Life Sciences 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 …

Brca1 And Brca2 5′ Noncoding Region Variants Identified In Breast Cancer Patients Alter Promoter Activity And Protein Binding, Leslie J. Burke, Jan Sevcik, Gaetana Gambino, Emma Tudini, Eliseos J. Mucaki, Ben C. Shirley, Phillip Whiley, Michael T. Parsons, Kim De Leeneer, Sara Gutiérrez-Enríquez, Marta Santamariña, Sandrine M. Caputo, Elizabeth Santana Dos Santos, Jana Soukupova, Marketa Janatova, Petra Zemankova, Klara Lhotova, Lenka Stolarova, Mariana Borecka, Alejandro Moles-Fernández, Siranoush Manoukian, Bernardo Bonanni, Stacey L. Edwards, Marinus J. Blok, Thomas Van Overeem Hansen, Maria Rossing, Orland Diez, Ana Vega, Kathleen B.M. Claes, David E. Goldgar, Etienne Rouleau

Biochemistry Publications

© 2018 The Authors. Human Mutation published by Wiley Periodicals, Inc. The widespread use of next generation sequencing for clinical testing is detecting an escalating number of variants in noncoding regions of the genome. The clinical significance of the majority of these variants is currently unknown, which presents a significant clinical challenge. We have screened over 6,000 early-onset and/or familial breast cancer (BC) cases collected by the ENIGMA consortium for sequence variants in the 5′ noncoding regions of BC susceptibility genes BRCA1 and BRCA2, and identified 141 rare variants with global minor allele frequency < 0.01, 76 of which have not been reported previously. Bioinformatic analysis identified a set of 21 variants most likely to impact transcriptional regulation, and luciferase reporter assays detected altered promoter activity for four of these variants. Electrophoretic mobility shift assays demonstrated that three of these altered the binding of proteins to the respective BRCA1 or BRCA2 promoter regions, including NFYA binding to BRCA1:c.-287C>T and PAX5 binding to BRCA2:c.-296C …

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 …

Dissociable Effects Of Self-Reported Daily Sleep Duration On High-Level Cognitive Abilities, Conor J. Wild, Emily S. Nichols, Michael E. Battista, Bobby Stojanoski, Adrian M. Owen

BrainsCAN Publications

© 2018 Sleep Research Society. Most people will at some point experience not getting enough sleep over a period of days, weeks, or months. However, the effects of this kind of everyday sleep restriction on high-level cognitive abilities - such as the ability to store and recall information in memory, solve problems, and communicate - remain poorly understood. In a global sample of over 10000 people, we demonstrated that cognitive performance, measured using a set of 12 well-established tests, is impaired in people who reported typically sleeping less, or more, than 7-8 hours per night - which was roughly half …

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 …

Predicting Response To Platin Chemotherapy Agents With Biochemically-Inspired Machine Learning, Peter Rogan, Eliseos J. Mucaki, Dan Lizotte

Biochemistry Publications

Selection of effective genes that accurately predict chemotherapy response could improve cancer outcomes. We compare optimized gene signatures for cisplatin, carboplatin, and oxaliplatin response in the same cell lines, and respectively validate each with cancer patient data. Supervised support vector machine learning was used to derive gene sets whose expression was related to cell line GI₅₀ values by backwards feature selection with cross-validation. Specific genes and functional pathways distinguishing sensitive from resistant cell lines are identified by contrasting signatures obtained at extreme vs. median GI₅₀ thresholds. Ensembles of gene signatures at different thresholds are combined to reduce dependence …

Mechanisms Underlying Insect Freeze Tolerance., Jantina Toxopeus, Brent J Sinclair

Biology Publications

Freeze tolerance - the ability to survive internal ice formation - has evolved repeatedly in insects, facilitating survival in environments with low temperatures and/or high risk of freezing. Surviving internal ice formation poses several challenges because freezing can cause cellular dehydration and mechanical damage, and restricts the opportunity to metabolise and respond to environmental challenges. While freeze-tolerant insects accumulate many potentially protective molecules, there is no apparent 'magic bullet' - a molecule or class of molecules that appears to be necessary or sufficient to support this cold-tolerance strategy. In addition, the mechanisms underlying freeze tolerance have been minimally explored. Herein, …

