ%PV in 0H was higher than 2H at 5th and 23rd hour of recovery. There was no difference in BRS between trials while SV and effective arterial‐cardiac baroreflex gain estimated as BRS ~SV were higher in 0H than 2H at 5th and 23rd hour of recovery.

CONCLUSION

Increased PV enhances the effectiveness of autonomic circulatory control with increased SV after an intense‐intermittent exercise.
Intestinal barrier components are similarly altered in restraint and social defeat stress
Authors: Onyango Edward M , Habiyambere Bupe M
Published: June 2021

The protective intestinal mucosal barrier consists partly of mucin proteins produced by mucosal epithelial cells. This study compared the effects of 2 different types of stress (restraint stress, RS; and social defeat stress, SDS) on components of the intestinal mucosal barrier particularly the mucin‐producing cells. The overall study involved 4 mice groups of 8 mice each. Effect of RS was tested using 2 groups: a test group exposed to RS for 21 days and a control group that was not exposed to the stress. The remaining 2 groups were used to test the effect of SDS: a test group that was exposed to SDS and a control group that was not exposed to the stress. Mice were euthanized at the end of the test period and intestinal portions were removed and fixed in methacarn, embedded in paraffin, sectioned and stained using Alcian Blue‐Periodic acid Schiff to visualize the mucin‐producing goblet cells and measure villi lengths. Histology showed a decrease in the number of goblet cells in stressed mice compared to control mice regardless of the type of stress (P<0.05). Similarly villi length was lower in stressed mice compared to control mice for both stress types (P<0.05). The findings suggest that stress of either type seems, in a similar manner, to affect the dynamics of mucin production and the overall absorptive and protective surface of the mouse intestine.

Research was supported by East Tennessee State University.
Ovariectomy reduces Visceral Hypersensitivity in Female Serotonin Transporter (SERT) Knockout (KO) Rats
Authors: Fried David E. , Galligan James J
Published: June 2021

Visceral hypersensitivity (VH) is a symptom in irritable bowel syndrome (IBS), particularly in women and symptom severity varies over the menstrual cycle. Disrupted serotonin signaling, including reduced SERT expression, occurs in some IBS patients. We studied VH in male and female SERT KO and wild type (WT) rats to determine if SERT deficiency and the estrous cycle were associated with VH.

Methods

VH was measured using the abdominal electromyographic visceromotor response (VMR) to colorectal balloon distention (CRD). We also assessed somatic hypersensitivity using the hot plate test. Ovariectomized (OVX) SERT KO and WT rats were used to investigate the effects of gonadal hormones on VH.

Results

The VMR to CRD was increased in female but not male SERT KO rats (P<0.05); the maximum response occurred during proestrus. The VMR was greater in female SERT KO vs. female WT rats. OVX reduced VH in female SERT KO rats (P<0.05). There were no differences in somatic thermal sensitivity between female WT and SERT KO rats.

Conclusions

There is an interaction between increased serotonin availability (as occurs in SERT KO rats) and female gonadal hormones that results in VH. This mimics symptoms occurring in female IBS patients. The SERT KO rat may be a useful model for mechanistic studies of interactions between sex, serotonin and visceral sensation.
Resistance to hypoxia‐induced programmed necrosis is conferred by glycolytic pyruvate scavenging of mitochondrial superoxide in colorectal cancer cells
Authors: Huang Ching‐Ying , Kuo Wei‐Ting , Huang Yi‐Cheng , Lee Tsung‐Chun , Yu Linda Chia‐Hui
Published: June 2021

