Digital Commons Network^™

Cgas-Sting Activation Contributes To Podocyte Injury In Diabetic Kidney Disease, Nan Zang, Chen Cui, Xinghong Guo, Jia Song, Huiqing Hu, Mengmeng Yang, Mingyue Xu, Lingshu Wang, Xinguo Hou, Qin He, Zheng Sun, Chuan Wang, Li Chen

Faculty, Staff and Students Publications

Diabetic kidney disease (DKD) is the leading cause of end-stage renal diseases. DKD does not have efficacious treatment. The cGAS-STING pathway is activated in podocytes at the early stage of kidney dysfunction, which is associated with the activation of STING downstream effectors TBK1 and NF-κB but not IRF3. Lipotoxicity induces mitochondrial damage and mtDNA leakage to the cytosol through Bcl-2 associated X protein (BAX) in podocytes. BAX-mediated mtDNA cytosolic leakage can activate the cGAS-STING pathway in the absence of lipotoxicity and is sufficient to cause podocyte injury. Depletion of cytosolic mtDNA, genetic STING knockdown, or pharmacological inhibition of STING or …

Whole Genome Sequencing Of Moraxella Bovis Strains From North America Reveals Two Genotypes With Different Genetic Determinants, Emily L. Wynn, Matthew M. Hille, John Dustin Loy, Gennie Schuller, Kristen L. Kuhn, Aaron M. Dickey, James L. Bono, Michael L. Clawson

School of Veterinary and Biomedical Sciences: Faculty Publications

Background: Moraxella bovis and Moraxella bovoculi both associate with infectious bovine keratoconjunctivitis (IBK), an economically significant and painful ocular disease that affects cattle worldwide. There are two genotypes of M. bovoculi (genotypes 1 and 2) that differ in their gene content and potential virulence factors, although neither have been experimentally shown to cause IBK. M. bovis is a causative IBK agent, however, not all strains carry a complete assortment of known virulence factors. The goals of this study were to determine the population structure and depth of M. bovis genomic diversity, and to compare core and accessory genes and …

Genetic Inhibition Of Nuclear Factor Of Activated T-Cell C2 Prevents Atrial Fibrillation In Crem Transgenic Mice, Li Ni, Satadru K Lahiri, Jiali Nie, Xiaolu Pan, Issam Abu-Taha, Julia O Reynolds, Hannah M Campbell, Haihao Wang, Markus Kamler, Wilhelm Schmitz, Frank Ulrich Müller, Na Li, Xiang Wei, Dao Wen Wang, Dobromir Dobrev, Xander H T Wehrens

Faculty, Staff and Students Publications

AIMS: Abnormal intracellular calcium (Ca2+) handling contributes to the progressive nature of atrial fibrillation (AF), the most common sustained cardiac arrhythmia. Evidence in mouse models suggests that activation of the nuclear factor of activated T-cell (NFAT) signalling pathway contributes to atrial remodelling. Our aim was to determine the role of NFATc2 in AF in humans and mouse models.

METHODS AND RESULTS: Expression levels of NFATc1-c4 isoforms were assessed by quantitative reverse transcription-polymerase chain reaction in right atrial appendages from patients with chronic AF (cAF). NFATc1 and NFATc2 mRNA levels were elevated in cAF patients compared with those in normal sinus …

Control Of Ribosomal Rna Synthesis By Hematopoietic Transcription Factors, Charles Antony, Subin S George, Justin Blum, Patrick Somers, Chelsea L Thorsheim, Dexter J Wu-Corts, Yuxi Ai, Long Gao, Kaosheng Lv, Michel G Tremblay, Tom Moss, Kai Tan, Jeremy E Wilusz, Austen R D Ganley, Maxim Pimkin, Vikram R Paralkar

Faculty, Staff and Students Publications

Ribosomal RNAs (rRNAs) are the most abundant cellular RNAs, and their synthesis from rDNA repeats by RNA polymerase I accounts for the bulk of all transcription. Despite substantial variation in rRNA transcription rates across cell types, little is known about cell-type-specific factors that bind rDNA and regulate rRNA transcription to meet tissue-specific needs. Using hematopoiesis as a model system, we mapped about 2,200 ChIP-seq datasets for 250 transcription factors (TFs) and chromatin proteins to human and mouse rDNA and identified robust binding of multiple TF families to canonical TF motifs on rDNA. Using a 47S-FISH-Flow assay developed for nascent rRNA …

