bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased Oxidation From Glucose Limiting Conditions or SOD Deletions Result in Activation of No‐Go Decay and Subsequent P‐body Assembly
Authors: Segal Scott , Cianflone Emily , Jorgensen Anna , McManus Gretchen , Rolin Kyle 
Published: May 2022

The budding yeast, Saccharomyces cerevisiaepreferentially metabolizes glucose anaerobically when it is abundant. However, as glucose becomes depleted, yeast will enter diauxic shift. Under this condition, growth will slow, and glucose becomes metabolized aerobically. Upregulation of aerobic glucose metabolism ultimately leads to the increase of intracellular reactive oxygen species (ROS). The increase of ROS can lead to oxidation of nucleic acids through formation of 8‐oxoguanine bases (8‐oxoG). In mRNA the presence of 8‐oxoG can elicit ribosome stalls, resulting in translational shutdown and the activation of the no‐go mRNA quality control pathway. No‐go decay is mediated by the proteins Hbs1p and Dom34p, which act to remove stalled ribosomes, and will promote cleavage of the mRNA at the stall site. The remaining 5’ fragment is subject to 3’‐5’ decay by the cytoplasmic exosome, while the 3’ fragment is degraded 5’‐3’ by exonuclease Xrn1p in P‐bodies, which are sites of mRNA degradation.Upon growing yeast into diauxic shift, an increase in P‐body assembly was observed. P‐bodies contain mRNA decay enzymes and are sites where nontranslating mRNA will localize to be degraded. This observed increase in P‐body assembly appears to be due to an upregulation of no‐go Decay, as P‐body assembly is reduced in strains lacking either Dom34p or Hbs1p. Upon exposure to the antioxidant quercetin during diauxic shift, P‐body assembly is abrogated showing that generation of ROS is responsible for the activation of no‐go decay and subsequent P‐body assembly. The same result is phenocopied by exposing yeast to glucose limiting conditions (0.5% glucose). As expected with the increased oxidation from glucose limiting conditions, global translation is also reduced. Interestingly, strains lacking either Sod1p or Sod2p, also show a reduction in global translation, along with an upregulation of no‐go decay and P‐body assembly. These data suggest that physiological stresses that lead to an increase in ROS, which can damage mRNA leading to activation of No‐Go Decay and subsequent P‐body assembly.
Gut It Out: An Anatomy Card Game and Study Tool for Medical Students
Authors: Stiver Mikaela L. , Ding Linda , Lalande Alexia , Lau Cat , Lin Winnie , Fejtek Monica , Jeon Sean , Leavitt Sarah , Krebs Claudia 
Published: May 2022

Gamification in medical education involves integrating game principles—including mechanics, design, or experiences—into a learning context. Game‐based approaches in higher education have been shown to improve student engagement, motivation, and performance when applied effectively. Many medical students report feeling overwhelmed by the complexity and content‐heavy nature of anatomy, making it an ideal subject for gamification. In this project, we developed and designed an educational anatomy card game intended for medical students.Students in the inaugural cohort of the Certificate in Biomedical Visualization and Communication (BMVC) at the University of British Columbia teamed up with the Hackspace for Immersive Virtual Experiences (HIVE) and faculty advisors for their capstone project. The team collected survey responses from current medical students to determine desirable game features and dynamics, followed by several rounds of prototyping and piloting. The students also enlisted the help of a subject matter expert in game design.The final card game, entitled “Gut it Out”, is appropriate for players possessing any level of anatomy knowledge, with optional mechanics designed for medical students. Gameplay involves players competing to build fully innervated and vascularized organs. Organ cards specify the number of blood vessel cards (arteries and veins) and nerve cards (somatic, sympathetic, and parasympathetic) required for completion. Additional clinical cards can be played to gain advantages or sabotage opponents. An optional gameplay component challenges players to name each blood vessel and nerve associated with the organs they have completed in exchange for double points. Aesthetics feature a high‐contrast colour palette and bold, simple organ illustrations. The team developed multiple versions of the rules that are currently being play tested by medical students and anatomists. Future directions include incorporating an interactive augmented reality component to enrich the educational value of the organ cards and conducting a mixed methods study to assess the efficacy of the game as a study tool.“Gut it Out” applies gamification to anatomy education to create a fun and educational card game featuring accessible, fast‐paced gameplay. This game was designed to complement and expand the current ecosystem of anatomy resources hosted by the HIVE.
Identification of a Novel Amino Acid Motif Responsible for Peptide Aggregation in vitro.
Authors: Torres Daniel J. , Nyman Karl , Glinka Tomasz , Borysov Sergiy I. 
Published: May 2022

