Digital Commons Network^™

The Extensive And Functionally Uncharacterized Mitochondrial Phosphoproteome, Natalie M. Niemi, David J. Pagliarini

Open Access Publications

No abstract provided.

Oasis/Creb3l1 Is A Factor That Responds To Nuclear Envelope Stress, Yasunao Kamikawa, Atsushi Saito, Koji Matsuhisa, Masayuki Kaneko, Rie Asada, Yasunori Horikoshi, Satoshi Tashiro, Kazunori Imaizumi

Open Access Publications

No abstract provided.

Report From The 6th International Meeting On Bone Marrow Adiposity (Bma2020), Erica L Scheller, Meghan E Mcgee-Lawrence, Beata Lecka-Czernik

Open Access Publications

The 6

Strategies And Tools For Studying Microglial-Mediated Synapse Elimination And Refinement, Raffaella Morini, Matteo Bizzotto, Fabio Perrucci, Fabia Filipello, Michela Matteoli

Open Access Publications

The role of microglia in controlling synapse homeostasis is becoming increasingly recognized by the scientific community. In particular, the microglia-mediated elimination of supernumerary synapses during development lays the basis for the correct formation of neuronal circuits in adulthood, while the possible reactivation of this process in pathological conditions, such as schizophrenia or Alzheimer's Disease, provides a promising target for future therapeutic strategies. The methodological approaches to investigate microglial synaptic engulfment include different

Whole-Exome Sequencing And Hipsc Cardiomyocyte Models Identify Myrip, Trappc11, And Slc27a6 Of Potential Importance To Left Ventricular Hypertrophy In An African Ancestry Population, Marguerite R Irvin, Lisa De Las Fuentes, C Charles Gu, Karen Schwander, Dabeeru C Rao, Et Al

Open Access Publications

No abstract provided.

Sleep-Disordered Breathing In Pregnancy: A Developmental Origin Of Offspring Obesity?, Sarah S Farabi, Linda A Barbour, Teri L Hernandez

Open Access Publications

Sleep-disordered breathing (SDB) worsens over pregnancy, and obstructive sleep apnea is associated with serious maternal complications. Intrauterine exposures that provoke insulin resistance (IR), inflammation, or oxidative stress may have long-term offspring health consequences. In obesity, worsening maternal SDB appears to be an exposure that increases the risk for both small- or large-for-gestational-age (SGA, LGA, respectively), suggesting distinct outcomes linked to a common maternal phenotype. The aim of this paper is to systematically review and link data from both mechanistic rodent models and descriptive human studies to characterize the impact of maternal SDB on fetal development. A systematic review of the …

An Open Label, Block Randomized, Community Study Of The Safety And Efficacy Of Co-Administered Ivermectin, Diethylcarbamazine Plus Albendazole Vs. Diethylcarbamazine Plus Albendazole For Lymphatic Filariasis In India, Purushothaman Jambulingam, Vijesh Sreedhar Kuttiatt, Kaliannagounder Krishnamoorthy, Swaminathan Subramanian, Adinarayanan Srividya, Hari Kishan K. Raju, Manju Rahi, Roopali K. Somani, Mallanna K. Suryaprakash, Gangeshwar P. Dwivedi, Gary J Weil

Open Access Publications

No abstract provided.

Peripheral Sensory Stimulation Elicits Global Slow Waves By Recruiting Somatosensory Cortex Bilaterally, Zachary P. Rosenthal, Ryan V. Raut, Ryan M. Bowen, Abraham Z. Snyder, Joseph P. Culver, Marcus E. Raichle, Jin-Moo Lee

Open Access Publications

No abstract provided.