Motoneuron Excitability Dysfunction In Als: Pseudo-Mystery Or Authentic Conundrum?, Sherif M. Elbasiouny

Neuroscience, Cell Biology & Physiology Faculty Publications

In amyotrophic lateral sclerosis (ALS), abnormalities in motoneuronal excitability are seen in early pathogenesis and throughout disease progression. Fully understanding motoneuron excitability dysfunction may lead to more effective treatments. Yet decades of research have not produced consensus on the nature, role or underlying mechanisms of motoneuron excitability dysfunction in ALS. For example, contrary to Ca excitotoxicity theory, predictions of motoneuronal hyper-excitability, normal and hypo-excitability have also been seen at various disease stages and in multiple ALS lines. Accordingly, motoneuron excitability dysfunction in ALS is a disputed topic in the field. Specifically, the form (hyper, hypo or unchanged) and what role …

Therapeutic Efficacy Of The Humanized Jaa-F11 Anti-Thomsen-Friedenreich Antibody Constructs H2al2a And H3l3 In Human Breast And Lung Cancer Xenograft Models, Diala Ghazal, Fatma Zalzala, John C Fisk, Swetha Tati, Loukia G Karacosta, Susan Morey, James R Olson, Sally Quataert, Grace K Dy, Kate Rittenhouse-Olson

Faculty, Staff and Student Publications

The Thomsen-Friedenreich antigen (TF-Ag-α) is found on ~85% of human carcinomas but is cryptic on normal tissue. The humanized highly specific hJAA-F11-H2aL2a and -H3L3 antibodies target TF-Ag-α without binding to TF-Ag-beta (found on surface glycolipids of some normal cells). The relative affinity of H3L3 is 17 times that of H2aL2a, which would seem to favor superior efficacy, however, increased affinity can result in less tumor penetration. To assess the potential therapeutic efficacy of these antibodies, four human cancer- mouse xenograft models were treated with H2aL2a and H3L3. The tumor xenograft models used were human non-small cell lung cancer, H520, and …

Sugammadex To Facilitate Neurologic Assessment In Severely Brain-Injured Patients: A Retrospective Analysis And Practical Guidance., Sara J Hyland, Punit A Pandya, Cameron J Mei, David C Yehsakul

Neuroscience Articles

Background Widely used in anesthetic management, sugammadex is increasingly employed in the reversal of neuromuscular blocking agents (NMBAs) in the emergency department and critical care arena, where little evaluative data currently exists. This study explored the utility and safety of using sugammadex to facilitate neurologic assessments in critically ill, NMBA-exposed patients. Methods We pursued a retrospective case series and single-arm cohort analysis of all brain-injured patients receiving sugammadex to facilitate neurologic evaluation during one year at a high-volume Level 1 trauma center. The primary outcome was the qualitative impact of sugammadex administration on neurosurgeon decision-making. Secondary outcomes included the change …

Hdac6 Inhibition Reverses Cisplatin-Induced Mechanical Hypersensitivity Via Tonic Delta Opioid Receptor Signaling, Jixiang Zhang, Jazzmine M Junigan, Ronnie Trinh, Annemieke Kavelaars, Cobi J Heijnen, Peter M Grace

Faculty, Staff and Student Publications

Peripheral neuropathic pain induced by the chemotherapeutic cisplatin can persist for months to years after treatment. Histone deacetylase 6 (HDAC6) inhibitors have therapeutic potential for cisplatin-induced neuropathic pain since they persistently reverse mechanical hypersensitivity and spontaneous pain in rodent models. Here, we investigated the mechanisms underlying reversal of mechanical hypersensitivity in male and female mice by a 2 week treatment with an HDAC6 inhibitor, administered 3 d after the last dose of cisplatin. Mechanical hypersensitivity in animals of both sexes treated with the HDAC6 inhibitor was temporarily reinstated by a single injection of the neutral opioid receptor antagonist 6β-naltrexol or …

Loss Of Activity-Induced Mitochondrial Atp Production Underlies The Synaptic Defects In A Drosophila Model Of Als, Nicholas E Karagas, Richa Gupta, Elham Rastegari, Kai Li Tan, Ho Hang Leung, Hugo J Bellen, Kartik Venkatachalam, Ching-On Wong