Peptides and their derivatives comprise a substantial sector of drug development initiatives due to their specific biological activities and broad chemical versatility. Among the challenges of peptide drug development is a reduction in peptide solubility that leads to peptide aggregation. This dramatically reduces a peptide’s biological availability and prevents its further testing in vivo.Here we report a physicochemical analysis of peptides that inhibit the CMG helicase, the main replicative helicase within the cell. We demonstrate that the inhibitory peptides had a pronounced propensity to form aggregates in vitro by utilizing light microscopy and a fluorescence‐based peptide aggregation assay. By applying a peptide chase approach and abovementioned testing assays, we identified a short amino acid motif of X‐Leu‐Met‐Leu‐X that was responsible for peptide aggregation. Amino acid substitutions at these key residues were studied to confirm their contribution towards aggregation. Interestingly, substitution of either Leucine residues with Serine residues dramatically increased peptide solubility.
The Effect of Sulindac on Senescence in RPE Cells: Role of cell protective mechanisms Against Oxidative Damage
Authors: Manoharan Samuel P. , Weissbach Herbert P. , Allani Shailaja 
Published: May 2022

Age‐related macular degeneration (AMD) is the leading cause of blindness in industrialized countries. One of the potential contributors to AMD pathology is retinal pigment epithelial (RPE) cell senescence. Through experimental trial, it is shown that sulindac, an FDA approved non‐steroidal anti‐inflammatory drug, protects normal cells such as retinal, cardiac, and neuronal cells against oxidative damage through a preconditioning mechanism. The hypothesis is that sulindac can mitigate RPE cell senescence because of its cellular protective properties. To test this, in vitro, an RPE senescence model was established using tert‐butyl hydrogen peroxide (TBHP) as an oxidizing agent. The cells were treated with TBHP for 12 hours followed by further incubation for four days. Senescence cells were identified using a Beta‐galactosidase assay. The effect of sulindac on senescence was determined by pre‐treating cells with varying concentrations of sulindac for 24 h prior to TBHP treatment.Treatment with TBHP induces senescence in the RPE cells under the conditions used. The Preliminary data shows that there was a reduced number of senescent cells in the samples treated with sulindac compared to the control groups. These findings indicate that oxidative damage induces cell senescence, and sulindac can lower the amount of senescence by protecting the RPE cells from oxidative damage. To summarize, the results suggest that sulindac can be used as a therapeutic agent targeting senescence induced by oxidative damage.
Effect of Hyperinsulinemia on Cerebral Autoregulation and Myogenic Control of Cerebral Blood Flow in Healthy Young Adults
Authors: Shariffi Brian , Lloyd Iman N. , Wagner Jadee , Harper Jennifer L. , McMillan Neil J. , Smith James A. , Manrique‐Acevedo Camila , Padilla Jaume , Limberg Jacqueline K. 
Published: May 2022