A Two-Hit Model Of Alcoholic Liver Disease That Exhibits Rapid, Severe Fibrosis, Monideepa Sengupta, Suomia Abuirqeba, Amina Kameric, Aurore Cecile-Valfort, Arindam Chatterjee, Kristine Griffett, Thomas P. Burris, Colin A. Flaveny

Open Access Publications

Alcoholic liver disease (ALD) is responsible for an average of 50.4% and 44.2%of liver disease deaths among males and females respectively. Driven by alcohol misuse, ALD is often reversible by cessation of consumption. However, abstinence programs can have limited success at curtailing abuse, and the loss of life. ALD, therefore, remains a significant clinical challenge. There is a need for effective treatments that prevent or reverse alcohol-induced liver damage to complement or supplant behavioral interventions. Metabolic syndrome, which is disproportionally prevalent in ALD patients, accelerates the progression of ALD and increases liver disease mortality. Current rodent models of ALD unfortunately …

Noise Exposure Potentiates Exocytosis From Cochlear Inner Hair Cells, Luis E Boero, Shelby Payne, Maria Eugenia Gómez-Casati, Mark A Rutherford, Juan D Goutman

Open Access Publications

Noise-induced hearing loss has gained relevance as one of the most common forms of hearing impairment. The anatomical correlates of hearing loss, principally cell damage and/or death, are relatively well-understood histologically. However, much less is known about the physiological aspects of damaged, surviving cells. Here we addressed the functional consequences of noise exposure on the capacity of inner hair cells (IHCs) to release synaptic vesicles at synapses with spiral ganglion neurons (SGNs). Mice of either sex at postnatal day (P) 15-16 were exposed to 1-12 kHz noise at 120 dB sound pressure level (SPL), for 1 h. Exocytosis was measured …

Fast Inactivation Of Nav Current In Rat Adrenal Chromaffin Cells Involves Two Independent Inactivation Pathways, Pedro L. Martinez-Espinosa, Alan Neely, Jiuping Ding, Christopher J. Lingle

Open Access Publications

Voltage-dependent sodium (Nav) current in adrenal chromaffin cells (CCs) is rapidly inactivating and tetrodotoxin (TTX)-sensitive. The fractional availability of CC Nav current has been implicated in regulation of action potential (AP) frequency and the occurrence of slow-wave burst firing. Here, through recordings of Nav current in rat CCs, primarily in adrenal medullary slices, we describe unique inactivation properties of CC Nav inactivation that help define AP firing rates in CCs. The key feature of CC Nav current is that recovery from inactivation, even following brief (5 ms) inactivation steps, exhibits two exponential components of similar amplitude. Various paired pulse protocols …

Dengue And The Lectin Pathway Of The Complement System, Romchat Kraivong, Nuntaya Punyadee, M Kathryn Liszewski, John P Atkinson, Panisadee Avirutnan

Open Access Publications

Dengue is a mosquito-borne viral disease causing significant health and economic burdens globally. The dengue virus (DENV) comprises four serotypes (DENV1-4). Usually, the primary infection is asymptomatic or causes mild dengue fever (DF), while secondary infections with a different serotype increase the risk of severe dengue disease (dengue hemorrhagic fever, DHF). Complement system activation induces inflammation and tissue injury, contributing to disease pathogenesis. However, in asymptomatic or primary infections, protective immunity largely results from the complement system's lectin pathway (LP), which is activated through foreign glycan recognition. Differences in N-glycans displayed on the DENV envelope membrane influence the lectin pattern …

Activated Microglia Mitigate Aβ-Associated Tau Seeding And Spreading, Maud Gratuze, Yun Chen, Samira Parhizkar, Nimansha Jain, Michael R. Strickland, Javier Remolina Serrano, Marco Colonna, Jason D. Ulrich, David M. Holtzman

Open Access Publications

In Alzheimer's disease (AD) models, AD risk variants in the microglial-expressed TREM2 gene decrease Aβ plaque-associated microgliosis and increase neuritic dystrophy as well as plaque-associated seeding and spreading of tau aggregates. Whether this Aβ-enhanced tau seeding/spreading is due to loss of microglial function or a toxic gain of function in TREM2-deficient microglia is unclear. Depletion of microglia in mice with established brain amyloid has no effect on amyloid but results in less spine and neuronal loss. Microglial repopulation in aged mice improved cognitive and neuronal deficits. In the context of AD pathology, we asked whether microglial removal and repopulation decreased …

