Cell and Developmental Biology Commons^™

Structured Diet And Exercise Guidance In Pregnancy To Improve Health In Women And Their Offspring: Study Protocol For The Be Healthy In Pregnancy (Bhip) Randomized Controlled Trial, Maude Perreault, Stephanie A. Atkinson, Michelle F. Mottola, Stuart M. Phillips, Keyna Bracken, Eileen K. Hutton, Feng Xie, David Meyre, Rita E. Morassut, Harry Prapavessis, Lehana Thabane

Anatomy and Cell Biology Publications

BackgroundEvidence from epidemiological and animal studies support the concept of programming fetal, neonatal, and adult health in response to in utero exposures such as maternal obesity and lifestyle variables. Excess gestational weight gain (GWG), maternal physical activity, and sub-optimal and excess nutrition during pregnancy may program the offspring's risk of obesity. Maternal intake of dairy foods rich in high-quality proteins, calcium, and vitamin D may influence later bone health status. Current clinical practice guidelines for managing GWG are not founded on randomized trials and lack specific active intervention ingredients. The Be Healthy in Pregnancy (BHIP) study is a randomized controlled …

Functional Outcomes In Early (T1/T2) Supraglottic Cancer: A Systematic Review, Benjamin Van Der Woerd, Krupal B. Patel, Anthony C. Nichols, Kevin Fung, John Yoo, Danielle S. Macneil

Anatomy and Cell Biology Publications

ObjectivesOrgan preserving surgery (OPS) and radiotherapy (RT) are both accepted treatment options for early stage supraglottic cancer (SGC). Radiation has supplanted surgery in most cases, because of the perception that surgery results in poorer functional outcomes. However, evidence suggests that OPS with a neck dissection may be associated with improved survival. Our objective was to conduct a systematic review of the literature to compare functional outcomes of OPS and RT for early SGC.MethodsWe searched Medline, EMBASE and Cochrane Central Register of Controlled Trials to identify studies. Studies were included if they reported functional outcomes on 10 or more patients with …

Survival Of Patients With Subglottic Squamous Cell Carcinoma, S D. Macneil, K Patel, K Liu, S Shariff, J Yoo, A Nichols, K Fung, A X Garg

Anatomy and Cell Biology Publications

Objective: Subglottic squamous cell carcinoma is a rare subsite of laryngeal cancer that behaves more aggressively and portends a worse prognosis. Using a population-based cancer registry, our objective was to report overall survival (OS) and laryngectomy-free survival (LFS) in patients diagnosed with subglottic squamous cell carcinoma, and to determine whether primary laryngectomy results in improved survival.

Methods: This retrospective population-based study considered patients with a new diagnosis of squamous cell carcinoma in the province of Ontario over a 15-year period (1995-2009). The Ontario Cancer Registry was examined for patients with the diagnosis of interest during the period …

Hdl In Endocrine Carcinomas: Biomarker, Drug Carrier, And Potential Therapeutic, Emily E. Morin, Xiang-An Li, Anna Schwendeman

Physiology Faculty Publications

High-density lipoprotein (HDL) have long been studied for their protective role against cardiovascular diseases, however recently relationship between HDL and cancer came into focus. Several epidemiological studies have shown an inverse correlation between HDL-cholesterol (HDL-C) and cancer risk, and some have even implied that HDL-C can be used as a predictive measure for survival prognosis in for specific sub-population of certain types of cancer. HDL itself is an endogenous nanoparticle capable of removing excess cholesterol from the periphery and returning it to the liver for excretion. One of the main receptors for HDL, scavenger receptor type B-I (SR-BI), is highly …

Waardenburg Syndrome And Left Persistent Superior Vena Cava, Driss Raissi, Alexander Christie, Kimberly Applegate

