Cell and Developmental Biology Commons^™

Pathological Changes In Microvascular Morphology, Density, Size And Responses Following Comorbid Cerebral Injury, Zareen Amtul, Jun Yang, Ting-Yim Lee, David F. Cechetto

Anatomy and Cell Biology Publications

Aberrations in brain microcirculation and the associated increase in blood-brain-barrier (BBB) permeability in addition to neuroinflammation and A beta deposition observed in Alzheimer's disease (AD) and ischemia have gained considerable attention recently. However, the role of microvascular homeostasis as a pathogenic substrate to disturbed microperfusion as well as an overlapping etiologic mechanism between AD and ischemia has not been thoroughly explored. In this study, we employ temporal histopathology of cerebral vasculature in a rat model of beta-amyloid (A beta) toxicity and endothelin-1 induced-ischemia (ET1) to investigate the panorama of cerebral pathology and the protein expression on d1, d7, and d28 …

Pathological Changes In Microvascular Morphology, Density, Size And Responses Following Comorbid Cerebral Injury, Zareen Amtul, Jun Yang, Ting-Yim Lee, David F. Cechetto

Anatomy and Cell Biology Publications

Aberrations in brain microcirculation and the associated increase in blood-brain-barrier (BBB) permeability in addition to neuroinflammation and Aβ deposition observed in Alzheimer’s disease (AD) and ischemia have gained considerable attention recently. However, the role of microvascular homeostasis as a pathogenic substrate to disturbed microperfusion as well as an overlapping etiologic mechanism between AD and ischemia has not been thoroughly explored. In this study, we employ temporal histopathology of cerebral vasculature in a rat model of β-amyloid (Aβ) toxicity and endothelin-1 induced-ischemia (ET1) to investigate the panorama of cerebral pathology and the protein expression on d1, d7, and d28 post-injury. The …

Moderating Effect Of Cortical Thickness On Bold Signal Variability Age-Related Changes, Daiana R. Pur, Roy Eagleson, Anik De Ribaupierre, Nathalie Mella, Sandrine De Ribaupierre

Anatomy and Cell Biology Publications

The time course of neuroanatomical structural and functional measures across the lifespan is commonly reported in association with aging. Blood oxygen-level dependent signal variability, estimated using the standard deviation of the signal, or "BOLDSD", is an emerging metric of variability in neural processing, and has been shown to be positively correlated with cognitive flexibility. Generally, BOLDSD is reported to decrease with aging, and is thought to reflect age-related cognitive decline. Additionally, it is well established that normative aging is associated with structural changes in brain regions, and that these predict functional decline in various cognitive domains. Nevertheless, the interaction between …

Ablation Of Both Cx40 And Panx1 Results In Similar Cardiovascular Phenotypes Exhibited In Cx40 Knockout Mice, Nicole M. Novielli-Kuntz, Meghan L. Jelen, Kevin Barr, Leon J. Delalio, Qingping Feng, Brant E. Isakson, Robert Gros, Dale Laird

Anatomy and Cell Biology Publications

Connexins (Cxs) and pannexins (Panxs) are highly regulated large-pore channel-forming proteins that participate in cellular communication via small molecular exchange with the extracellular microenvironment, or in the case of connexins, directly between cells. Given the putative functional overlap between single membrane-spanning connexin hemichannels and Panx channels, and cardiovascular system prevalence, we generated the first Cx40(-/-)Panx1(-/-) mouse with the anticipation that this genetic modification would lead to a severe cardiovascular phenotype. Mice null for both Cx40 and Panx1 produced litter sizes and adult growth progression similar to wild-type (WT), Cx40(-/-) and Panx1(-/-) mice. Akin to Cx40(-/-) mice, Cx40(-/-) Panx1(-/-) mice exhibited …

Predicting Alzheimer’S Disease Progression Using Multi-Modal Deep Learning Approach, Garam Lee, Kwangsik Nho, Byungkon Kang, Kyung-Ah Sohn, Dokyoon Kim, Alzheimer's Disease Neuroimaging Initiative

Anatomy and Cell Biology Publications

Alzheimer’s disease (AD) is a progressive neurodegenerative condition marked by a decline in cognitive functions with no validated disease modifying treatment. It is critical for timely treatment to detect AD in its earlier stage before clinical manifestation. Mild cognitive impairment (MCI) is an intermediate stage between cognitively normal older adults and AD. To predict conversion from MCI to probable AD, we applied a deep learning approach, multimodal recurrent neural network. We developed an integrative framework that combines not only cross-sectional neuroimaging biomarkers at baseline but also longitudinal cerebrospinal fluid (CSF) and cognitive performance biomarkers obtained from the Alzheimer’s Disease Neuroimaging …