Il-7 Immunotherapy In A Nonimmunocompromised Patient With Intractable Fungal Wound Sepsis, Isaiah R. Turnbull, Monty B. Mazer, Mark H. Hoofnagle, John P. Kirby, Jennifer M. Leonard, Carlos Mejia-Chew, Andrej Spec, Jane Blood, Sydney M. Miles, Eric M. Ransom, Robert F. Potter, Joseph P. Gaut, Kenneth E. Remy, Richard S. Hotchkiss

Open Access Publications

A nonimmunocompromised patient developed life-threatening soft tissue infection with

Programmed Cell Death Recruits Macrophages Into The Developing Mouse Cochlea, Vikrant Borse, Tejbeer Kaur, Ashley Hinton, Kevin Ohlemiller, Mark E Warchol

Open Access Publications

Programmed cell death (PCD) plays a critical role in the development and maturation of the cochlea. Significant remodeling occurs among cells of the greater epithelial ridge (GER) of Kölliker's organ, leading to tissue regression and formation of the inner sulcus. In mice, this event normally occurs between postnatal days 5-15 (P5-15) and is regulated by thyroid hormone (T3). During this developmental time period, the cochlea also contains a large population of macrophages. Macrophages are frequently involved in the phagocytic clearance of dead cells, both during development and after injury, but the role of macrophages in the developing cochlea is unknown. …

Follow The Metaplasia: Characteristics And Oncogenic Implications Of Metaplasia's Pattern Of Spread Throughout The Stomach, José B Sáenz

Open Access Publications

The human stomach functions as both a digestive and innate immune organ. Its main product, acid, rapidly breaks down ingested products and equally serves as a highly effective microbial filter. The gastric epithelium has evolved mechanisms to appropriately handle the myriad of injurious substances, both exogenous and endogenous, to maintain the epithelial barrier and restore homeostasis. The most significant chronic insult that the stomach must face is

Type Iii Interferons: Emerging Roles In Autoimmunity, Sindhu Manivasagam, Robyn S Klein

Open Access Publications

Type III interferons (IFNs) or the lambda IFNs (IFNLs or IFN-λs) are antimicrobial cytokines that play key roles in immune host defense at endothelial and epithelial barriers. IFNLs signal

Defining Surgical Terminology And Risk For Brain Computer Interface Technologies, Eric C Leuthardt, Daniel W Moran, Tim R Mullen

Open Access Publications

With the emergence of numerous brain computer interfaces (BCI), their form factors, and clinical applications the terminology to describe their clinical deployment and the associated risk has been vague. The terms "minimally invasive" or "non-invasive" have been commonly used, but the risk can vary widely based on the form factor and anatomic location. Thus, taken together, there needs to be a terminology that best accommodates the surgical footprint of a BCI and their attendant risks. This work presents a semantic framework that describes the BCI from a procedural standpoint and its attendant clinical risk profile. We propose extending the common …

The Role Of B Cells In Primary Progressive Multiple Sclerosis, Jameson P Holloman, Robert C Axtell, Nancy L Monson, Gregory F Wu

Open Access Publications

The success of ocrelizumab in reducing confirmed disability accumulation in primary progressive multiple sclerosis (PPMS) via CD20-targeted depletion implicates B cells as causal agents in the pathogenesis of PPMS. This review explores the possible mechanisms by which B cells contribute to disease progression in PPMS, specifically exploring cytokine production, antigen presentation, and antibody synthesis. B cells may contribute to disease progression in PPMS through cytokine production, specifically GM-CSF and IL-6, which can drive naïve T-cell differentiation into pro-inflammatory Th1/Th17 cells. B cell production of the cytokine LT-α may induce follicular dendritic cell production of CXCL13 and lead indirectly to T …

Cd11c+ Cd88+ Cd317+ Myeloid Cells Are Critical Mediators Of Persistent Cns Autoimmunity, Navid Manouchehri, Rehana Z. Hussain, Petra D. Cravens, Ekaterina Esaulova, Maxim N. Artyomov, Brian T. Edelson, Gregory F. Wu, Anne H. Cross, Richard Doelger, Nicolas Loof, Todd N. Eagar, Thomas G. Forsthuber, Laurent Calvier, Joachim Herz, Olaf Stüve

Open Access Publications

No abstract provided.