Radiology Faculty Publications

Waardenburg syndrome (WS) is a rare genetic disorder secondary to neural crest cell developmental abnormalities. It is predominantly described as an auditory-pigmentary syndrome with diverse patient presentation, typically involving congenital sensorineural hearing loss and pigmentation abnormalities of the skin, hair, and iris. Other developmental abnormalities that may be associated with this syndrome are Hirschsprung's disease and a myriad of cardiovascular congenital defects. We present a case of a young girl with WS who found to have a persistent left superior vena cava (PLSVC) draining into the coronary sinus. The prevalence of PLSVC is increased in patients with chromosomal and genetic …

Lestaurtinib Is A Potent Inhibitor Of Anaplastic Thyroid Cancer Cell Line Models, Nicole Pinto, Stephenie D. Prokopec, Frederick Vizeacoumar, Karlee Searle, Matthew Lowerison, Kara M. Ruicci, John Yoo, Kevin Fung, Danielle Macneil, Jim C. Lacefield, Hon S. Leong, Joe S. Mymryk, John W. Barrett, Alessandro Datti, Paul C. Boutros, Anthony C. Nichols

Anatomy and Cell Biology Publications

Anaplastic thyroid cancer (ATC) is a rare and lethal human malignancy with no known effective therapies in the majority of cases. Despite the use of conventional treatments such as chemotherapy, radiation and surgical resection, this disease remains almost universally fatal. In the present study, we identified the JAK2 inhibitor Lestaurtinib as a potent compound when testing against 13 ATC cell lines. Lestaurtinib demonstrated a potent antiproliferative effect in vitro at nanomolar concentrations. Furthermore, Lestaurtinib impeded cell migration and the ability to form colonies from single cells using scratch-wound and colony formation assays, respectively. Flow cytometry was used for cell cycle …

Cell Specific Control Of The Pallidostriatal Pathway, Shubha Verma '19

Student Publications & Research

Parkinson’s Disease is a neurodegenerative disorder of the basal ganglia. The main cause for Parkinson’s Disease is the depletion of dopamine, a neurotransmitter. The basal ganglia contains four major nuclei: the substantia nigra, the subthalamic nucleus, the external globus pallidus, and the striatum. These nuclei communicate with each other by the use of neurons.

Improving Online Interactions: Lessons From An Online Anatomy Course With A Laboratory For Undergraduate Students, Stephanie M. Attardi, Michele L. Barbeau, Kem A. Rogers

Anatomy and Cell Biology Publications

An online section of a face-to-face (F2F) undergraduate (bachelor's level) anatomy course with a prosection laboratory was offered in 2013-2014. Lectures for F2F students (353) were broadcast to online students (138) using Blackboard Collaborate (BBC) virtual classroom. Online laboratories were offered using BBC and three-dimensional (3D) anatomical computer models. This iteration of the course was modified from the previous year to improve online student-teacher and student-student interactions. Students were divided into laboratory groups that rotated through virtual breakout rooms, giving them the opportunity to interact with three instructors. The objectives were to assess student performance outcomes, perceptions of student-teacher and …

Response To The Growing Dementia Burden Must Be Broader, Werner Hacke, Vladimir Hachinski

Anatomy and Cell Biology Publications

No abstract provided.

Transplantation Of Pediatric Renal Allografts From Donors Less Than 10 Kg, Nickolas Mitrou, Shahid Aquil, Marie Dion, Vivian Mcalister, Alp Sener, Patrick P. Luke

Anatomy and Cell Biology Publications

Few transplant programs use kidneys from donors with body weight (BW) BW < 10 kg would provide similar transplant outcomes to larger grafts. All pediatric en bloc renal transplants performed at our center between 2001 and 2017 were reviewed (N = 28). Data were stratified by smaller (donor BW < 10 kg; n = 11) or larger donors (BW > 10 kg; n = 17). Renal volume was assessed during follow-up with ultrasound. Demographic characteristics were similar between the 2 groups of recipients. After mean follow-up of 44 months (smaller donors) and 124 months (larger donors), graft and patient outcomes were similar between groups. Serum creatinine at 1, 3, and 5 years was no different between groups. At 1 day posttransplant, mean total renal volume in the smaller donors was 28 +/- 9 mm(3) vs 45 +/- 12 mm(3) (P < .01). By 3 weeks, it was 53 +/- 19 mm(3) (smaller donors) versus 73 +/- 19 mm(3) (larger donors) (P = NS). Complication rates were similar between both groups with 1 case of venous thrombosis in the smaller group. With experience, outcomes are equivalent to those from larger pediatric donors.