Fluctuation Of Primary Motor Cortex Excitability During Cataplexy In Narcolepsy, Bei Huang, Zhenying Qian, Zongwen Wang, Jihui Zhang, Kun Chen, Tao Xu, Jijun Wang, David F. Cechetto, Zhongxin Zhao, Huijuan Wu

Anatomy and Cell Biology Publications

Objective Cataplexy is a complicated and dynamic process in narcolepsy type 1 (NT1) patients. This study aimed to clarify the distinct stages during a cataplectic attack and identify the changes of the primary motor cortex (PMC) excitability during these stages. Methods Thirty-five patients with NT1 and 29 healthy controls were recruited to this study. Cataplectic stages were distinguished from a cataplectic attack by video-polysomnogram monitoring. Transcranial magnetic stimulation motor-evoked potential (TMS-MEP) was performed to measure the excitability of PMC during quiet wakefulness, laughter without cataplexy, and each cataplectic stage. Results Based on the video and electromyogram observations, a typical cataplectic …

Detection Of Active Caspase-3 In Mouse Models Of Stroke And Alzheimer's Disease With A Novel Dual Positron Emission Tomography/Fluorescent Tracer [68ga]Ga-Tc3-Ogdota., Valeriy G Ostapchenko, Jonatan Snir, Mojmir Suchy, Jue Fan, M.Rebecca Cobb, Blaine Chronik, Michael Kovacs, Vania F. Prado, Robert H.E. Hudson, Stephen H. Pasternak, Marco A.M. Prado, Robert Bartha

Anatomy and Cell Biology Publications

Apoptosis is a feature of stroke and Alzheimer's disease (AD), yet there is no accepted method to detect or follow apoptosis in the brain in vivo. We developed a bifunctional tracer [Ga-68]Ga-TC3-OGDOTA containing a cell-penetrating peptide separated from fluorescent Oregon Green and Ga-68-bound labels by the caspase-3 recognition peptide DEVD. We hypothesized that this design would allow [Ga-68]Ga-TC3-OGDOTA to accumulate in apoptotic cells. In vitro, Ga-TC3-OGDOTA labeled apoptotic neurons following exposure to camptothecin, oxygen-glucose deprivation, and -amyloid oligomers. In vivo, PET showed accumulation of [Ga-68]Ga-TC3-OGDOTA in the brain of mouse models of stroke or AD. Optical clearing revealed colocalization of …

Dissociable Cognitive Impairments In Two Strains Of Transgenic Alzheimer's Disease Mice Revealed By A Battery Of Object-Based Tests, Samantha D. Creighton, Ari L. Mendell, Daniel Palmer, Bettina E. Kalisch, Neil J. Maclusky, Vania F Prado, Marco A.M Prado, Boyer D. Winters

Anatomy and Cell Biology Publications

Object recognition tasks detect cognitive deficits in transgenic Alzheimer's disease (AD) mouse models. Object recognition, however, is not a unitary process, and there are many uncharacterized facets of object processing with relevance to AD. We therefore systematically evaluated object processing in 5xFAD and 3xTG AD mice to clarify the nature of object recognition-related deficits. Twelve-month-old male and female 5xFAD and 3xTG mice were assessed on tasks for object identity recognition, spatial recognition, and multisensory object perception. Memory and multisensory perceptual impairments were observed, with interesting dissociations between transgenic AD strains and sex that paralleled neuropathological changes. Overreliance on the widespread …

Effects Of Prenatal Exercise On Fetal Heart Rate, Umbilical And Uterine Blood Flow: A Systematic Review And Meta-Analysis, Rachel J. Skow, Margie H. Davenport, Michelle Mottola, Gregory A. Davies, Veronica J. Poitras, Casey E. Gray, Alejandra Jaramillo Garcia, Nick Barrowman, Victoria L. Meah, Linda G. Slater, Kristi B. Adamo, Ruben Barakat, Stephanie-May Ruchat

Anatomy and Cell Biology Publications

Objective To perform a systematic review and meta-analysis examining the influence of acute and chronic prenatal exercise on fetal heart rate (FHR) and umbilical and uterine blood flow metrics.

Design Systematic review with random-effects meta-analysis and meta-regression.