Increased glucose transporters (GLUTs) and anaerorobic glycolysis, implicated as adaptive responses to hypoxic stress, were found in peri‐necrotic regions in human colorectal carcinoma. Receptor‐interacting protein (RIP) signaling and mitochondrial reactive oxygen species (ROS) are involved in necrotic pathways. Our aim was to explore the underlying mechanism of glucose‐conferred resistance to hypoxia‐induced cell necrosis. Caco‐2 cells hypoxia exposed in glucose‐free media displayed LDH leakage and RIP‐1/3 complex formation, which may be inhibited by necrostatin‐1 and gene silencing of RIP1. Normoxic counterparts showed no sign of necrosis. Inhibition of mitochondrial superoxide production by antioxidants also decreased LDH leakage. Addition of glucose and pyruvate derivative, but not non‐metabolizable analogs, diminished RIP‐dependent LDH leakage. Hypoxic cells with glucose showed HIF1α activation and hypoxia‐targeted gene (GLUT‐1 and ‐4) expression. Glucose increases ATP and pyruvate levels, whereas pyruvate derivative did not change the ATP level in hypoxic conditions. Pyruvate decreased hypoxia‐induced mitochondrial superoxide levels and was involved in anti‐necrotic mechanisms. In conclusion, glycolytic pyruvate confers resistance to RIP‐dependent necrosis in hypoxic cancer cells through mitochondrial ROS suppression. Funding support by National Science Council and NTU.
Amino acid absorption by lobster (Homarus americanus) intestine using dual‐label radioisotopic tracer techniques
Authors: Rasidovic Mihra , Ahearn Gregory A
Published: June 2021

Amino acids are transported from the lumen of an intestine to the blood across epithelial mucosal and serosal membranes by specific amino acid carrier proteins found within the membrane as well as a transport process involving bis complex formation between the amino acids and metal ions resulting in a dipeptide‐like substrate. In this study the absorption of 3H‐L‐leucine and 35S‐L‐methionine across lobster intestine were simultaneously followed in the presence and absence of Zn metal ions using dual‐label radioisotopic tracer techniques allowing the analysis of independent amino acid fluxes in single experiments. The radiolabelled amino acids were perfused through in vitro lobster intestines and rates of isotope appearance were periodically monitored to estimate trans‐intestinal fluxes of each amino acid. In the presence of luminal Zn, both 3H‐L‐leucine and 35S‐L‐methionine fluxes across the tissue were significantly stimulated. There was no significant evidence that the amino acids competed with each other for carrier transport in the absence of Zn, suggesting separate amino acid transport systems for these substrates. On‐going experiments will determine if bis‐complexes of these amino acids, involving Zn, enhance amino acid flux rates to the serosa, and if there are competitive interactions between the complexes. Agriculture and Food Research Initiative Competitive USDA Grant no. 2010–65206‐20617.
The Dual Roles of Aromatic Residue Y67 in Claudin‐2 Pore Cation Selectivity
Authors: Li Jiahua , Zhuo Min , Pei Lei , Yu Alan S.L.
Published: June 2021

In tight junctions, claudin‐2 forms a paracellular cation selective pore by interaction of the first extracellular loop (ECL 1). When all negatively charged residues in the claudin‐2 ECL 1 were mutated to neutral amino acids, the pore became less cation selective but remained four times more selective to Na+ than to Cl‐, suggesting other non‐charged amino acids may also contribute to cation selectivity. We hypothesized that Y67, a conserved aromatic residue near the pore selective filter, contributed to cation selectivity by cation‐pi interaction with the permeating cation. We generated stably transfected claudin‐2 Y67 mutants in MDCK I Tet‐off cells. Y67L partially lost cation selectivity due to decreased Na+ permeability without affecting Cl‐ permeability. Y67A enlarged the pore size and further decreased cation selectivity due to an increase in Cl‐ permeability. The Y67C accessibility assay suggested Y67's side chain pointing to the lumen of the pore. In conclusion, we demonstrate that the conserved aromatic residue at site 67 contributes to cation selectivity by a dual role of a cation‐pi interaction and a steric effect. Supported by NIH grants R01DK062283, R01DK062283–07S1 and U01GM094627.
Simulated microgravity increases susceptibility of intestinal epithelial cells to acetaldehyde‐induced barrier dysfunction
Authors: Stork Cheryl A , Marchelletta Ronald R. , Prisk G. Kim , McCole Declan F.
Published: June 2021