ObjectiveHyperinsulinemia has marked vasodilatory effects within the skeletal muscle vasculature in healthy young adults; however, the magnitude of insulin‐stimulated cerebrovascular vasodilation is less clear. Differences between circulations may be due to a greater importance of the cerebral circulation to maintain a constant level of blood flow (i.e., cerebral autoregulation) during hyperinsulinemia. We hypothesized cerebral autoregulation would increase during hyperinsulinemia. Autoregulatory mechanisms, such as myogenic control, play important roles in mediating cerebral vasomotor responses. Thus, we further sought to examine the contribution of the myogenic mechanism to the control of cerebral blood flow during hyperinsulinemia.MethodsMiddle cerebral artery blood velocity (MCAv) and femoral artery blood velocity (FAV) were measured with Doppler ultrasound and femoral artery blood flow (FBF) was calculated in 17 healthy adults (11M/6F, 28±2 yrs, 24±1 kg/m2) at baseline and following a hyperinsulinemic (40 mU/m2body surface area/min), euglycemic infusion. Finger plethysmography was used to assess mean blood pressure (MBP). Normalized transfer function gain between changes in MBP and MCAv were estimated in the 0.02‐0.07 Hz (very low frequency, VLF) and 0.07–0.20 Hz (low frequency, LF) ranges using the Welch method. Interactions between MBP and MCAv or FAV were determined using cross‐correlation analyses.ResultsIntravenous insulin infusion increased plasma insulin concentrations (6±1 to 50±3 μIU/mL, p<0.01) with blood glucose maintained at baseline levels (p=0.33). There was a significant increase in FBF (121±15 to 151±19 mL/min, p=0.03) during hyperinsulinemia, with no change in MCAv (61±4 to 59±4 cm/s, p=0.28) or MBP (86±2 to 89±2 mmHg, p=0.10). There was no effect of hyperinsulinemia on normalized transfer function gain in the VLF (p=0.25) or LF ranges (p=0.46). Hyperinsulinemia had no effect on the association between MBP and MCAv (p=0.15) or FAV (p=0.82).ConclusionsHyperinsulinemia in healthy young adults elicits peripheral vasodilation, but no change in MCAv. Contrary to our hypothesis, the sensitivity of the cerebrovascular circulation to changes in MBP (i.e., cerebral autoregulation) is not altered during systemic hyperinsulinemia in healthy adults. Furthermore, the contribution of the myogenic mechanism to the control of blood flow in the peripheral and cerebral circulations is unaffected by hyperinsulinemia. Whether these results translate to disease states (e.g., diabetes) and the implications for cerebrovascular health warrant further exploration.
Hyperoxia‐Induced Preretinal Membrane Formation and Retinal Detachment in the Mouse
Authors: Diaz Gabriela M. , Heck Madison , Cuff Evan , Martin Mark , Guthridge Bryanna , Lee Tyler , Penev Boris , Gerhart Jacquelyn , George‐Weinstein Mindy , Bravo‐Nuevo Arturo 
Published: May 2022

BackgroundRetinal detachment (RD) is a vision‐threatening consequence of several conditions including retinopathy of prematurity (ROP). Numerous studies have established the connection of high oxygen concentration altering retinal development in preterm infants, leading to RD and blindness in later stages. The goal of this study was to develop a reproducible, non‐invasive model mouse of human ROP that could be used to study the cellular events leading to the formation of tractional preretinal membranes and RD.HypothesisPlacing C57BL/6J mice in hyperoxic conditions for one week starting at birth will induce a non‐traumatic sequence of retinopathy leading to tractional RD that mimics the pathophysiology of detachment seen in ROP.MethodsC57BL/6J newborn mice were placed into a hyperoxic environment (65% oxygen saturation) for 7 days then reared in ambient air. Retinas were observed at weeks 4, 5, and 7 via spectral‐domain optical coherence tomography (OCT). Eyes were processed for histology and immunostaining for the myofibroblast marker alpha‐smooth muscle actin (α‐SMA).ResultsFour weeks after birth, 100% of mice placed in hyperoxia exhibited retinal blebs, 91% had developed preretinal membranes, and 9% had RD. At 5 weeks, 100% and 27% had preretinal membranes and RD, respectively. At week 7, the number of mice with RD increased to 33%. Preretinal membranes arose at the surface of the retina above the optic nerve head. RD occurred between the neurosensory retina and the underlying retinal pigment epithelium. Myofibroblasts were detected with the antibody to α‐SMA in the preretinal membranes and above areas of RD.ConclusionThe hyperoxia‐induced retinopathy model was confirmed to induce retinal pathology in newborn mouse pups. Retinal pathology progressed during a 7‐week time period (i.e. retinal blebs to preretinal membranes and folds to retinal detachment). This noninvasive model replicates the oxygen‐induced retinopathy seen in human ROP. The model is useful for investigating the origin of cells that contribute to the formation of tractional retinopathy, especially PRMs and RD. The presence of α‐SMA‐positive cells overlying areas of retinopathy suggests the contractile property of myofibroblasts induces tractional RD.
Uncovering Anti‐Arrhythmic Potential of Stellate Ganglion Purinergic Receptors
Authors: Bussey Carol T. , Davis Harvey , Bogert Emma , Paterson David J. , Paton Julian F. 
Published: May 2022