Fast And Slow-Twitching Muscles Are Differentially Affected By Reduced Cholinergic Transmission In Mice Deficient For Vacht: A Mouse Model For Congenital Myasthenia, Matheus P.S. Magalhaes-Gomes, Marco A.M. Prado

Anatomy and Cell Biology Publications

Congenital myasthenic syndromes (CMS) result from reduced cholinergic transmission at neuromuscular junctions (NMJs). While the etiology of CMS varies, the disease is characterized by muscle weakness. To date, it remains unknown if CMS causes long-term and irreversible changes to skeletal muscles. In this study, we examined skeletal muscles in a mouse line with reduced expression of Vesicular Acetylcholine Transporter (VAChT, mouse line herein called VAChT-KDHOM). We examined this mouse line for several reasons. First, VAChT plays a central function in loading acetylcholine (ACh) into synaptic vesicles and releasing it at NMJs, in addition to other cholinergic nerve endings. Second, loss …

Pannexin 1 Regulates Adipose Stromal Cell Differentiation And Fat Accumulation, Vanessa R. Lee, Kevin J. Barr, John J. Kelly, Danielle Johnston, Cody F.C. Brown, Kevin P. Robb, Samar Sayedyahossein, Kenneth Huang, Robert Gros, Lauren E. Flynn, Silvia Penuela

Anatomy and Cell Biology Publications

Pannexin 1 (Panx1) is a channel-forming glycoprotein important in paracrine signaling and cellular development. In this study, we discovered that mice globally lacking Panx1 (KO) have significantly greater total fat mass and reduced lean mass compared to wild type (WT) mice under a normal diet. Despite having higher fat content, Panx1 KO mice on a high fat diet exhibited no differences in weight gain and blood markers of obesity as compared to WT controls, except for an increase in glucose and insulin levels. However, metabolic cage data revealed that these Panx1 KO mice display significantly increased activity levels, higher ambulatory …

First Canadian Experience With Robotic Laparoendoscopic Single-Site Vs. Standard Laparoscopic Living-Donor Nephrectomy: A Prospective Comparative Study, Patrick P Luke, Shahid Aquil, Bijad Alharbi, Hemant Sharma, Alp Sener

Anatomy and Cell Biology Publications

INTRODUCTION: We aimed to compare the outcomes of robotic laparoendoscopic single-site living donor nephrectomy (R-LESS LDN) vs. standard laparoscopic living donor nephrectomy (LLDN).

METHODS: Between October 2013 and November 2015, 39 patients were allocated to either standard LLDN (n=25) or R-LESS LDN (n=14). Patient demographics, perioperative outcomes, analgesic requirement, visual analogue scale of pain at postoperative days 1, 3, 7, and 30, and a health-related quality of life and body image questionnaire were prospectively collected.

RESULTS: There were no significant differences in demographics and intraoperative outcomes between the two cohorts. The R-LESS LDN cohort had lower analgesic requirement (p=0.002) and …

The Role Of Cholinergic Midbrain Neurons In Startle And Prepulse Inhibition, Erin Azzopardi, Andrea G. Louttit, Cleusa Deoliveira, Steven R, Laviolette, Susanne Schmid

Anatomy and Cell Biology Publications

One of the two major cholinergic centers of the mammalian brain is located in the midbrain, i.e., the pedunculopontine tegmentum (PPTg) and the adjacent laterodorsal tegmentum. These cholinergic neurons have been shown to be important for e.g., arousal, reward associations, and sleep. They also have been suggested to mediate sensorimotor gating, measured as prepulse inhibition of startle (PPI). PPI disruptions are a hallmark of schizophrenia and are observed in various other psychiatric disorders, where they are associated with, and often predictive of, other cognitive symptoms. PPI has been proposed to be mediated by a short midbrain circuitry including inhibitory cholinergic …