Previously, we showed that intestinal epithelial cells (IEC) exposed to simulated microgravity display lower transepithelial resistance (TER) and delayed localization of tight junction proteins indicating a barrier defect. Here, we investigated whether simulated microgravity increases susceptibility to epithelial barrier defects by the alcohol metabolite, acetaldehyde. HT‐29 IEC were cultured (i) on microcarrier beads for 18 days in a rotating wall vessel (RWV) to simulate microgravity, (ii) on beads without microgravity (static control), and (iii) in flasks (flask control). After removal of cells from beads or flasks and seeding on semi‐permeable supports for 11 and 14 days, RWV and control IECs were pre‐incubated with phosphate buffered saline (PBS) for 1 hour followed by 0.5% vapor phase acetaldehyde or PBS alone for 5 hours. TER, expressed as % change, was measured following PBS preincubation and again after 5hr treatment. Acetaldehyde caused a greater TER decrease in RWV cells (−13 ± 4.9%; n=6; p<0.05) vs. static (−3 ± 6.9%; n=6) and flask controls (−6 ± 5 %; n=6). PBS alone had no significant effect. Acetaldehyde also increased permeability to 4KD FITC‐dextran in RWV cells vs. controls. ZO‐1 and occludin proteins showed correlative decreases in expression. These data suggest that a simulated microgravity environment increases acetaldehyde‐induced barrier defects. Supported by NIH UH2 AA019708–01.
Role of zonula occludens in reduced epithelial cell proliferation by hypertonic stress
Authors: Qiao Xiaomu , Roth Isabelle , Feraille Eric , Hasler Udo
Published: June 2021

In addition to their role as epithelial barriers, tight junctions (TJs) function as dynamic signaling reservoirs involved in regulating the proliferative potential of epithelial cells. Hypertonic stress reduces cell proliferation and alters cell morphology. Here, we examined whether TJ zonula occludens (ZO) modulate cell proliferation under conditions of chronic hypertonic stress. As revealed by microscopy analysis and FACS, proliferation of spontaneously immortalized renal principal collecting duct (CD) mCCDcl1 cells is strongly dependent on cell confluency when grown under isotonic conditions (300 mOsmol/kg). Low levels of cell proliferation were accompanied by a reduced S phase and increased G0/G1 phase. Real‐Time PCR and Western blot analysis showed that ZO‐3 abundance increased with cell confluency while ZO‐1 and ZO‐2 abundance was unaffected. Confocal microscopy analysis revealed that expression of all three ZO isoforms at the cell surface increased with cell confluency. All observed changes were enhanced in slowly proliferating cells adapted to NaCl‐hypertonic medium (500 mOsmol/kg). Under isotonic conditions, knockdown of ZO‐1 and ZO‐2 by siRNA increased G1 phase, while knockdown of ZO‐3 promoted cell cycle progress. Similar results were obtained in cells habituated to hypertonic medium. These data reveal differential effects between ZO isoforms on renal CD cell proliferation. In addition, they indicate that ZO submembrane recruitment may influence slow cell proliferation under hypertonic conditions.
Sublethal Versus Lethal Hydrogen Peroxide‐Induced Injury To Renal Epithelial Cells: Roles Of Tight Junction Proteins
Authors: Janosevic Danielle , Singh Nancy , Aalami‐Harandi Pegah , Rohring Victoria , Axis Josephine , Amsler Kurt
Published: June 2021

Hydrogen peroxide (H2O2) treatment of renal epithelial cells is a model for renal ischemia‐reperfusion injury. Lethal, but not sublethal H2O2 caused collapse of domes in confluent MDCK cell populations. H2O2 produced a concentration‐dependent increase in paracellular calcein movement across confluent MDCK cell populations. In contrast, TransEpithelial Resistance was only decreased by lethal concentrations of H2O2. The cellular contents of tight junction proteins, occludin, ZO‐1 and ZO‐2, were not altered by treatment with either sublethal or lethal H2O2 concentrations. H2O2 produced a concentration‐dependent decrease in basal F‐actin stress fibers. Sublethal H2O2 did not alter the localization of occludin, ZO‐1 or ZO‐2 but localization was affected modestly by lethal H2O2. Knockdown of either occludin or ZO‐2 increased the sensitivity of MDCK cells to H2O2‐induced injury. In contrast, knockdown of ZO‐1 or overexpression of occludin decreased MDCK cell sensitivity to H2O2. These results indicate that occludin, ZO‐1 and ZO‐2 have different functional roles in mediating the effects of sublethal and lethal H2O2.
Genetic variants in Arhgef11 promote kidney injury and reduced renal function in Dahl S rats
Authors: Jia Zhen , Guo Zibiao , Johnson Ashley C , Garrett Michael R
Published: June 2021