Faculty, Staff and Students Publications

Mutations in the gene encoding vesicle-associated membrane protein B (VAPB) cause a familial form of amyotrophic lateral sclerosis (ALS). Expression of an ALS-related variant of vapb (vapb^P58S) in Drosophila motor neurons results in morphologic changes at the larval neuromuscular junction (NMJ) characterized by the appearance of fewer, but larger, presynaptic boutons. Although diminished microtubule stability is known to underlie these morphologic changes, a mechanism for the loss of presynaptic microtubules has been lacking. By studying flies of both sexes, we demonstrate the suppression of vapb^P58S-induced changes in NMJ morphology by either a loss of endoplasmic …

Daphnia As A Sentinel Species For Environmental Health Protection: A Perspective On Biomonitoring And Bioremediation Of Chemical Pollution, Muhammad Abdullahi, Xiaojing Li, Mohamed Abou-Elwafa Abdallah, William Stubbings, Norman Yan, Marianne Barnard, Liang-Hong Guo, John K Colbourne, Luisa Orsini

Faculty, Staff and Student Publications

Despite available technology and the knowledge that chemical pollution damages human and ecosystem health, chemical pollution remains rampant, ineffectively monitored, rarely prevented, and only occasionally mitigated. We present a framework that helps address current major challenges in the monitoring and assessment of chemical pollution by broadening the use of the sentinel species Daphnia as a diagnostic agent of water pollution. And where prevention has failed, we propose the application of Daphnia as a bioremediation agent to help reduce hazards from chemical mixtures in the environment. By applying “omics” technologies to Daphnia exposed to real-world ambient chemical mixtures, we show improvements …

The Mechanisms Of Action Of Tumor Treating Fields, Justin C Moser, Ellaine Salvador, Karina Deniz, Kenneth Swanson, Jack Tuszynski, Kristen W Carlson, Narasimha Kumar Karanam, Chirag B Patel, Michael Story, Emil Lou, Carsten Hagemann

Faculty, Staff and Student Publications

Tumor treating fields (TTFields), a new modality of cancer treatment, are electric fields transmitted transdermally to tumors. The FDA has approved TTFields for the treatment of glioblastoma multiforme and mesothelioma, and they are currently under study in many other cancer types. While antimitotic effects were the first recognized biological anticancer activity of TTFields, data have shown that tumor treating fields achieve their anticancer effects through multiple mechanisms of action. TTFields therefore have the ability to be useful for many cancer types in combination with many different treatment modalities. Here, we review the current understanding of TTFields and their mechanisms of …

Tumor Microenvironment: Barrier Or Opportunity Towards Effective Cancer Therapy, Aadhya Tiwari, Rakesh Trivedi, Shiaw-Yih Lin

Faculty, Staff and Student Publications

Tumor microenvironment (TME) is a specialized ecosystem of host components, designed by tumor cells for successful development and metastasis of tumor. With the advent of 3D culture and advanced bioinformatic methodologies, it is now possible to study TME's individual components and their interplay at higher resolution. Deeper understanding of the immune cell's diversity, stromal constituents, repertoire profiling, neoantigen prediction of TMEs has provided the opportunity to explore the spatial and temporal regulation of immune therapeutic interventions. The variation of TME composition among patients plays an important role in determining responders and non-responders towards cancer immunotherapy. Therefore, there could be a …

Scgwas: Landscape Of Trait-Cell Type Associations By Integrating Single-Cell Transcriptomics-Wide And Genome-Wide Association Studies, Peilin Jia, Ruifeng Hu, Fangfang Yan, Yulin Dai, Zhongming Zhao

Faculty, Staff and Student Publications

BACKGROUND: The rapid accumulation of single-cell RNA sequencing (scRNA-seq) data presents unique opportunities to decode the genetically mediated cell-type specificity in complex diseases. Here, we develop a new method, scGWAS, which effectively leverages scRNA-seq data to achieve two goals: (1) to infer the cell types in which the disease-associated genes manifest and (2) to construct cellular modules which imply disease-specific activation of different processes.