Als Yeast Models-Past Success Stories And New Opportunities, Sonja E. Di Gregorio, Martin L. Duennwald

Anatomy and Cell Biology Publications

In the past two decades, yeast models have delivered profound insights into basic mechanisms of protein misfolding and the dysfunction of key cellular pathways associated with amyotrophic lateral sclerosis (ALS). Expressing ALS-associated proteins, such as superoxide dismutase (SOD1), TAR DNA binding protein 43 (TDP-43) and Fused in sarcoma (FUS), in yeast recapitulates major hallmarks of ALS pathology, including protein aggregation, mislocalization and cellular toxicity. Results from yeast have consistently been recapitulated in other model systems and even specimens from human patients, thus providing evidence for the power and validity of ALS yeast models. Focusing on impaired ribonucleic acid (RNA) metabolism …

Everolimus In Advanced Breast Cancer: A Systematic Review And Meta-Analysis, J Raphael, C Lefebvre, A Allan, J Helou, G Boldt, T Vandenberg

Anatomy and Cell Biology Publications

No abstract provided.

Behavioral Plasticity Of Audiovisual Perception: Rapid Recalibration Of Temporal Sensitivity But Not Perceptual Binding Following Adult-Onset Hearing Loss, Ashley L. Schormans, Brian L. Allaman

Anatomy and Cell Biology Publications

The ability to accurately integrate or bind stimuli from more than one sensory modality is highly dependent on the features of the stimuli, such as their intensity and relative timing. Previous studies have demonstrated that the ability to perceptually bind stimuli is impaired in various clinical conditions such as autism, dyslexia, schizophrenia, as well as aging. However, it remains unknown if adult-onset hearing loss, separate from aging, influences audiovisual temporal acuity. In the present study, rats were trained using appetitive operant conditioning to perform an audiovisual temporal order judgment (TOJ) task or synchrony judgment (SJ) task in order to investigate …

Overall Survival (Os) Implications For Patients With Mcrpc Through Coverage And Adoption Of Nuclear Ar-V7 Testing By Healthcare Systems, J Hornberger, R P. Graf, M Hulling, G Attard, A Allan, R Dittamore, H Scher

Anatomy and Cell Biology Publications

No abstract provided.

Air Pollution: A Silent Common Killer For Stroke And Dementia, Mahmoud R. Azarpazhooh, Vladimir Hachinski

Anatomy and Cell Biology Publications

No abstract provided.

Implementing The Proclamation Of Stroke And Potentially Preventable Dementias, Vladimir Hachinski, Detlev Ganten, Daniel Lackland, Reinhold Kreutz, Konstantinos Tsioufis, Werner Hacke

Anatomy and Cell Biology Publications

Brain health plays a central role in wellbeing and in the management of chronic diseases. Stroke and dementia pose the two greatest threats to brain health, but recent developments suggest the possibility that preventing stroke may also prevent some dementias: 1. A large population study showed a 32% decrease in the incidence of stroke and a concomitant 7% reduction in the incidence of dementia; 2. Treatment of atrial fibrillation resulted not only in stroke reduction, but a 48% decrease in dementia; 3. A hypothesis free analyses has shown that the first phase of Alzheimer disease involves vascular dysregulation, opening the …

Immune Checkpoints In Cancer Treatment, Matthew A. Cherubino

Student Publications

Despite the human immune system, cancer thrives in an extremely hostile environment. Cancer is the second most common cause of death in the U.S. with about 600,000 deaths every year, and cancer is expected to surpass heart disease as the most common cause of death in the U.S. Immune checkpoint inhibitors are a novel and promising therapeutic for treating cancer in its late stages.

