Digital Commons Network^™

Paeonol Ameliorates Chronic Itch And Spinal Astrocytic Activation Via Cxcr3 In An Experimental Dry Skin Model In Mice, Wen Wang, Qiaoyun Li, Zhongqiu Zhao, Yutong Liu, Yi Wang, Hui Xiong, Zhinan Mei

Open Access Publications

Paeonol is a bioactive phenol presents mainly in

Perceptions Of Clinical Dental Students Toward Online Education During The Covid-19 Crisis: An Egyptian Multicenter Cross-Sectional Survey, Reham Hassan, Ayman R Khalifa, Tarek Elsewify, Mohamed G Hassan

Open Access Publications

No abstract provided.

Superior Verbal Memory Outcome After Stereotactic Laser Amygdalohippocampotomy, Daniel L Drane, Jon T Willie, Et Al

Open Access Publications

No abstract provided.

Care Gaps And Recommendations In Vestibular Migraine: An Expert Panel Summit, Monica P Mallampalli, Joel A Goebel, Et Al

Open Access Publications

Vestibular migraine (VM) is an increasingly recognized pathology yet remains as an underdiagnosed cause of vestibular disorders. While current diagnostic criteria are codified in the 2012 Barany Society document and included in the third edition of the international classification of headache disorders, the pathophysiology of this disorder is still elusive. The Association for Migraine Disorders hosted a multidisciplinary, international expert workshop in October 2020 and identified seven current care gaps that the scientific community needs to resolve, including a better understanding of the range of symptoms and phenotypes of VM, the lack of a diagnostic marker, a better understanding of …

Encephalitic Arboviruses Of Africa: Emergence, Clinical Presentation And Neuropathogenesis, Robyn S Klein

Open Access Publications

Many mosquito-borne viruses (arboviruses) are endemic in Africa, contributing to systemic and neurological infections in various geographical locations on the continent. While most arboviral infections do not lead to neuroinvasive diseases of the central nervous system, neurologic diseases caused by arboviruses include flaccid paralysis, meningitis, encephalitis, myelitis, encephalomyelitis, neuritis, and post-infectious autoimmune or memory disorders. Here we review endemic members of the

Hyperexcitability Of Sensory Neurons In Fragile X Mouse Model, Pan-Yue Deng, Oshri Avraham, Valeria Cavalli, Vitaly A Klyachko

Open Access Publications

Sensory hypersensitivity and somatosensory deficits represent the core symptoms of Fragile X syndrome (FXS). These alterations are believed to arise from changes in cortical sensory processing, while potential deficits in the function of peripheral sensory neurons residing in dorsal root ganglia remain unexplored. We found that peripheral sensory neurons exhibit pronounced hyperexcitability in

Rubella Virus Infected Macrophages And Neutrophils Define Patterns Of Granulomatous Inflammation In Inborn And Acquired Errors Of Immunity, Ludmila Perelygina, Amy Musiek, Et Al

Open Access Publications

Rubella virus (RuV) has recently been found in association with granulomatous inflammation of the skin and several internal organs in patients with inborn errors of immunity (IEI). The cellular tropism and molecular mechanisms of RuV persistence and pathogenesis in select immunocompromised hosts are not clear. We provide clinical, immunological, virological, and histological data on a cohort of 28 patients with a broad spectrum of IEI and RuV-associated granulomas in skin and nine extracutaneous tissues to further delineate this relationship. Combined immunodeficiency was the most frequent diagnosis (67.8%) among patients. Patients with previously undocumented conditions, i.e., humoral immunodeficiencies, a secondary immunodeficiency, …

A Real-World Observation Of Antipsychotic Effects On Brain Volumes And Intrinsic Brain Activity In Schizophrenia, Yifan Chen, Fay Y Womer, Ruiqi Feng, Xizhe Zhang, Yanbo Zhang, Jia Duan, Miao Chang, Zhiyang Yin, Xiaowei Jiang, Shengnan Wei, Yange Wei, Yanqing Tang, Fei Wang

Open Access Publications

Background: The confounding effects of antipsychotics that led to the inconsistencies of neuroimaging findings have long been the barriers to understanding the pathophysiology of schizophrenia (SZ). Although it is widely accepted that antipsychotics can alleviate psychotic symptoms during the early most acute phase, the longer-term effects of antipsychotics on the brain have been unclear. This study aims to look at the susceptibility of different imaging measures to longer-term medicated status through real-world observation.