RESULTS: scGWAS only utilizes the average gene expression for each cell type followed by virtual search processes to construct the null distributions of module scores, making it scalable to large scRNA-seq datasets. We demonstrated scGWAS in …

Combined Trip13 And Aurora Kinase Inhibition Induces Apoptosis In Human Papillomavirus-Driven Cancers, Soma Ghosh, Tuhina Mazumdar, Wei Xu, Reid T Powell, Clifford Stephan, Li Shen, Pooja A Shah, Curtis R Pickering, Jeffery N Myers, Jing Wang, Mitchell J Frederick, Faye M Johnson

Faculty, Staff and Student Publications

PURPOSE: Human papillomavirus (HPV) causes >5% of cancers, but no therapies uniquely target HPV-driven cancers.

EXPERIMENTAL DESIGN: We tested the cytotoxic effect of 864 drugs in 16 HPV-positive and 17 HPV-negative human squamous cancer cell lines. We confirmed apoptosis in vitro and in vivo using patient-derived xenografts. Mitotic pathway components were manipulated with drugs, knockdown, and overexpression.

RESULTS: Aurora kinase inhibitors were more effective in vitro and in vivo in HPV-positive than in HPV-negative models. We hypothesized that the mechanism of sensitivity involves retinoblastoma (Rb) expression because the viral oncoprotein E7 leads to Rb protein degradation, and basal Rb protein …

2022 Practice Recommendation Updates From The World Consensus Conference On Bia-Alcl, Fabio Santanelli Di Pompeo, Mark W Clemens, Michael Atlan, Giovanni Botti, Peter G Cordeiro, Daphne De Jong, Arianna Di Napoli, Dennis Hammond, Cara L Haymaker, Steven M Horwitz, Kelly Hunt, Peter Lennox, Patrick Mallucci, Roberto N Miranda, Alexandre M Munhoz, Eric Swanson, Suzanne D Turner, Guido Firmani, Michail Sorotos

Faculty, Staff and Student Publications

BACKGROUND: Laboratory and clinical research on breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is rapidly evolving. Changes in standard of care and insights into best practice were recently presented at the 3rd World Consensus Conference on BIA-ALCL.

OBJECTIVES: The authors sought to provide practice recommendations from a consensus of experts, supplemented with a literature review regarding epidemiology, etiology, pathogenesis, diagnosis, treatment, socio-psychological aspects, and international authority guidance.

METHODS: A literature search of all manuscripts between 1997 and August 2021 for the above areas of BIA-ALCL was conducted with the PubMed database. Manuscripts in different languages, on non-human subjects, and/or discussing …

Public Health Burden Of Secondhand Smoking: Case Reports Of Lung Cancer And A Literature Review, Ladislav Štěpánek, Jarmila Ševčíková, Dagmar Horáková, Mihir Sanjay Patel, Radka Durďáková

Faculty, Staff and Student Publications

Secondhand smoke (SHS), composed of mainstream and sidestream smoke, is a known human carcinogen. It contains a variety of harmful substances at even higher concentrations than mainstream smoke itself, which is inhaled during firsthand smoking. Exposure to SHS, affecting more than a third of the worldwide population, increases the likelihood of lung cancer by roughly 30%, with specific contributions depending on the histological type of cancer. This study aimed to present the harmful potential of SHS through case reports and describe the burden of SHS via a literature review. From a collection of lung cancer case reports occurring in never …

Structural And Functional Diversity Of Type Iv Secretion Systems, Melissa R Cruz, Shane Cristy, Shantanu Guha, Giuseppe Buda De Cesare, Elena Evdokimova, Hiram Sanchez, Dominika Borek, Pedro Miramón, Junko Yano, Paul L Fidel, Alexei Savchenko, David R Andes, Peter J Stogios, Michael C Lorenz, Danielle A Garsin

Faculty, Staff and Student Publications

Fungal pathogens are a continuing challenge due to few effective antifungals and a rise in resistance. In previous work, we described the inhibition of Candida albicans virulence following exposure to the 68 amino acid bacteriocin, EntV, secreted by Enterococcus faecalis. Here, to optimize EntV as a potential therapeutic and better understand its antifungal features, an X-ray structure is obtained. The structure consists of six alpha helices enclosing a seventh 16 amino acid helix (α7). The individual helices are tested for antifungal activity using in vitro and nematode infection assays. Interestingly, α7 retains antifungal, but not antibacterial activity and is also …