Altered Auditory Processing, Filtering, And Reactivity N The Cntnap2 Knock-Out Rat Model For Neurodevelopmental Disorders, Kaela E. Scott, Ashley L. Schormans, Katharine Y. Pacoli, Cleusa De Oliveria, Brian L. Allman, Susanne Schmid

Anatomy and Cell Biology Publications

Sensory processing, and auditory processing in particular, is altered in individuals with neurodevelopmental disorders such as autism spectrum disorders (ASDs). The typical maturation of the auditory system is perturbed in these individuals during early development, which may underlie altered auditory reactivity that persists in later life. Of the many genes that regulate the auditory system development, loss-of-function mutations in the CNTNAP2 gene are strongly associated with language processing deficits and ASD. Therefore, using a novel Cntnap2 knock-out rat model, we tested the impact of Cntnap2 loss on auditory processing, filtering, and reactivity throughout development and young adulthood in male and …

Examining The Tissue-Level And Gross Phenotypic Effects Of The Connexin43i130t/+ Mutation On The Developing Mouse Skull, Sommer G.E. Jarvis

Electronic Thesis and Dissertation Repository

The purpose of this study was to investigate the effects of reduced Connexin43 function on the developing skull phenotype, osteoblast and chondrocyte proliferation and differentiation, and to determine if a correlation exists between cell processes and gross morphology. Using the Cx43^I130T/+mouse model, skull shape was analyzed using geometric morphometrics and cell proliferation and differentiation were assessed using immunohistochemistry at late embryonic and early post-natal stages. The largest shape changes between Cx43^I130T/+ and wildtype mice were observed in the cranial base and facial skeleton. Changes infacial morphology correspond to reduced osteoblast differentiation. However, no changes in chondrocyte proliferation …

Comparative Proteomic Analyses Of Human Adipose Extracellular Matrices Decellularized Using Alternative Procedures, Caasy Porch-Thomas, Jie Li, Fabiana Zanata, Elizabeth C. Martin, Nicholas Pashos, Kaylynn Genemaras, Nicholas J. Poche, Nicholas P. Totaro, Melyssa R. Bratton, Dina Gaupp, Trivia Frazier, Xiying Wu, Lydia Masako Ferreira, Weidong Tian, Guangdi Wang, Bruce A. Bunnell, Lauren Flynn, Daniel Hayes, Jeffrey M. Gimble

Anatomy and Cell Biology Publications

Decellularized human adipose tissue has potential clinical utility as a processed biological scaffold for soft tissue cosmesis, grafting, and reconstruction. Adipose tissue decellularization has been accomplished using enzymatic-, detergent-, and/or solvent-based methods. To examine the hypothesis that distinct decellularization processes may yield scaffolds with differing compositions, the current study employed mass spectrometry to compare the proteomes of human adipose-derived matrices generated through three independent methods combining enzymatic-, detergent-, and/or solvent-based steps. In addition to protein content, bioscaffolds were evaluated for deoxyribose nucleic acid depletion, extracellular matrix composition, and physical structure using optical density, histochemical staining, and scanning electron microscopy. Mass …

App21 Transgenic Rats Develop Age-Dependent Cognitive Impairment And Microglia Accumulation Within White Matter Tracts, Nina Weishaupt, Qingfan Liu, Sheojung Shin, Ramandeep Singh, Yuksel Agca, Cansu Agca, Vladimir Hachinski, Shawn Narain Whitehead

Anatomy and Cell Biology Publications

Background: Most of the animal models commonly used for preclinical research into Alzheimer's disease (AD) largely fail to address the pathophysiology, including the impact of known risk factors, of the widely diagnosed sporadic form of the disease. Here, we use a transgenic rat (APP21) that does not develop AD-like pathology spontaneously with age, but does develop pathology following vascular stress. To further the potential of this novel rat model as a much-needed pre-clinical animal model of sporadic AD, we characterize APP21 transgenic rats behaviorally and histologically up to 19 months of age. Methods: The open field test was used as …