Methods: We compared gray matter volume (GMV) with amplitude of low-frequency fluctuations (ALFFs) in 89 medicated-schizophrenia (med-SZ), 81 unmedicated-schizophrenia (unmed-SZ), and 235 healthy controls (HC), and the …

Development And Testing Of A Spray-Dried Tuberculosis Vaccine Candidate In A Mouse Model, Mellissa Gomez, Mushtaq Ahmed, Shibali Das, Leah Mellett, Rosemary Swanson, Ananya Gupta, Shabaana A Khader, Et Al

Open Access Publications

Converting a vaccine into a thermostable dry powder is advantageous as it reduces the resource burden linked with the cold chain and provides flexibility in dosage and administration through different routes. Such a dry powder presentation may be especially useful in the development of a vaccine towards the respiratory infectious disease tuberculosis (TB). This study assesses the immunogenicity and protective efficacy of spray-dried ID93+GLA-SE, a promising TB vaccine candidate, against

The T-Type Calcium Channel Isoform Ca V 3.1 Is A Target For The Hypnotic Effect Of The Anaesthetic Neurosteroid (3Β,5Β,17Β)-3-Hydroxyandrostane-17-Carbonitrile, Tamara Timic Stamenic, Simon Feseha, Francesca M Manzella, Damon Wallace, Davis Wilkey, Timothy Corrigan, Hanna Fiedler, Patricia Doerr, Kathiresan Krishnan, Yogendra H Raol, Douglas F Covey, Vesna Jevtovic-Todorovic, Slobodan M Todorovic

Open Access Publications

BACKGROUND: The mechanisms underlying the role of T-type calcium channels (T-channels) in thalamocortical excitability and oscillations in vivo during neurosteroid-induced hypnosis are largely unknown.

METHODS: We used patch-clamp electrophysiological recordings from acute brain slices ex vivo, recordings of local field potentials (LFPs) from the central medial thalamic nucleus in vivo, and wild-type (WT) and Ca

RESULTS: Patch-clamp recordings showed that 3β-OH inhibited isolated T-currents but had no effect on phasic or tonic γ-aminobutyric acid A currents. Also in acute brain slices, 3β-OH inhibited the spike firing mode more profoundly in WT than in Ca

CONCLUSIONS: The Ca

Clip And Massively Parallel Functional Analysis Of Celf6 Reveal A Role In Destabilizing Synaptic Gene Mrnas Through Interaction With 3' Utr Elements, Michael A Rieger, Dana M King, Haley Crosby, Yating Liu, Barak A Cohen, Joseph D Dougherty

Open Access Publications

CELF6 is a CELF-RNA-binding protein, and thus part of a protein family with roles in human disease; however, its mRNA targets in the brain are largely unknown. Using cross-linking immunoprecipitation and sequencing (CLIP-seq), we define its CNS targets, which are enriched for 3' UTRs in synaptic protein-coding genes. Using a massively parallel reporter assay framework, we test the consequence of CELF6 expression on target sequences, with and without mutating putative binding motifs. Where CELF6 exerts an effect on sequences, it is largely to decrease RNA abundance, which is reversed by mutating UGU-rich motifs. This is also the case for CELF3-5, …

Neutrophil Elastase Facilitates Tumor Cell Intravasation And Early Metastatic Events, Elena Deryugina, Alexia Carré, Veronica Ardi, Tomoki Muramatsu, Jonas Schmidt, Christine Pham, James P Quigley

Open Access Publications

Functional roles of neutrophil elastase (NE) have not been examined in distinct steps of the metastatic cascade. NE, delivered to primary tumors as a purified enzyme or within intact neutrophils or neutrophil granule content, enhanced human tumor cell intravasation and subsequent dissemination via NE-mediated formation of dilated intratumoral vasculature. These effects depended on picomole range of NE activity, sensitive to its natural inhibitor, α1PI. In

Neuroplastin Modulates Anti-Inflammatory Effects Of Manf, Takuya Yagi, Rie Asada, Kohsuke Kanekura, Ave Eesmaa, Maria Lindahl, Mart Saarma, Fumihiko Urano

Open Access Publications

Endoplasmic reticulum (ER) stress is known to induce pro-inflammatory response and ultimately leads to cell death. Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an ER-localized protein whose expression and secretion is induced by ER stress and a crucial survival factor. However, the underlying mechanism of how MANF exerts its cytoprotective activity remains unclear due to the lack of knowledge of its receptor. Here we show that Neuroplastin (NPTN) is such a receptor for MANF. Biochemical analysis shows the physiological interaction between MANF and NPTN on the cell surface. Binding of MANF to NPTN mitigates the inflammatory response and apoptosis via suppression …