Mendelian Gene Identification Through Mouse Embryo Viability Screening, Pilar Cacheiro, Carl Henrik Westerberg, Jesse Mager, Mary E Dickinson, Lauryl M J Nutter, Violeta Muñoz-Fuentes, Chih-Wei Hsu, Ignatia B Van Den Veyver, Ann M Flenniken, Colin Mckerlie, Stephen A Murray, Lydia Teboul, Jason D Heaney, K C Kent Lloyd, Louise Lanoue, Robert E Braun, Jacqueline K White, Amie K Creighton, Valerie Laurin, Ruolin Guo, Dawei Qu, Sara Wells, James Cleak, Rosie Bunton-Stasyshyn, Michelle Stewart, Jackie Harrisson, Jeremy Mason, Hamed Haseli Mashhadi, Helen Parkinson, Ann-Marie Mallon, Damian Smedley

Center for Medical Ethics and Health Policy Staff Publications

Background: The diagnostic rate of Mendelian disorders in sequencing studies continues to increase, along with the pace of novel disease gene discovery. However, variant interpretation in novel genes not currently associated with disease is particularly challenging and strategies combining gene functional evidence with approaches that evaluate the phenotypic similarities between patients and model organisms have proven successful. A full spectrum of intolerance to loss-of-function variation has been previously described, providing evidence that gene essentiality should not be considered as a simple and fixed binary property.

Methods: Here we further dissected this spectrum by assessing the embryonic stage at which homozygous …

Environmental Bacteriophage Detection On Coastal Carolina University Campus, Madison Gentilo, Hailey Oldfield, Gavin Ockert, Paul E. Richardson

Journal of the South Carolina Academy of Science

Bacteriophages are viruses that infect bacteria. These viruses are found ubiquitously in the environment and are more abundant than any living organism on Earth, including bacteria. Eleven sites are designated for weekly sample collection on the campus of Coastal Carolina University. Water samples are filtered and amplified using strains of E. coli B and E. coli K12 to allow potential coliphages in the sample to proliferate to detectable levels. Plaque assays are used as a microbial screen for the presence of bacteriophage. Samples that test positively using the microbial test are analyzed through a molecular test using PCR to identify …

Chronic Stress May Disrupt Covariant Fluctuations Of Vitamin D And Cortisol Plasma Levels And Placentome Formation In Pregnant Sheep During The Last Trimester: A Methodological Approach And Preliminary Report, Colin Wakefield

Tower Health Research Day

No abstract provided.

The Temporal Impulse Response Function In Infantile Nystagmus, Gal Avital, Felicia Kuperwaser, Andrew W Pountain, Keenan A Lacey, Erin E Zwack, Magdalena Podkowik, Bo Shopsin, Victor J Torres, Itai Yanai

Faculty, Staff and Student Publications

Innate immune recognition of bacterial pathogens is a key determinant of the ensuing systemic response, and host or pathogen heterogeneity in this early interaction can impact the course of infection. To gain insight into host response heterogeneity, we investigate macrophage inflammatory dynamics using primary human macrophages infected with Group B Streptococcus. Transcriptomic analysis reveals discrete cellular states within responding macrophages, one of which consists of four sub-states, reflecting inflammatory activation. Infection with six additional bacterial species—Staphylococcus aureus, Listeria monocytogenes, Enterococcus faecalis, Yersinia pseudotuberculosis, Shigella flexneri, and Salmonella enterica—recapitulates these states, though at …

Cue-Induced Cocaine Craving Enhances Psychosocial Stress And Vice Versa In Chronic Cocaine Users, Ann-Kathrin Kexel, Bruno Kluwe-Schiavon, Markus R Baumgartner, Etna J E Engeli, Monika Visentini, Clemens Kirschbaum, Erich Seifritz, Beate Ditzen, Leila M Soravia, Boris B Quednow