Data sources Online databases were searched up to 6 January 2017.

Study eligibility criteria Studies of all designs were included (except case studies) if published in English, Spanish or French, and contained information on the population (pregnant women without contraindication to exercise), intervention (subjective or objective measures of frequency, intensity, duration, volume or type of exercise, alone [“exercise-only”] or in combination with other …

Diffuse Intrinsic Pontine Glioma Cells Are Vulnerable To Low Intensity Electric Fields Delivered By Intratumoral Modulation Therapy, Andrew Deweyert, Erin Iredale, Hu Xu, Eugene Wong, Susanne Schmid, Matthew O. Hebb

Anatomy and Cell Biology Publications

Introduction

Diffuse intrinsic pontine glioma (DIPG) is a high fatality pediatric brain cancer without effective treatment. The field of electrotherapeutics offers new potential for other forms of glioma but the efficacy of this strategy has not been reported for DIPG. This pilot study evaluated the susceptibility of patient-derived DIPG cells to low intensity electric fields delivered using a developing technology called intratumoral modulation therapy (IMT).

Methods

DIPG cells from autopsy specimens were treated with a custom-designed, in vitro IMT system. Computer-generated electric field simulation was performed to quantify IMT amplitude and distribution using continuous, low intensity, intermediate frequency stimulation parameters. …

Double Deletion Of Panx1 And Panx3 Affects Skin And Bone But Not Hearing, J M. Abitbol, B L. O'Donnell, C B. Wakefield, E Jewlal, J J. Kelly, K Barr, K E. Willmore, B. L. Allman, S Penuela

Anatomy and Cell Biology Publications

Pannexins (Panxs), large-pore channel forming glycoproteins, are expressed in a wide variety of tissues including the skin, bone, and cochlea. To date, the use of single knock-out mouse models of both Panx1 and Panx3 have demonstrated their roles in skin development, bone formation, and auditory phenotypes. Due to sequence homology between Panx1 and Panx3, when one Panx is ablated from germline, the other may be upregulated in a compensatory mechanism to maintain tissue homeostasis and function. To evaluate the roles of Panx1 and Panx3 in the skin, bone, and cochlea, we created the first Panx1/Panx3 double knock-out mouse model (dKO). …

First M87 Event Horizon Telescope Results. I. The Shadow Of The Supermassive Black Hole, Aaron Faber, Kazunori Akiyama, Antxon Alberdi, Walter Alef, Keiichi Asada, Rebecca Azulay, Anne-Kathrin Baczko, David Ball, Mislav Baloković, John Barrett, Dan Bintley

Anatomy and Cell Biology Publications

When surrounded by a transparent emission region, black holes are expected to reveal a dark shadow caused by gravitational light bending and photon capture at the event horizon. To image and study this phenomenon, we have assembled the Event Horizon Telescope, a global very long baseline interferometry array observing at a wavelength of 1.3 mm. This allows us to reconstruct event-horizon-scale images of the supermassive black hole candidate in the center of the giant elliptical galaxy M87. We have resolved the central compact radio source as an asymmetric bright emission ring with a diameter of 42 +/- 3 mu as, …

Forebrain Cholinergic Signaling Regulates Innate Immune Responses And Inflammation, Ashbeel Roy, Vania F. Prado, Marco A.M Prado, Robert Gros, Kurt R. Lehner, Harold A. Silvernman, Meghan E. Addorissio, Mohammed A. Al-Onaizi, Yaakov Levine, Peder S. Olofsson, Sangeeta S. Chavan, Neil M. Nathanson, Yousef Al-Abed, Christine N. Metz, Kevin J. Tracey, Valentin A. Pavlov

Anatomy and Cell Biology Publications

The brain regulates physiological functions integral to survival. However, the insight into brain neuronal regulation of peripheral immune function and the neuromediator systems and pathways involved remains limited. Here, utilizing selective genetic and pharmacological approaches, we studied the role of forebrain cholinergic signaling in the regulation of peripheral immune function and inflammation. Forebrain-selective genetic ablation of acetylcholine release and vagotomy abolished the suppression of serum TNF by the centrally-acting cholinergic drug galantamine in murine endotoxemia. Selective stimulation of acetylcholine action on the M1 muscarinic acetylcholine receptor (M1 mAChR) by central administration of the positive allosteric modulator benzyl quinolone carboxylic acid …