Evaluation Of Surrogate Tests For The Presence Of Meca-Mediated Methicillin Resistance In Staphylococcus Capitis, Staphylococcus Haemolyticus, Staphylococcus Hominis, And Staphylococcus Warneri, Romney M Humphries, Paul Magnano, C A Burnham, Jennifer Dien Bard, Tanis C Dingle, Katrina Callan, Lars F Westblade

Open Access Publications

Testing of staphylococci other than

Neonatal Mouse Gut Metabolites Influence Cryptosporidium Parvum Infection In Intestinal Epithelial Cells, Kelli L Vandussen, Lisa J Funkhouser-Jones, Marianna E Akey, Deborah A Schaefer, Kevin Ackman, Michael W Riggs, Thaddeus S Stappenbeck, L David Sibley

Open Access Publications

The protozoan parasite

Yap And Taz Maintain Prox1 Expression In The Developing Lymphatic And Lymphovenous Valves In Response To Vegf-C Signaling, Boksik Cha, Yen-Chun Ho, Xin Geng, Md Riaj Mahamud, Lijuan Chen, Yeunhee Kim, Dongwon Choi, Tae Hoon Kim, Gwendalyn J Randolph, Xinwei Cao, Hong Chen, R Sathish Srinivasan

Open Access Publications

Lymphatic vasculature is an integral part of digestive, immune and circulatory systems. The homeobox transcription factor PROX1 is necessary for the development of lymphatic vessels, lymphatic valves (LVs) and lymphovenous valves (LVVs). We and others previously reported a feedback loop between PROX1 and vascular endothelial growth factor-C (VEGF-C) signaling. PROX1 promotes the expression of the VEGF-C receptor VEGFR3 in lymphatic endothelial cells (LECs). In turn, VEGF-C signaling maintains PROX1 expression in LECs. However, the mechanisms of PROX1/VEGF-C feedback loop remain poorly understood. Whether VEGF-C signaling is necessary for LV and LVV development is also unknown. Here, we report for the …

Macrophage-Derived Vascular Endothelial Growth Factor-A Is Integral To Neuromuscular Junction Reinnervation After Nerve Injury, Chuieng-Yi Lu, Katherine B. Santosa, Albina Jablonka-Shariff, Bianca Vannucci, Anja Fuchs, Isaiah Turnbull, Deng Pan, Matthew D. Wood, Alison K. Snyder-Warwick

Open Access Publications

Functional recovery in the end target muscle is a determinant of outcome after peripheral nerve injury. The neuromuscular junction (NMJ) provides the interface between nerve and muscle and includes non-myelinating terminal Schwann cells (tSCs). After nerve injury, tSCs extend cytoplasmic processes between NMJs to guide axon growth and NMJ reinnervation. The mechanisms related to NMJ reinnervation are not known. We used multiple mouse models to investigate the mechanisms of NMJ reinnervation in both sexes, specifically whether macrophage-derived vascular endothelial growth factor-A (Vegf-A) is crucial to establishing NMJ reinnervation at the end target muscle. Both macrophage number and Vegf-A expression increased …

Stem Cell And Niche Regulation In Human Short Bowel Syndrome, Vered A Gazit, Elzbieta A Swietlicki, Miranda U Liang, Adam Surti, Raechel Mcdaniel, Mackenzie Geisman, David M Alvarado, Matthew A Ciorba, Grant Bochicchio, Obeid Ilahi, John Kirby, William J Symons, Nicholas O Davidson, Marc S. Levin, Deborah C Rubin

Open Access Publications

Loss of functional small bowel surface area following surgical resection for disorders such as Crohn's disease, intestinal ischemic injury, radiation enteritis, and in children, necrotizing enterocolitis, atresia, and gastroschisis, may result in short bowel syndrome, with attendant high morbidity, mortality, and health care costs in the United States. Following resection, the remaining small bowel epithelium mounts an adaptive response, resulting in increased crypt cell proliferation, increased villus height, increased crypt depth, and enhanced nutrient and electrolyte absorption. Although these morphologic and functional changes are well described in animal models, the adaptive response in humans is less well understood. Clinically the …

Humoral Immune Responses Mediate The Development Of A Restrictive Phenotype Of Chronic Lung Allograft Dysfunction, Keizo Misumi, David S Wheeler, Yoshiro Aoki, Michael P Combs, Russell R Braeuer, Ryuji Higashikubo, Wenjun Li, Daniel Kreisel, Ragini Vittal, Jeffrey Myers, Amir Lagstein, Natalie M Walker, Carol F Farver, Vibha N Lama