Faculty, Staff and Student Publications

Stress and craving, it has been found, contribute to the development and maintenance of and relapse in cocaine use disorder. Chronic cocaine users (CU), previous research has shown, display altered physiological responses to psychosocial stress and increased vegetative responding to substance-related cues. However, how psychosocial stress and cue-induced craving interact in relation to the CU's physiological responses remains largely unknown. We thus investigated the interaction between acute psychosocial stress and cocaine-cue-related reactivity in 47 CU and 38 controls. In a crossed and balanced design, the participants were randomly exposed to a video-based cocaine-cue paradigm and the Trier Social Stress Test …

Maternal Gut Microbiota Mediate Intergenerational Effects Of High-Fat Diet On Descendant Social Behavior, Claudia M Di Gesù, Lisa M Matz, Ian J Bolding, Robert Fultz, Kristi L Hoffman, Antonella Marino Gammazza, Joseph F Petrosino, Shelly A Buffington

Faculty, Staff and Students Publications

Dysbiosis of the maternal gut microbiome during pregnancy is associated with adverse neurodevelopmental outcomes. We previously showed that maternal high-fat diet (MHFD) in mice induces gut dysbiosis, social dysfunction, and underlying synaptic plasticity deficits in male offspring (F1). Here, we reason that, if HFD-mediated changes in maternal gut microbiota drive offspring social deficits, then MHFD-induced dysbiosis in F1 female MHFD offspring would likewise impair F2 social behavior. Metataxonomic sequencing reveals reduced microbial richness among female F1 MHFD offspring. Despite recovery of microbial richness among MHFD-descendant F2 mice, they display social dysfunction. Post-weaning Limosilactobacillus reuteri treatment increases the abundance of short-chain …

Ez Clear For Simple, Rapid, And Robust Mouse Whole Organ Clearing, Chih-Wei Hsu, Juan Cerda, Jason M Kirk, Williamson D Turner, Tara L Rasmussen, Carlos P Flores Suarez, Mary E Dickinson, Joshua D Wythe

Faculty, Staff and Students Publications

Tissue clearing for whole organ cell profiling has revolutionized biology and imaging for exploration of organs in three-dimensional space without compromising tissue architecture. But complicated, laborious procedures, or expensive equipment, as well as the use of hazardous, organic solvents prevent the widespread adoption of these methods. Here, we report a simple and rapid tissue clearing method, EZ Clear, that can clear whole adult mouse organs in 48 hr in just three simple steps. Samples stay at room temperature and remain hydrated throughout the clearing process, preserving endogenous and synthetic fluorescence, without altering sample size. After wholemount clearing and imaging, samples …

Attenuation Of Relapsing Fever Neuroborreliosis In Mice By Il-17a Blockade, Meihui Cheng, Jingwen Xu, Kaiyun Ding, Jing Zhang, Wei Lu, Jiansheng Liu, Jiahong Gao, Kishore R Alugupalli, Hongqi Liu

Department of Microbiology and Immunology Faculty Papers

Relapsing fever due to Borrelia hermsiiis characterized by recurrent bacteremia episodes. However, infection of B. hermsii, if not treated early, can spread to various organs including the central nervous system (CNS). CNS disease manifestations are commonly referred to as relapsing fever neuroborreliosis (RFNB). In the mouse model of B. hermsiiinfection, we have previously shown that the development of RFNB requires innate immune cells as well as T cells. Here, we found that prior to the onset of RFNB, an increase in the systemic proinflammatory cytokine response followed by sustained levels of IP-10 concurrent with the CNS disease phase. RNA sequencing …

Sk3 In Pomc Neurons Plays A Sexually Dimorphic Role In Energy And Glucose Homeostasis, Meng Yu, Jonathan C Bean, Hailan Liu, Yang He, Yongjie Yang, Xing Cai, Kaifan Yu, Zhou Pei, Hesong Liu, Longlong Tu, Kristine M Conde, Mengjie Wang, Yongxiang Li, Na Yin, Nan Zhang, Junying Han, Nikolas A Scarcelli, Pingwen Xu, Yanlin He, Yong Xu, Chunmei Wang

Children’s Nutrition Research Center Staff Publications

Background: Pro-opiomelanocortin (POMC) neurons play a sexually dimorphic role in body weight and glucose balance. However, the mechanisms for the sex differences in POMC neuron functions are not fully understood.