Cardiovascular disease affects over 30% of people worldwide and is one of the leading causes of death each year. Elevated sympathetic nerve activity is a common feature of cardiovascular disease, contributing to end‐organ damage, morbidity and mortality. Recent findings indicate that short‐circuiting sympathetic nerve overactivity by removal of the stellate ganglion can eradicate arrhythmias, emphasising the need for novel therapeutic targets to correct signalling non‐invasively.We have revealed upregulation of the P2X3 purinergic receptor in stellate ganglia of Spontaneously Hypertensive (SHR) compared to Wistar rats (16 week‐old), via RNASeq transcriptional profiling. We hypothesise that these purinergic receptors within cardiac stellate ganglia play a role in the excessive sympathetic drive to the heart in cardiovascular disease and can initiate cardiac arrhythmias. Thus, we have investigated the functional role of purinergic receptors in the stellate ganglion.Administration of ATP to acutely isolated post‐ganglionic sympathetic neurones from the stellate ganglia of Wistar rats (4‐6 week‐old) evokes a significant increase (Median; 0.21) in [Ca2+]i as measured by Fura‐2AM imaging (n=15, Wilcoxon matched‐pairs test; p<0.0001). This ATP‐induced calcium transient was inhibited by specific P2X3 receptor antagonism with either NF‐10 or AF‐130.Cardiac effects of stellate ganglion purinergic stimulation were investigated in the working heart‐brainstem preparation of Wistar rats (4‐6 week‐old). Increasing doses of ATP (50‐250 µg) delivered via microinjection (50‐250 µL) directly to the right stellate ganglion produced either a tachycardia (18 ± 6 bpm, n=6) or bradycardia (‐24 ± 12 bpm, n=5); these responses were typically found at distinct sites within the ganglion. Preliminary data from SHR suggest that higher doses of ATP (≥250µg) may be arrhythmogenic (n=3).P2X3 purinergic receptors are present in the sympathetic stellate ganglion and contribute to calcium ion flux and cardiac chronotropic regulation. Overexpression of P2X3 receptors is likely to contribute to excessive cardiac sympathetic activity and the development of hypertension and cardiac arrhythmias, making them a promising novel therapeutic target.
Teaching Reproductive Anatomy through Abdominal Hysterectomy on a Cadaver
Authors: Fogarthy Tannice , Richter Emily , Ravikumaran Nair Rakesh 
Published: May 2022

IntroductionMedical journals have stated there is a decrease in anatomical knowledge amongst medical students which then hinders their knowledge of pathologic processes. Performing a hysterectomy requires knowledge of the uterine structures and the ability to properly identify them. Performing a hysterectomy would allow for 4th year medical students interested in the field of obstetrics and gynecology to learn these structures as well as learn the steps of a hysterectomy prior to residency.ObjectiveTo perform an abdominal hysterectomy as a means to enhance pelvic anatomical knowledge and introduce 4th year medical students to the operative technique.Material and MethodsTwo fourth year medical students at HWCOM (CO2022) participated. The abdomen was opened, and its contents retracted to obtain access to the genitourinary structures. The round ligament was ligated and divided opening the retroperitoneal space. The utero‐ovarian ligament was then clamped, divided and ligated. The ovary was left attached to the infundibulopelvic ligament. The same steps were repeated on the opposite side. The anterior vaginal wall was then exposed by dissecting the bladder off the anterior wall of the lower uterine segment and cervix. The uterine vessels were skeletonized bilaterally at the lower uterine segment then clamped and ligated. The remaining parts of the broad ligament was then clamped, divided and ligated to the cervix. The broad ligament was then detached from the lateral cervix further exposing the upper vagina. The vagina was then divided below the cervix with a scalpel, and the uterus and cervix were then removed. The vaginal apex was then closed with a figure of 8 stitch.Results/ImagesThere were 8 main steps as illustrated by the pictures in the appendix for visual aid and future instruction of medical students.Conclusion and Significance/ImplicationPerforming a hysterectomy on a cadaver required knowledge of uterine anatomy, its surrounding structures and the steps of a hysterectomy. This can be a method to teach medical students uterine anatomy. Future implications of this practice on students first live hysterectomy are yet to be explored but worthwhile as a future study.
Nearest Neighbor Density Analysis of the Stellate Ganglia
Authors: Yang Ronald , Fefferman Ann , Tse Shiaomeng , Park Danny , Wisco Jonathan J. 
Published: May 2022