Open Access Publications

Understanding the distinct pathogenic mechanisms that culminate in allograft fibrosis and chronic graft failure is key in improving outcomes after solid organ transplantation. Here, we describe an F1 → parent orthotopic lung transplant model of restrictive allograft syndrome (RAS), a particularly fulminant form of chronic lung allograft dysfunction (CLAD), and identify a requisite pathogenic role for humoral immune responses in development of RAS. B6D2F1/J (H2-b/d) donor lungs transplanted into the parent C57BL/6J (H2-b) recipients demonstrated a spectrum of histopathologic changes, ranging from lymphocytic infiltration, fibrinous exudates, and endothelialitis to peribronchial and pleuroparenchymal fibrosis, similar to those noted in the human …

The Effects Of Early-Treated Phenylketonuria On Volumetric Measures Of The Cerebellum, Kristina Aldridge, Kimberly K Cole, Amanda J Moffitt Gunn, Dawn Peck, Desirée A White, Shawn E Christ

Open Access Publications

Past murine studies of phenylketonuria (PKU) have documented significant effects on cerebellum at both the gross and cellular levels. The profile of neurocognitive and motor difficulties associated with early-treated PKU (ETPKU) is also consistent with potential cerebellar involvement. Previous neuroanatomical studies of cerebellum in patients with PKU, however, have yielded mixed results. The objective of the present study was to further examine potential differences in cerebellar morphometry between individuals with and without ETPKU. To this end, we analyzed high resolution T1-weighted MR images from a sample of 20 individuals with ETPKU and an age-matched comparison group of 20 healthy individuals …

Positive Information Facilitates Response Inhibition In Older Adults Only When Emotion Is Task-Relevant, Samantha E Williams, Eric J Lenze, Jill D Waring

Open Access Publications

Emotional information is integral to everyday life and impacts a variety of cognitive abilities including response inhibition, a critical skill for maintaining appropriate and flexible behaviour. However, reported effects of emotion on response inhibition are inconsistent in younger adults, and very limited in older adults. Effects of aging are especially relevant because emotion regulation improves with aging despite declining inhibitory control over neutral information. Across three studies, we assessed the impact of emotional facial expressions on response inhibition in younger and older adults while manipulating attention to task stimuli. Emotional faces (versus neutral faces) altered response inhibition only when task …

Prenatal Stress Exposure And Multimodal Assessment Of Amygdala-Medial Prefrontal Cortex Connectivity In Infants, Kathryn L Humphreys, M C Camacho, Marissa C Roth, Elizabeth C Estes

Open Access Publications

Stressful experiences are linked to neurodevelopment. There is growing interest in the role of stress in the connectivity between the amygdala and medial prefrontal cortex (mPFC), a circuit that subserves automatic emotion regulation. However, the specific timing and mechanisms that underlie the association between stress and amygdala-mPFC connectivity are unclear. Many factors, including variations in fetal exposure to maternal stress, appear to affect early developing brain circuitry. However, few studies have examined the associations of stress and amygdala-mPFC connectivity in early life, when the brain is most plastic and sensitive to environmental influence. In this longitudinal pilot study, we characterized …

Rev-Erbα Mediates Complement Expression And Diurnal Regulation Of Microglial Synaptic Phagocytosis, Percy Griffin, Patrick W. Sheehan, Julie M. Dimitry, Chun Guo, Michael F. Kanan, Jiyeon Lee, Jinsong Zhang, Erik S. Musiek

Open Access Publications

The circadian clock regulates various aspects of brain health including microglial and astrocyte activation. Here, we report that deletion of the master clock protein BMAL1 in mice robustly increases expression of complement genes, including

The Intriguing Interaction Of Escherichia Coli With The Host Environment And Innovative Strategies To Interfere With Colonization: A Summary Of The 2019 E. Coli And The Mucosal Immune System Meeting, Eric Cox, Meryem Aloulou, James M Fleckenstein, Christina Schäffer, Åsa Sjöling, Stephanie Schüller, Kurt Hanevik, Bert Devriendt, Weiping Zhang, Ann-Mari Svennerholm, Edward G Dudley

Open Access Publications

The third

Transcriptional Remodeling Patterns In Murine Dendritic Cells Infected With Paracoccidioides Brasiliensis: More Is Not Necessarily Better, Calliandra M De-Souza-Silva, Fabián Andrés Hurtado, Aldo Henrique Tavares, Getúlio P De Oliveira, Taina Raiol, Christiane Nishibe, Daniel Paiva Agustinho, Nalvo Franco Almeida, Maria Emília Machado Telles Walter, André Moraes Nicola, Anamélia Lorenzetti Bocca, Patrícia Albuquerque, Ildinete Silva-Pereira