Through positional cloning, genetic variants in Arhgef11, a Rho guanine nucleotide exchange factor, were implicated in kidney injury exhibited by the Dahl salt‐sensitive (S) rat. Kidney injury was associated with increased expression of Arhgef11 and upregulation of Rho‐ROCK pathway. To understand the mechanism by which altered expression and/or protein differences in ARHGEF11 could play a role in kidney injury, stably transduced Arhgef11 knockdown cell lines (lentiviral shRNA) as well as primary cultures of proximal tubule cells (PTC) were studied. Genetic knockdown of Arhgef11 resulted in reduced RhoA activity, decreased activation of Rho‐ROCK pathway (western blot) and less stress fiber formation versus control, similar to what was observed by pharmacological inhibition (fasudil). PTCs from S rats exhibited increased expression of Arhgef11, activation of Rho‐ROCK, and decreased uptake of FITC‐albumin compared to control (minimal congenic). S primary PTCs stimulated with TGFβ1 were more prone (versus control) to epithelial‐mesenchymal transition (EMT) as demonstrated by increased expression of N‐Cadherin, Vimentin, Col1a1 and spindle shape morphology. In summary, these studies suggest that the functional significance of genetic variants in Arhgef11 may be of major importance in kidney injury in the S rat by promoting changes in cell morphology (Rho‐ROCK and/or EMT) and function of tubule cells.
Blueberry treatment improves renal function and reduces oxidative stress in Metabolic Syndrome animals – Role of Toll‐like receptor 4 (TLR4)
Authors: Nair Anand R. , Vila Jorge , Del Piero Fabio , Francis Joseph
Published: June 2021

Metabolic syndrome (MetS) is characterized by a cluster of health factors that indicate a higher risk for cardiac disease, renal disabilities and diabetes. Although inflammation and oxidative stress in renal dysfunction has been well studied, the mechanism by which natural antioxidants protect against MetS is not clear. Blueberries (BB) are among the richest source of antioxidants known to have anti‐inflammatory and antioxidant properties. We hypothesize that BB protect against MetS via inhibition of TLR4, which is an upstream receptor in several inflammatory pathways. Male zucker rats – Lean controls (LZR) and Obese (OZR) were both fed with a BB‐enriched diet or a control diet for 15 weeks. Compared to controls, the rats fed with BB exhibited higher glucose sensitivity, lower blood pressure and improved renal function. Free radical production rates measured by electron paramagnetic spectroscopy (EPR) showed a decreased total reactive oxygen species, superoxide and peroxynitrite levels in BB treated rats. Reduction in renal pathology and improvement in antioxidant levels in the BB‐fed rat kidneys were consistent with the EPR results. BB treated animals also expressed lower gene and protein levels of TLR4 and proinflammatory cytokines. In conclusion, TLR4 inhibition is a mechanism by which blueberries protect against oxidative stress and renal damage, and prevent the onset of MetS. Research supported by NIH.
Shroom3, a novel GWAS renal candidate, is essential for glomerular barrier function
Authors: Yeo Nan Cher , O'Meara Caitlin , Flister Michael , Cliff Michael , Lazar Jozef , Link Brian , Jacob Howard J.
Published: June 2021

Shroom3 is a novel candidate for kidney disease, identified by human genome‐wide association studies (GWAS). We identified 12 coding variants on Shroom3 in the Fawn‐Hooded Hypertensive (FHH) rat, a model of progressive renal failure, and hypothesized that mutations in the FHH Shroom3 impair its function and contribute to renal failure. Pull‐down experiments showed that FHH Shroom3 had a 7‐fold decreased actin‐binding affinity compared to the control (10.0±3.2 vs 67.4±16.2, respectively, p <0.01). In zebrafish, knockdown of Shroom3 by morpholino (MO) increased glomerular permeability, indicated by a decreased 70‐ kDa FITC‐dextran in the circulation at 48 hours after dextran injection (60.3±9.6 vs 103.1±7.3 % dextran in control, p <0.05). Notably, the leaky phenotype induced by MO was completely rescued by the control allele, but not the FHH Shroom3 mRNA, supporting the hypothesis that the FHH Shroom3 allele contributes to renal impairment. We further created a podocyte‐specific Shroom3 knock‐down zebrafish which showed barrier dysfunction and podocyte effacement, suggesting that Shroom3 is important in the regulation of podocyte morphology and function, by regulating cytoskeleton in epithelium. Our results demonstrate for the first time that Shroom3 is essential in maintaining podocyte integrity and regulation of glomerular function across species and further support its role in kidney disease.
Methods for the teaching of gross anatomy: A qualitative look at the use of cadaver dissection, prosection, plastination, and computer‐aided technology as effective methods
Authors: Day Leslie J , Goldberg Maggie , Molloy Elizabeth , Moran Katherine C , Rocco Christa
Published: June 2021