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 …

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 …

Role Of Dimensionality In Predicting The Spontaneous Behavior Of The Brain Using The Classical Ising Model And The Ising Model Implemented On A Structural Connectome, Pubuditha M. Abeyasinghe, Demetrius Ribeiro De Paula, Sina Khajehabdollahi, Sree Ram Valluri, Adrian M. Owen, Andrea Soddu

BrainsCAN Publications

© Pubuditha M. Abeyasinghe et al. 2018. There is accumulating evidence that spontaneous fluctuations of the brain are sustained by a structural architecture of axonal fiber bundles. Various models have been used to investigate this structure-function relationship. In this work, we implemented the Ising model using the number of fibers between each pair of brain regions as input. The output of the Ising model simulations on a structural connectome was then compared with empirical functional connectivity data. A simpler two-dimensional classical Ising model was used as the baseline model for comparison purpose. Thermodynamic properties, such as the magnetic susceptibility and …

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 …

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 …

Immature Auditory Evoked Potentials In Children With Moderate-Severe Developmental Language Disorder., Elaine Yuen Ling Kwok, Marc F Joanisse, Lisa Archibald, Janis Oram Cardy

Health and Rehabilitation Sciences Publications

Purpose: Immature auditory processing has been proposed to underlie language impairments in children with developmental language disorder (DLD; also known as specific language impairment). Using newly available normative auditory evoked potential (AEP) waveforms, we estimated AEP maturity in individual children with DLD and explored whether this maturational index was related to their language abilities.

Method: AEPs were elicited by 225 trials of a 490-Hz pure tone. Using intraclass correlation and our previously established normative AEP waveforms of 7- to 10-year-old children with typical development, we estimated the age equivalent of the AEPs (AEP-age) from 21 children with DLD. The relation …

N-Glycosylation Regulates Pannexin 2 Localization But Is Not Required For Interacting With Pannexin 1., Rafael E Sanchez-Pupo, Danielle Johnston, Silvia Penuela

Anatomy and Cell Biology Publications

Pannexins (Panx1, 2, 3) are channel-forming glycoproteins expressed in mammalian tissues. We previously reported that N-glycosylation acts as a regulator of the localization and intermixing of Panx1 and Panx3, but its effects on Panx2 are currently unknown. Panx1 and Panx2 intermixing can regulate channel properties, and both pannexins have been implicated in neuronal cell death after ischemia. Our objectives were to validate the predicted N-glycosylation site of Panx2 and to study the effects of Panx2 glycosylation on localization and its capacity to interact with Panx1. We used site-directed mutagenesis, enzymatic de-glycosylation, cell-surface biotinylation, co-immunoprecipitation, and confocal microscopy. Our results showed …

Comparative Analysis Of Mutant Huntingtin Binding Partners In Yeast Species., Yanding Zhao, Ashley A Zurawel, Nicole P Jenkins, Martin L Duennwald, Chao Cheng, Arminja N Kettenbach, Surachai Supattapone

Anatomy and Cell Biology Publications

Huntington's disease is caused by the pathological expansion of a polyglutamine (polyQ) stretch in Huntingtin (Htt), but the molecular mechanisms by which polyQ expansion in Htt causes toxicity in selective neuronal populations remain poorly understood. Interestingly, heterologous expression of expanded polyQ Htt is toxic in Saccharomyces cerevisiae cells, but has no effect in Schizosaccharomyces pombe, a related yeast species possessing very few endogenous polyQ or Q/N-rich proteins. Here, we used a comprehensive and unbiased mass spectrometric approach to identify proteins that bind Htt in a length-dependent manner in both species. Analysis of the expanded polyQ-associated proteins reveals marked enrichment of …

Disease-Linked Connexin26 S17f Promotes Volar Skin Abnormalities And Mild Wound Healing Defects In Mice (Vol. 8, E2845, 2017), Eric R. Press, Katanya C. Alaga, Kevin Barr, Qing Shao, Felicitas Bosen, Klaus Willecke, Dale W. Laird

Anatomy and Cell Biology Publications

No abstract provided.