Open Access Publications

Most people infected with the fungus

Structure Of The Receptor Binding Domain Of Envp(B)1, An Endogenous Retroviral Envelope Protein Expressed In Human Tissues, Kevin R Mccarthy, Joseph L Timpona, Simon Jenni, Louis-Marie Bloyet, Vesna Brusic, Welkin E Johnson, Sean P J Whelan, Lindsey R Robinson-Mccarthy

Open Access Publications

EnvP(b)1 is an endogenous retroviral envelope gene found in human and other primate genomes. We report EnvP(b)1 sequences in primate genomes consistent with an integration event between 40 and 71 million years ago. Using a highly specific polyclonal antiserum raised against the putative receptor binding domain (RBD) of human EnvP(b)1, we detected expression in human placenta, ovaries, and thymus. We found that EnvP(b)1 is proteolytically processed, and using cell-cell fusion assays in multiple primate cell lines, we demonstrated that extant EnvP(b)1 proteins from a variety of primate genomes are fusogenic. This work supports the idea that EnvP(b)1 is under purifying …

Increased Mtor Activity And Metabolic Efficiency In Mouse And Human Cells Containing The African-Centric Tumor-Predisposing P53 Variant Pro47ser, Keerthana Gnanapradeepan, Julia I-Ju Leu, Subhasree Basu, Thibaut Barnoud, Madeline Good, Joyce V. Lee, William J. Quinn, Che-Pei Kung, Rexford Ahima, Joseph A. Baur, Kathryn E. Wellen, Qin Liu, Zachary T. Schug, Donna L. George, Maureen E. Murphy

Open Access Publications

The Pro47Ser variant of p53 (S47) exists in African-descent populations and is associated with increased cancer risk in humans and mice. Due to impaired repression of the cystine importer

Kir6.1- And Sur2-Dependent Katp Over-Activity Disrupts Intestinal Motility In Murine Models Of Cantu Syndrome, Nathaniel W York, Helen Parker, Zili Xie, David Tyus, Maham A Waheed, Zihan Yan, Dorothy K Grange, Maria S Remedi, Sarah K England, Hongzhen Hu, Colin G Nichols

Open Access Publications

Cantύ Syndrome (CS), caused by gain-of-function (GOF) mutations in pore-forming (Kir6.1, KCNJ8) and accessory (SUR2, ABCC9) ATP-sensitive potassium (KATP) channel subunit genes, is frequently accompanied by gastrointestinal (GI) dysmotility, and we describe one CS patient who required an implanted intestinal irrigation system for successful stooling. We used gene-modified mice to assess the underlying KATP channel subunits in gut smooth muscle, and to model the consequences of altered KATP channels in CS gut. We show that Kir6.1/SUR2 subunits underlie smooth muscle KATP channels throughout the small intestine and colon. Knock-in mice, carrying human KCNJ8 and ABCC9 CS mutations in the endogenous …

Myh3-Associated Distal Arthrogryposis Zebrafish Model Is Normalized With Para-Aminoblebbistatin, Julia Whittle, Lilian Antunes, Mya Harris, Zachary Upshaw, Diane S Sepich, Aaron N Johnson, Mayssa Mokalled, Lilianna Solnica-Krezel, Matthew B Dobbs, Christina A Gurnett

Open Access Publications

Distal arthrogryposis (DA) is group of syndromes characterized by congenital joint contractures. Treatment development is hindered by the lack of vertebrate models. Here, we describe a zebrafish model in which a common MYH3 missense mutation (R672H) was introduced into the orthologous zebrafish gene smyhc1 (slow myosin heavy chain 1) (R673H). We simultaneously created a smyhc1 null allele (smyhc1

Hsv-1 And Zika Virus But Not Sars-Cov-2 Replicate In The Human Cornea And Are Restricted By Corneal Type Iii Interferon, Jonathan J Miner, Derek J Platt, Cyrus M Ghaznavi, Pallavi Chandra, Andrea Santeford, Amber M Menos, Zhenyu Dong, Erin R Wang, Wei Qian, Elysse S Karozichian, Jennifer A Philips, Rajendra S Apte

Open Access Publications

Here, we report our studies of immune-mediated regulation of Zika virus (ZIKV), herpes simplex virus 1 (HSV-1), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the human cornea. We find that ZIKV can be transmitted via corneal transplantation in mice. However, in human corneal explants, we report that ZIKV does not replicate efficiently and that SARS-CoV-2 does not replicate at all. Additionally, we demonstrate that type III interferon (IFN-λ) and its receptor (IFNλR1) are expressed in the corneal epithelium. Treatment of human corneal explants with IFN-λ, and treatment of mice with IFN-λ eye drops, upregulates antiviral interferon-stimulated genes. …