Human dissection as a means of studying human anatomy began 2,300 years ago. In the 20th century new teaching and learning methods of Gross Anatomy such as plastinated models and computer‐aided technology came into practice. This literature review aims to determine which methods are most effective, efficient, and beneficial for promoting student learning of Gross Anatomy. An electronic database search of MEDLINE and Cinahl was conducted. 3 reviewers extracted data and assessed methodologic quality using a standardized process and data form. Discrepancies were resolved using a normative process. Articles were identified that analyzed the use and effectiveness of cadaver dissection, prosection, plastination, and/or computer‐aided technology in the teaching of Gross Anatomy to health science students, specifically Physical Therapy students. The results of the literature review indicated that the concurrent use of multiple methods of teaching was the most efficient and beneficial way to learn Gross Anatomy; that dissections alone were not as effective and efficient as cadaver usage (including dissections or prosections) alongside plastinations and/or computer‐aided technology.
Teaching Oncology Residents Anatomy: A Multidisciplinary (MDT) Approach
Authors: D'souza Leah , Jaswal Jasbir , Johnson Marjorie , Chan Francis , Tay KengYeow , Fung Kevin , Palma David
Published: June 2021

Radiation oncology has undergone a paradigm shift with the advent of precision radiotherapy techniques, demanding a thorough understanding of gross and radiologic anatomy for diagnostic and therapeutic applications. Complex anatomic sites present challenges for learners and are not well‐addressed in traditional postgraduate curricula. We developed a novel, MDT, hands‐on head‐and‐neck curriculum for residents and empirically assessed learning outcomes. 15 post‐graduate trainees participated in 4 MDT head‐and‐neck workshops, created collaboratively by an anatomist, radiologist, radiation oncologist, and otolaryngologist. Pre‐ and posttesting was performed to assess knowledge and accuracy of contouring, with a demographic profile survey and post‐intervention feedback survey. Paired analyses of knowledge pretests and postests were performed by Wilcoxon signed‐rank test. A statistically significant (p<0.001) mean absolute change of 4.6 points was observed between knowledge pretest and posttest scores. Contouring accuracy will be analyzed qualitatively (adequacy assessed by an expert) and quantitatively (calculating spatial overlap of participants’ contours and a gold standard through the dice similarity coefficient). Incorporating MDT anatomic workshops into the curriculum is a beneficial intervention associated with improved post‐intervention scores and resident satisfaction.

Grant Funding Source: Departmental Submitted to PAEA 5/25/2012 (bqmelcher)
Training increases subjects’ fixation time on cognitively salient locations
Authors: Colliard Kitzia , Pfaff Lee , Zumwalt Ann
Published: June 2021

Conventionally, learning is measured by giving students a series of tasks that are later assessed to demonstrate their knowledge or skill acquisition. Our lab is investigating whether learning may be objectively described by using gaze tracking to examine how individuals interact with images before and after training. Subjects in the experimental group are trained to use salient features to identify cell images, which have been assigned a number 1–6. Control subjects receive no training and are shown pictures of the numbered cells. Both groups are then tasked to identify cells by number. We postulate that an educational interaction will increase the amount of time a particular subject fixates on educationally salient regions of the image, also known as areas of interest (AOIs). Preliminary analysis shows discrete labeled and trained educational salient features (for example: attachments in original orientation of oblique 2 [experiment 346.186 +/− 19.288 ms; control 530.196 +/− 79.680 ms] are statistically significant in selected cell stimuli presented. These results do indicate an increase in the amount of time a student fixates on educational AOIs when being explicitly taught what salient areas to fixate on. While we have only completed a small sample size additional subjects are planned. These results are promising indications of the utility of gaze tracking for objectively documenting learning.