Results: We detected small conductance calcium-activated potassium (SK) current in POMC neurons. Secondary analysis of published single-cell RNA-Seq data showed that POMC neurons abundantly express SK3, one SK channel subunit. To test whether SK3 in POMC neurons regulates POMC neuron functions on energy and glucose homeostasis, we used a Cre-loxP strategy to delete SK3 specifically from mature POMC neurons. POMC-specific deletion of SK3 did not affect body weight in either …

Dissection Of A Sensorimotor Circuit Underlying Pathogen Aversion In C Elegans, Adam Filipowicz, Jonathan Lalsiamthara, Alejandro Aballay

Faculty, Staff and Student Publications

BACKGROUND: Altering animal behavior to reduce pathogen exposure is a key line of defense against pathogen attack. In Caenorhabditis elegans, alterations in intestinal physiology caused by pathogen colonization and sensation of microbial metabolites may lead to activation of pathogen aversive behaviors ranging from aversive reflexes to learned avoidance. However, the neural circuitry between chemosensory neurons that sense pathogenic bacterial cues and the motor neurons responsible for avoidance-associated locomotion remains unknown.

RESULTS: Using C. elegans, we found that backward locomotion was a component of learned pathogen avoidance, as animals pre-exposed to Pseudomonas aeruginosa or Enterococcus faecalis showed reflexive aversion to drops …

Risk Factors For Thoracic Aortic Dissection, Zhen Zhou, Alana C Cecchi, Siddharth K Prakash, Dianna M Milewicz

Faculty, Staff and Student Publications

Thoracic aortic aneurysms involving the root and/or the ascending aorta enlarge over time until an acute tear in the intimal layer leads to a highly fatal condition, an acute aortic dissection (AAD). These Stanford type A AADs, in which the tear occurs above the sinotubular junction, leading to the formation of a false lumen in the aortic wall that may extend to the arch and thoracoabdominal aorta. Type B AADs originate in the descending thoracic aorta just distal to the left subclavian artery. Genetic variants and various environmental conditions that disrupt the aortic wall integrity have been identified that increase …

Infant Behavioral State And Stool Microbiome In Infants Receiving Lactocaseibacillus Rhamnosus Gg In Formula: Randomized Controlled Trial, Robert J Shulman, Maciej Chichlowski, Fabiola Gutierrez Orozco, Cheryl L Harris, Jennifer L Wampler, Nicholas A Bokulich, Carol Lynn Berseth

Faculty, Staff and Students Publications

BACKGROUND: Our aim was to evaluate infant behavioral state, stool microbiome profile and calprotectin in infants with infantile colic receiving a partially hydrolyzed protein formula with or without added Lacticaseibacillus (formerly Lactobacillus) rhamnosus GG (LGG).

METHODS: In this single-center, double-blind, controlled, parallel, prospective study, term infants (14-28 days of age) identified with colic (using modified Wessel's criteria: cried and/or fussed ≥ 3 h/day for ≥ 3 days/week, in a one-week period) were randomized to receive one of two formulas over a three-week feeding period: marketed partially hydrolyzed cow's milk-based infant formula (PHF, n = 35) or a similar formula with …

De Novo Variants In Frmd5 Are Associated With Developmental Delay, Intellectual Disability, Ataxia, And Abnormalities Of Eye Movement, Shenzhao Lu, Mengqi Ma, Xiao Mao, Carlos A Bacino, Joseph Jankovic, V Reid Sutton, James A Bartley, Xueying Wang, Jill A Rosenfeld, Ana Beleza-Meireles, Jaynee Chauhan, Xueyang Pan, Megan Li, Pengfei Liu, Katrina Prescott, Sam Amin, George Davies, Michael F Wangler, Yuwei Dai, Hugo J Bellen

Duncan NRI Faculty and Staff Publications

Proteins containing the FERM (four-point-one, ezrin, radixin, and moesin) domain link the plasma membrane with cytoskeletal structures at specific cellular locations and have been implicated in the localization of cell-membrane-associated proteins and/or phosphoinositides. FERM domain-containing protein 5 (FRMD5) localizes at cell adherens junctions and stabilizes cell-cell contacts. To date, variants in FRMD5 have not been associated with a Mendelian disease in OMIM. Here, we describe eight probands with rare heterozygous missense variants in FRMD5 who present with developmental delay, intellectual disability, ataxia, seizures, and abnormalities of eye movement. The variants are de novo in all for whom parental testing was …