IntroductionThe so‐called heart‐brain axis is the neurological and physiological connection between the autonomic systems of both organs. The stellate ganglia and superior cervical ganglia are the location of the sympathetic neuronal cells that innervate the vasculature of the heart and brain, respectively. The paravertebral chain connects the ganglia on either side of the neck. Myocardial infarction is thought to cause remodeling of the sympathetic neurons in the stellate ganglia. In a recent qualitative study, the stellate ganglia were shown to remodel with regard to cell body number, size, density, and clustering in the presence of various cardiac diseases. We developed a tool to automatically quantify the nearest neighbor density of neurons weighted by size in pathology specimens of the stellate ganglia. This is the first step to quantifying sympathetic nervous system changes in the heart‐brain axis of cardiovascular pathology.MethodsBiopsies of the stellate ganglia were collected bilaterally from an opportunity sample of 17 willed body donors (34 total specimens) with and without histories of self‐reported myocardial infarction (MI) and/or cerebrovascular accident (CVA). The ganglia were stained with luxol fast blue and cresyl violet which allowed for histological analysis of local neurons. Images of the ganglia at its middle coronal slice after staining were processed using multiple libraries in python, primarily PIL and OpenCV. The images first underwent multiple filters: a high contrast filter and a smoothing filter. After this filter, the image passed through a color threshold that obtained the location of each neuron; the locations of each neuron were used to make a binary image. The binary image was passed through various parameters such as neuron area, radius of the minimum enclosing circle, and a ratio of the area of the neuron and area of the minimum enclosing circle. A heatmap was generated from this last image through a convolution calculation that takes into account the location of the neuron, size, and proximity of surrounding neurons‐ all variables that are needed to calculate nearest neighbor density. Quantitative and qualitative measurements are generated from this: a graphical map of high and low density areas and number of neurons per given threshold of density.ResultsA pipeline was created that generates heatmaps of the nearest neighbor density based on the location and size of neurons on the stellate ganglia. Quantitative data is also measured based on how many neurons are located in varying levels of density structures.ConclusionsHeatmaps of the nearest neighbor density and size of the neurons potentially show signs of cardiac diseases‐ regions of high density or patterns of where highly dense regions are located are indicators. Developments within computation pathology is an easily accessible and pioneering way for new technological innovation.
Intracranial Cerebrovascular Reactivity by Traditional and Novel Methods in Young, Middle, and Old Aged Healthy Males and Females
Authors: Koep Jodie L. , Coombes Jeff S. , Barker Alan R. , Taylor Chloe E. , Pizzey Faith K. , Ruediger Stefanie L. , Bond Bert , Bailey Tom G. 
Published: May 2022

ObjectiveLower cerebrovascular reactivity (CVR) to hypercapnia is associated with increased risk of age‐related cognitive decline and all‐cause mortality. Despite the important clinical implications of CVR, evidence of the physiological changes across the healthy adult lifespan is conflicting, with limited findings in females. The aim of this study was to assess the effect of age and sex on CVR. We hypothesized: 1) CVR to be lower in middle‐aged and older compared to young adults, and 2) a higher CVR in young females compared with young males, and a higher CVR in older males than older females.MethodsYoung (n=25, 12 female, age 27±1.5y), middle‐age (n=31, 18 female, age 54±7.3y) and older healthy participants (n=20, 10 female, age 70±2.5y) completed CVR via inhalation of 5% carbon dioxide (CO2) for 5 minutes. Traditional CVR was characterized by the peak middle cerebral artery velocity (MCAv) response per mmHg increase in end‐tidal CO2 (traditional cm/s‐1mmHg), and using a novel mono‐exponential model to characterize the dynamic onset response of the MCAv. Independent samples ANOVA was used to compare main and interaction effects of age and sex.ResultsTraditional CVR was not different between young, middle and older groups (2.0±0.7 vs 1.8±0.9 vs 1.9±0.9 cm/s‐1mmHg; P=0.102). Dynamic onset (novel) responses revealed the time constant of the MCAv response was significantly slower in older and middle‐aged compared to young adults (29±16 vs 27±20 vs 14±9 seconds, P=0.03). No effects of sex were observed for traditional or novel CVR (P≥0.14), but young females had a higher baseline MCAv than young males (70.8 vs 78.6 cm/s‐1P=0.04), which was not observed in middle and older age adults.ConclusionsCVR is preserved in ageing adults, but the speed of the MCAv response is blunted in older and middle‐aged adults compared to young adults. Utilizing dynamic onset responses reveal underlying differences in cerebral regulation with healthy ageing that were not detected by traditional methods.