Grant Funding Source: Boston University (Internally Funded)
Reflective writing highlights improved student metacognition in an upper level undergraduate anatomy course
Authors: O'Loughlin Valerie Dean , Griffith Lauren Miller
Published: June 2021

Reflective writing (such as minute papers, journaling, or blogs) may help students monitor and self‐regulate their learning throughout the progression of a course. In addition, instructors may assess the development of student metacognition and their understanding of the subject matter through evaluation of this writing.

Previously, the researchers examined how the use of “blogs” (online journals) in an upper level human anatomy course may improve student metacognition in understanding human anatomy. The original sample was small (20 students) but indicated students became more cognizant of their strengths and weaknesses in mastering anatomy as the semester progressed. This current research examines another cohort of students (36 students) in the same undergraduate class. These students reviewed 10 radiology online cases each throughout the semester and then reflected about their understanding of the anatomy, pathology and medical imaging interpretation in online blogs. Researchers scored each line of each blog, using the codebook that was developed from a grounded theory approach.

As with the pilot study, the students in the larger sample also became more confident and assessed their skill in identifying anatomical structure more positively as the semester progressed. Early in the semester, student blogs expressed more anxiety and confusion about the anatomical material, and students tended to rely on guessing to solve the cases. By the end of the semester, guessing was replaced by methodical deduction for solving the cases and students were able to accurately assess their understanding of anatomy. The use of blogs (reflective writing) allowed the researchers to evaluate the improvement in student metacognition using a grounded theory approach.
Focused preparation of anatomy and physiology instructors for the undergraduate college and university setting‐ a report on the first cohort
Authors: Crocker Robert
Published: June 2021

In January of 2011, the New York Chiropractic College, a fully accredited multi‐disciplinary healthcare education institution, introduced a new graduate degree program: Master of Science in Human Anatomy and Physiology Instruction (MSHAPI), offered online to terminal healthcare degree holders and academic biologists teaching, or preparing to teach, anatomy and physiology (A&P) in the undergraduate college and university setting. The MSHAPI program consists of 36 credits, including 18 credits of Human Anatomy & Physiology Instruction, 12 credits of Instructional Theory and Practice, and 6 elective credits. The MSHAPI program leverages the A&P competencies acquired by the candidate in prior educational preparation by combining content expertise with instructional theory and practices. The first cohort graduated in December 2012. This study examines survey data reflecting student demographics, completion rate, and student evaluations of program design, delivery, and effectiveness.
Developing competency in communication: Medical student perceptions of patients’ knowledge of anatomy
Authors: Dudenkov Daniel , Primus Jason , Mayer Susan , Pawlina Wojciech , Lachman Nirusha
Published: June 2021

Effective communication of medical information by doctors to patients has been found to be positively related to patient satisfaction. In the United States ACGME requires doctors in training to meet the competency of effective communication across many socioeconomic and cultural backgrounds. One of the main contributors to ineffective patient communication is inaccurate perception by the doctor about the extent of a patient's medical knowledge. This study seeks to elucidate medical student perceptions of patients’ knowledge of anatomy based on patient age, sex, occupation, education level and race. It also seeks to understand which of these matter most in guiding students’ assumptions. Patients were asked to complete a questionnaire, created in collaboration with the Mayo Clinic Patient Education Center, which included a multiple choice anatomy quiz and demographic information. First year medical students who had just completed their gross anatomy course were given the same anatomy quiz and a survey that included the demographic profiles of the patients. They were then asked to predict how well the patients scored. Student perceptions of patient knowledge were compared to the actual scores. Pending the results of this study, we anticipate that medical students will over‐estimate patients’ anatomical knowledge. This project was funded by the Department of Anatomy, Mayo Clinic, Rochester, MN.
Application of stereoscopic visualization on surgical skill acquisition in novices
Authors: Mistry Manisha , Roach Victoria A , Wilson Timothy D
Published: June 2021

This study examines the influence of monoscopic vs. stereoscopic visualization in novice trainees performing the MISTELS, a validated laparoscopic skill evaluation system consisting of 5 distinct tasks. We hypothesize a difference in performance based on visualization modality. First and second year medical students (n=31) performed the MISTELS battery of tasks using either monoscopic or stereoscopic visualization displays. Regression analysis indicates performance was not correlated to participant manual dexterity or visual spatial ability (p>;0.05). Monoscopic visualization was shown to produce significantly better performance in the peg transfer task alone (p=0.001), with visualization modality producing no significant difference in performance of the remaining tasks (p>;0.05). Qualitatively, 57.1% of participants believed their performance was aided by stereoscopic visualization. Most participants rated the peg transfer task the least difficult task (60%), and the intracorporeal knot‐tying task the most difficult (65.9%). These results suggest the intrinsic difficulty of the MISTELS tasks may exceed a novice user's skill, rendering no benefit with additional 3D cues in naïve surgical trainees, and may serve to increase cognitive load, potentially decrease skill acquisition and learning.