Linked Mri Signatures Of The Brain's Acute And Persistent Response To Concussion In Female Varsity Rugby Players, Kathryn Y. Manning, Alberto Llera, Gregory A Dekaban, Robert Bartha, Christy Barreira, Arthur Brown, Lisa Fischer, Tatiana Jevremovic, Kevin A. Blackney, Tim Doherty, Douglas D. Fraser, Jeff Holmes, Christian F. Beckmann, Ravi S. Menon

Anatomy and Cell Biology Publications

Acute brain changes are expected after concussion, yet there is growing evidence of persistent abnormalities well beyond clinical recovery and clearance to return to play. Multiparametric MRI is a powerful approach to non-invasively study structure-function relationships in the brain, however it remains challenging to interpret the complex and heterogeneous cascade of brain changes that manifest after concussion. Emerging conjunctive, data-driven analysis approaches like linked independent component analysis can integrate structural and functional imaging data to produce linked components that describe the shared inter-subject variance across images. These linked components not only offer the potential of a more comprehensive understanding of …

Inhibition Of Pannexin 1 Reduces The Tumorigenic Properties Of Human Melanoma Cells, Taylor J. Freeman, Samar Sayedyahossein, Rafael E. Sanchez-Pupo, Brooke O'Donnell, Kenneth Huang, Zameena Lakhani, Daniel Nouri-Nejad, Kevin J. Barr, Luke Harland, Steven Latosinsky, Aaron Grant, Lina Dagnino, Silvia Penuela

Anatomy and Cell Biology Publications

Pannexin 1 (PANX1) is a channel-forming glycoprotein expressed in many tissues including the skin. PANX1 channels allow the passage of ions and molecules up to 1 kDa, including ATP and other metabolites. In this study, we show that PANX1 is highly expressed in human melanoma tumors at all stages of disease progression, as well as in patient-derived cells and established melanoma cell lines. Reducing PANX1 protein levels using shRNA or inhibiting channel function with the channel blockers, carbenoxolone (CBX) and probenecid (PBN), significantly decreased cell growth and migration, and increased melanin production in A375-P and A375-MA2 cell lines. Further, treatment …

The Connexin 30 A88v Mutant Reduces Cochlear Gap Junction Expression And Confers Long-Term Protection Against Hearing Loss, John J. Kelly, Julia Abitbol, Stephanie Hulme, Eric R. Press, Dale Laird, Brian L. Allman

Anatomy and Cell Biology Publications

Mutations in the genes that encode the gap junction proteins connexin 26 (Cx26, encoded by GJB2) and Cx30 (GJB6) are the leading cause of hereditary hearing loss. That said, the Cx30 p.Ala88Val (A88V) mutant causes Clouston syndrome, but not hearing loss. Here, we report that the Cx30-A88V mutant, despite being toxic to inner ear-derived HEI-OC1 cells, conferred remarkable long-term protection against age-related high frequency hearing loss in Cx30(A88V/A88V) mice. During early development, there were no overt structural differences in the cochlea between genotypes, including a normal complement of hair cells; however, the supporting cell Cx30 gap junction plaques in mutant …

The Loss Of Atrx Increases Susceptibility To Pancreatic Injury And Oncogenic Kras In Female But Not Male Mice, Claire C. Young, Ryan M. Baker, Christopher J. Howlett, Todd Hryciw, Joshua E. Herman, Douglas Higgs, Richard Gibbons, Howard Crawford, Arthur Brown, Christopher L. Pin

Anatomy and Cell Biology Publications

Female mice lacking ATRX in the pancreas have increased sensitivity to pancreatic cancer, whereas male mice without ATRX are protected. This study identifies such susceptibility in pancreatic cancer and highlights the need for sex-specific approaches in cancer treatment. BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer death in North America, accounting for >30,000 deaths annually. Although somatic activating mutations in KRAS appear in 97% of PDAC patients, additional factors are required to initiate PDAC. Because mutations in genes encoding chromatin remodelling proteins have been implicated in KRAS-mediated PDAC, we investigated whether loss of chromatin remodeler.-thalassemia, mental-retardation, …

Insulin-Like Growth Factor Binding Protein-6 Promotes The Differentiation Of Placental Mesenchymal Stem Cells Into Skeletal Muscle Independent Of Insulin-Like Growth Factor Receptor-1 And Insulin Receptor., Doaa Aboalola, Victor K M Han

Anatomy and Cell Biology Publications

As mesenchymal stem cells (MSCs) are being investigated for regenerative therapies to be used in the clinic, delineating the roles of the IGF system in MSC growth and differentiation,