Monitoring The Variation In The Gut Microbiota Of Captive Woolly Monkeys Related To Changes In Diet During A Reintroduction Process, Camilo Quiroga-González, Luis Alberto Chica Cardenas, Mónica Ramírez, Alejandro Reyes, Camila González, Pablo R. Stevenson

Open Access Publications

No abstract provided.

Variables Associated With Intravenous Rehydration And Hospitalization In Children With Acute Gastroenteritis: A Secondary Analysis Of 2 Randomized Clinical Trials, Naveen Poonai, Philip Tarr, Et Al

Open Access Publications

Importance: Despite guidelines endorsing oral rehydration therapy, intravenous fluids are commonly administered to children with acute gastroenteritis in high-income countries.

Objective: To identify factors associated with intravenous fluid administration and hospitalization in children with acute gastroenteritis.

Design, Setting, and Participants: This study is a planned secondary analysis of the Pediatric Emergency Research Canada (PERC) and Pediatric Emergency Care Applied Research Network (PECARN) probiotic trials. Participants include children aged 3 to 48 months with 3 or more watery stools in 24 hours between November 5, 2013, and April 7, 2017, for the PERC study and July 8, 2014, and June 23, …

Lysis Of Arterial Thrombi By Perfusion Of N,N'-Diacetyl-L-Cystine (Dinac), Dongjune Kim, Susan M. Shea, David N. Ku

Open Access Publications

The search persists for a safe and effective agent to lyse arterial thrombi in the event of acute heart attacks or strokes due to thrombotic occlusion. The culpable thrombi are composed either primarily of platelets and von Willebrand Factor (VWF), or polymerized fibrin, depending on the mechanism of formation. Current thrombolytics were designed to target red fibrin-rich clots, but may be not be efficacious on white VWF-platelet-rich arterial thrombi. We have developed an in vitro system to study the efficacy of known and proposed thrombolytic agents on white clots formed from whole blood in a stenosis with arterial conditions. The …

Cannabis-Induced Hypodopaminergic Anhedonia And Cognitive Decline In Humans: Embracing Putative Induction Of Dopamine Homeostasis, Kenneth Blum, Jag Khalsa, Jean Lud Cadet, David Baron, Abdalla Bowirrat, Brent Boyett, Lisa Lott, Raymond Brewer, Marjorie Gondré-Lewis, Gregory Bunt, Shan Kazmi, Mark S Gold

Open Access Publications

Over years, the regular use of cannabis has substantially increased among young adults, as indicated by the rise in cannabis use disorder (CUD), with an estimated prevalence of 8. 3% in the United States. Research shows that exposure to cannabis is associated with hypodopaminergic anhedonia (depression), cognitive decline, poor memory, inattention, impaired learning performance, reduced dopamine brain response-associated emotionality, and increased addiction severity in young adults. The addiction medicine community is increasing concern because of the high content of delta-9-tetrahydrocannabinol (THC) currently found in oral and vaping cannabis products, the cognitive effects of cannabis may become more pronounced in young …

Thermoneutrality Alters Gastrointestinal Antigen Passage Patterning And Predisposes To Oral Antigen Sensitization In Mice, Taeko K Noah, Jee-Boong Lee, Christopher A Brown, Amnah Yamani, Sunil Tomar, Varsha Ganesan, Rodney D Newberry, Gary B Huffnagle, Senad Divanovic, Simon P Hogan

Open Access Publications

Food allergy is an emerging epidemic, and the underlying mechanisms are not well defined partly due to the lack of robust adjuvant free experimental models of dietary antigen sensitization. As housing mice at thermoneutrality (Tn) - the temperature of metabolic homeostasis (26-30°C) - has been shown to improve modeling various human diseases involved in inflammation, we tested the impact of Tn housing on an experimental model of food sensitization. Here we demonstrate that WT BALB/c mice housed under standard temperature (18-20°C, Ts) conditions translocated the luminal antigens in the small intestine (SI) across the epithelium