Grant Funding Source: Summer Research Training Program, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, Canada
Stereo Laparoscopy: A Novel Approach to Resident Surgical Education
Authors: Roach Victoria , Mistry Manisha , Wilson Timothy
Published: June 2021

Elevated spatial ability is linked to improved surgical skill acquisition in experienced individuals. This may be important in laparoscopic skill mastery, where stereo visualization may confer an advantage to novices of variant spatial ability. This study aims to evaluate differences in skill acquisition resulting from variable spatial ability in future laparoscopists.

In a pilot study, pre‐clerkship medical students were subdivided into groups based on spatial ability as measured by a Mental Rotations Test (High spatial scores: MRT >;14, Low spatial scores: MRT <10). Students were introduced to tasks via standardized video instruction, and asked to complete four validated laparoscopic tasks under both stereo and monocular viewing paradigms. Students were evaluated on task performance for timing, completion and efficiency.

No significant difference was observed between students of high and low spatial ability for any individual task, overall, or in either viewing modality via ANOVA with repeated measures. A trend of higher overall average scores for High spatial ability students (86.68 ± 15.14) was evident compared to low spatial ability students (76.67 ± 15.73).

This pilot study suggests that stereo visualization benefits individuals differently according to individual spatial ability. We postulate that stereo visualizations may serve to compensate for reduced spatial ability, thus enhancing skill performance in individuals of low spatial ability.

Grant Funding Source: Departmental
Online Histology modules for first‐year medical students: a student to student approach
Authors: Butler Myra V. C. , Yule Heather N , Pinder Karen E
Published: June 2021

Three online training modules to introduce Histology were created by a second‐year medical student to provide a strong foundation for effective and efficient learning in the Histology laboratory. Members of all four medical school classes were surveyed for feedback on the most challenging and confusing concepts in Histology. Based on the results of over one hundred and forty student replies across all years, three online video modules were created: Approaching Histology; Introduction to Slide Preparation and Common Stains; and Introduction to Imagescope (digital slide viewing system). Content ranged from an overview of common stains and slide artifacts to understanding how to extrapolate 3‐ dimensional structures from 2‐dimensional slides. These modules are unique as they were created from the perspective of a fellow student and targeted the most common needs identified by the student‐body survey. This student‐initiated summer project was funded by the University of British Columbia Department of Cellular and Physiological Sciences.

Grant Funding Source: AAA
Anatomical Animation: New Frontiers in Gross Anatomy Instruction.
Authors: Peterson Diana Coomes , Robertson Cynthia
Published: June 2021

One of the struggles of teaching medicine, is accurate visualize of anatomical structures in three dimensions. Although gross dissections and physical models are extremely useful, additional technologies (3D anatomical reconstructions) have developed within the last several years that greatly enhance the ability of students to learn the 3D orientation of anatomy. These 3D programs are currently limited by having the cadaver in a fixed position. We are creating software that enables users to dynamically move anatomical structures in a realistic manner. For this procedure, each anatomical structure is isolated. Movement vectors are programmed to allow relevant movements for each joint and muscle.

Although in its initial stages, we anticipate that anatomy animations will substantially increase the students’ understanding of: 1) the function of individual structures, 2) how individual structures and the forces placed on different structures interact with each other, and 3) how excessive force can alter the health and well‐being of the animal (e.g., fractures, sprains, external force accidents, etc…).

Supported by an ISU CLIM grant.