Targeting The Mitochondrial Permeability Transition Pore In Traumatic Central Nervous System Injury, Joe E. Springer, Pareshkumar Prajapati, Patrick G. Sullivan

Spinal Cord and Brain Injury Research Center Faculty Publications

The mitochondrion serves many functions in the central nervous system (CNS) and other organs beyond the well-recognized role of adenosine triphosphate (ATP) production. This includes calcium-dependent cell signaling, regulation of gene expression, synthesis and release of cytotoxic reactive oxygen species, and the release of cytochrome c and other apoptotic cell death factors. Traumatic injury to the CNS results in a rapid and, in some cases, sustained loss of mitochondrial function. One consequence of compromised mitochondrial function is induction of the mitochondrial permeability transition (mPT) state due to formation of the cyclosporine A sensitive permeability transition pore (mPTP). In this mini-review, …

Unfolded Protein Response Pathways In Skeletal Muscle Homeostasis., Kyle R. Bohnert

Electronic Theses and Dissertations

Skeletal muscle mass, contractile properties, and metabolic function are regulated through the coordinated activation of multiple intracellular signaling pathways and genetic reprogramming. The endoplasmic reticulum (ER) plays a pivotal role in protein folding and calcium homeostasis in many cell types, including skeletal muscle. Disruption of calcium levels or accumulation of misfolded proteins in the ER lumen leads to stress, which results in the activation of a signaling network called the unfolded protein response (UPR). Further, recent studies have suggested that in certain conditions, UPR pathways can be activated independent of ER stress. However, the role of ER stress and the …

Histone Deacetylase 8 Protects Human Proximal Tubular Epithelial Cells From Hypoxia-Mimetic Cobalt- And Hypoxia/Reoxygenation-Induced Mitochondrial Fission And Cytotoxicity, Soon-Duck Ha, Ori Solomon, Masoud Akbari, Alp Sener, Sung Ouk Kim

Anatomy and Cell Biology Publications

Cell death by hypoxia followed by reoxygenation (H/R) is responsible for tissue injury in multiple pathological conditions. Recent studies found that epigenetic reprogramming mediated by histone deacetylases (HDACs) is implicated in H/R-induced cell death. However, among 18 different isoforms comprising 4 classes (I-IV), the role of each HDAC in cell death is largely unknown. This study examined the role of HDAC8, which is the most distinct isoform of class I, in the hypoxia mimetic cobalt- and H/R-induced cytotoxicity of human proximal tubular HK-2 cells. Using the HDAC8-specific activator TM-2-51 (TM) and inhibitor PCI34051, we found that HDAC8 played a protective …

Extrinsic And Intrinsic Factors In Liver Development, Amrita Palaria

Doctoral Dissertations

Liver is the largest internal organ of the human body. It performs a multitude of functions. Therefore, it is provided with a huge regenerative capacity however, because of the same reason it is also prone to various diseases. Hence, it is essential to understand liver development in order to understand liver regeneration and liver diseases to provide better therapeutic targets and solutions. Liver development is orchestrated by a variety of intrinsic and extrinsic factors. The major focus of this dissertation thesis is to elucidate the role of BMP signals and YY1/VEGFA regulated signals in liver development. Liver organogenesis initiates with …

Direct Cell-To-Cell Transmission Of Respiratory Viruses: The Fast Lanes, Nicolás P. Cifuentes-Muñoz, Rebecca Ellis Dutch, Roberto Cattaneo

Molecular and Cellular Biochemistry Faculty Publications

Virus particles protect genomes from hostile environments within and outside the host, eventually delivering these genomes to target tissues to initiate infection. Complex processes requiring significant energy and time are necessary to assemble these virus particles, but only a small portion of released virus will successfully infect new target cells (Fig 1A). While the science of virology has developed based on the isolation and purification of viral particles, it is becoming increasingly clear that direct cell-to-cell transmission of viruses and/or viral components is also highly relevant [1,2].

Direct cell-to-cell spread of infections has several advantages. The first is efficiency: genomic …