The Dystonia Coalition: A Multicenter Network For Clinical And Translational Studies, Gamze Kilic-Berkmen, Laura J Wright, Joel S Perlmutter, Cynthia Comella, Mark Hallett, Jan Teller, Sarah Pirio Richardson, David A Peterson, Carlos Cruchaga, Codrin Lungu, H A Jinnah

Open Access Publications

Dystonia is a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal postures, repetitive movements, or both. Research in dystonia has been challenged by several factors. First, dystonia is uncommon. Dystonia is not a single disorder but a family of heterogenous disorders with varied clinical manifestations and different causes. The different subtypes may be seen by providers in different clinical specialties including neurology, ophthalmology, otolaryngology, and others. These issues have made it difficult for any single center to recruit large numbers of subjects with specific types of dystonia for research studies in a timely manner. The Dystonia Coalition …

Myosin V Regulates Spatial Localization Of Different Forms Of Neurotransmitter Release In Central Synapses, Dario Maschi, Michael W Gramlich, Vitaly A Klyachko

Open Access Publications

Synaptic active zone (AZ) contains multiple specialized release sites for vesicle fusion. The utilization of release sites is regulated to determine spatiotemporal organization of the two main forms of synchronous release, uni-vesicular (UVR) and multi-vesicular (MVR). We previously found that the vesicle-associated molecular motor myosin V regulates temporal utilization of release sites by controlling vesicle anchoring at release sites in an activity-dependent manner. Here we show that acute inhibition of myosin V shifts preferential location of vesicle docking away from AZ center toward periphery, and results in a corresponding spatial shift in utilization of release sites during UVR. Similarly, inhibition …

Neuroskeletal Effects Of Chronic Bioelectric Nerve Stimulation In Health And Diabetes, Alec T Beeve, Ivana Shen, Xiao Zhang, Kristann Magee, Ying Yan, Matthew R Macewan, Erica L Scheller

Open Access Publications

Background/Aims: Bioelectric nerve stimulation (eStim) is an emerging clinical paradigm that can promote nerve regeneration after trauma, including within the context of diabetes. However, its ability to prevent the onset of diabetic peripheral neuropathy (DPN) has not yet been evaluated. Beyond the nerve itself, DPN has emerged as a potential contributor to sarcopenia and bone disease; thus, we hypothesized that eStim could serve as a strategy to simultaneously promote neural and musculoskeletal health in diabetes.

Methods: To address this question, an eStim paradigm pre-optimized to promote nerve regeneration was applied to the sciatic nerve, which directly innervates the tibia and …

Comprehensive Mirnome-Wide Profiling In A Neuronal Cell Model Of Synucleinopathy Implies Involvement Of Cell Cycle Genes, Elisabeth Findeiss, Sigrid C Schwarz, Valentin Evsyukov, Thomas W Rösler, Matthias Höllerhage, Tasnim Chakroun, Niko-Petteri Nykänen, Yimin Shen, Wolfgang Wurst, Michael Kohl, Jörg Tost, Günter U Höglinger

Open Access Publications

Growing evidence suggests that epigenetic mechanisms like microRNA-mediated transcriptional regulation contribute to the pathogenesis of parkinsonism. In order to study the influence of microRNAs (miRNAs), we analyzed the miRNome 2 days prior to major cell death in α-synuclein-overexpressing Lund human mesencephalic neurons, a well-established cell model of Parkinson's disease (PD), by next-generation sequencing. The expression levels of 23 miRNAs were significantly altered in α-synuclein-overexpressing cells, 11 were down- and 12 upregulated (

Whipworm-Associated Intestinal Microbiome Members Consistent Across Both Human And Mouse Hosts, Bruce A Rosa, Caroline Snowden, John Martin, Kerstin Fischer, Jonah Kupritz, Ethiopia Beshah, Taniawati Supali, Lincoln Gankpala, Peter U Fischer, Joseph F Urban, Makedonka Mitreva

Open Access Publications

The human whipworm