Grant Funding Source: Iowa State University CLIM grant
Heart Development tutorial – Heart Tube Folding
Authors: DeLorenzo Tami Michelle , Zumwalt Ann
Published: June 2021

Heart tube folding is one of the most critical events of the developmental period, yet for many students, visualizing the anatomy of heart development is difficult and can create many issues and misconceptions. This project describes a workshop that was designed to magnify the process into a larger than life 3‐D hands on model. The 1–1.5 hour workshop reviews the overall heart development in a pre‐quiz and discussion session, then proceeds into an active learning session in which the students create and mold the developing heart tube and heart folding using clay. Using this hands on approach, the students get to create the process of heart folding, which creates a lasting educational experience that can be used as a building block to even more topics in heart development. A clay‐mation video that supplements this exercise was created to allow large groups to visualize the folding action as well will also be demonstrated.

Grant Funding Source: N/A
Augmenting the learning of anatomy beyond the traditional laboratory experience through service teaching of elementary school students: A Medical Student Perspective
Authors: Lee Heajung , Ojukwu Kene , Diaz Molly , Padilla Jessica , Thang Christine , Wisco Jonathan J
Published: June 2021

Anatomy Academy (AA) is a novel project aimed at providing elementary school students a unique learning experience of the human body while nurturing their scientific curiosity in small group sessions. Each organ system‐based session was led by a pair of medical and undergraduate students who led interactive discussions using anatomy organ models and hands‐on activities to present applicable scientific concepts. For medical students, this provided a unique opportunity to demonstrate and deliver anatomy and physiology concepts learned through lecture and laboratory in the pre‐clinical medical school curriculum. In contrast to the passive, memory‐based education acquired from lectures and textbooks, teaching served as an effective resource for active learning that was reliant on deeper, intelligent understanding and creativity. As future physicians, medical students also benefitted from acquiring skills necessary to lead successful teams and communicate effectively with individuals of a broader range of educational backgrounds. Both mentors and mentees benefitted from AA.

Grant Funding Source: The Albert Schweitzer Fellowship and the UCLA Monica Salinas Fellowship
Evaluation of Student Participation and Perceptions of a Neuroscience Community Outreach Project
Authors: Neal Jasmine , Puder Barb
Published: June 2021

Students enrolled in Health Science fields often lack the ability to communicate and educate relevant health care information to patients even though they may be quite proficient on written exams regarding health sciences. To address this potential deficit, students enrolled in the California School of Podiatric Medicine's (CSPM) neuroscience course designed neuroscience posters and interactive neuroscience activities to present to attendees of a Saturday educational brain fair entitled “Get to Know Your Brain!” This educational activity reinforces the neuroscience subject matter, and provides students with an opportunity to enhance communication skills and interaction with various age groups. To measure the impact and effectiveness of this brain event on the student presenters, a survey using the Likert scale was administered to CSPM students to receive feedback on their perceptions of working in a small group, designing age appropriate educational materials, and communicating and educating attendees. Research supported by: The Scott Beamer Memorial Community Service Award

Grant Funding Source: Scott Beamer Memorial Community Service Award
Analysis of overlapping phenotypes from trisomic and euploid embryos of a Down syndrome mouse model (Ts65Dn): implications for human medicine
Authors: Bhatia Naina , Diogo Rui , Roper Randall
Published: June 2021

Down syndrome (DS), i.e. trisomy of Hsa21, exhibits nearly 80 clinically defined traits with varying phenotypic severity. Recent understanding of the genetic basis of DS phenotype has come through the use of mouse models of DS. The trisomic Ts65Dn chromosome seems to be inherited in a Mendelian ration but both trisomic and euploid offspring are lost in pre and postnatal stages and at weaning the frequency of trisomy is significantly lower than Mendelian ratio. The phenotytpic variability of euploid and trisomic embryos has not been analyzed in detail. Our current study suggests that euploid and trisomic mice embryos from a trisomic mother share some common adverse phenotypes in mouse: we investigated phenotypic variability in embryonic day 13.5 offspring from Ts65Dn mice and the euploid embryos reveal a milder version of the trisomic phenotype, but we detected anomalies in cardiac, pharyngeal as well as in neural features along with some specific malformations in embryonic liver as well as developing pituitary in trisomic as well as euploid embryos. Unfortunately there are no detailed published accounts about fine‐tuned analyses of developmental delay, intellectual impairment, muscle hypotonia and other phenotypic anomalies in human euploids born from trisomic mothers; our study therefore provides new insight in this arena and paves the way for future studies on this complex, crucial, and understudied aspect of DS.

Grant Funding Source: N/A