Medicine and Health Sciences Commons^™

Neuraminidase Activity Modulates Cellular Coinfection During Influenza A Virus Multicycle Growth, Zijian Guo, Yuanyuan He, Jian Xu, Ananya N. Benegal, Steven L. Brody, Michael D. Vahey

2020-Current year OA Pubs

Infection of individual cells by multiple virions plays critical roles in the replication and spread of many viruses, but mechanisms that control cellular coinfection during multicycle viral growth remain unclear. Here, we investigate virus-intrinsic factors that control cellular coinfection by influenza A virus (IAV). Using quantitative fluorescence to track the spread of virions from single infected cells, we identify the IAV surface protein neuraminidase (NA) as a key determinant of cellular coinfection. We map this effect to NA's ability to deplete viral receptors from both infected and neighboring uninfected cells. In cases in which viral infectious potential is low, genetic …

Il-11 Induces Nlrp3 Inflammasome Activation In Monocytes And Inflammatory Cell Migration To The Central Nervous System, Maryamsadat Seyedsadr, Tabish H Khan, Ulrike Lorenz, Et Al.

2020-Current year OA Pubs

The objective of this study is to examine IL-11-induced mechanisms of inflammatory cell migration to the central nervous system (CNS). We report that IL-11 is produced at highest frequency by myeloid cells among the peripheral blood mononuclear cell (PBMC) subsets. Patients with relapsing-remitting multiple sclerosis (RRMS) have an increased frequency of IL-11

A Comprehensive Assay Of Social Motivation Reveals Sex-Specific Roles Of Autism-Associated Genes And Oxytocin, Susan E Maloney, Simona Sarafinovska, Claire Weichselbaum, Katherine B Mccullough, Raylynn G Swift, Yating Liu, Joseph D Dougherty

2020-Current year OA Pubs

Social motivation is critical to the development of typical social functioning. Social motivation, specifically one or more of its components (e.g., social reward seeking or social orienting), could be relevant for understanding phenotypes related to autism. We developed a social operant conditioning task to quantify effort to access a social partner and concurrent social orienting in mice. We established that mice will work for access to a social partner, identified sex differences, and observed high test-retest reliability. We then benchmarked the method with two test-case manipulations.

On The Dependent Recognition Of Some Long Zinc Finger Proteins, Zheng Zuo, Timothy Billings, Michael Walker, Petko M Petkov, Polly M Fordyce, Gary D Stormo

2020-Current year OA Pubs

The human genome contains about 800 C2H2 zinc finger proteins (ZFPs), and most of them are composed of long arrays of zinc fingers. Standard ZFP recognition model asserts longer finger arrays should recognize longer DNA-binding sites. However, recent experimental efforts to identify in vivo ZFP binding sites contradict this assumption, with many exhibiting short motifs. Here we use ZFY, CTCF, ZIM3, and ZNF343 as examples to address three closely related questions: What are the reasons that impede current motif discovery methods? What are the functions of those seemingly unused fingers and how can we improve the motif discovery algorithms based …

A List-Mode Multi-Energy Window Low-Count Spect Reconstruction Method For Isotopes With Multiple Emission Peaks, Md Ashequr Rahman, Zekun Li, Zitong Yu, Richard Laforest, Daniel L J Thorek, Abhinav K Jha

2020-Current year OA Pubs

BACKGROUND: Single-photon emission computed tomography (SPECT) provides a mechanism to perform absorbed-dose quantification tasks for [Formula: see text]-particle radiopharmaceutical therapies ([Formula: see text]-RPTs). However, quantitative SPECT for [Formula: see text]-RPT is challenging due to the low number of detected counts, the complex emission spectrum, and other image-degrading artifacts. Towards addressing these challenges, we propose a low-count quantitative SPECT reconstruction method for isotopes with multiple emission peaks.

METHODS: Given the low-count setting, it is important that the reconstruction method extracts the maximal possible information from each detected photon. Processing data over multiple energy windows and in list-mode (LM) format provide mechanisms …

A Simplified Method To Correct Saturation Of Arterial Input Function For Cardiac Magnetic Resonance First-Pass Perfusion Imaging: Validation With Simultaneously Acquired Pet, Ran Li, Masoud Edalati, David Muccigrosso, Jeffrey M C Lau, Richard Laforest, Pamela K Woodard, Jie Zheng

2020-Current year OA Pubs

BACKGROUND: First-pass perfusion imaging in magnetic resonance imaging (MRI) is an established method to measure myocardial blood flow (MBF). An obstacle for accurate quantification of MBF is the saturation of blood pool signal intensity used for arterial input function (AIF). The objective of this project was to validate a new simplified method for AIF estimation obtained from single-bolus and single sequence perfusion measurements. The reference MBF was measured simultaneously on

METHODS: Sixteen patients with clinically confirmed myocardial ischemia were imaged in a clinical whole-body PET-MRI system. PET perfusion imaging was performed in a 10-min acquisition after the injection of 10 …

Heterogeneity In The Effect Of Marked Weight Loss On Metabolic Function In Women With Obesity, Bettina Mittendorfer, Brandon D. Kayser, Mihoko Yoshino, Jun Yoshino, Jeramie D. Watrous, Mohit Jain, J. Christopher Eagon, Bruce W. Patterson, Samuel Klein

2020-Current year OA Pubs

BACKGROUNDThere is considerable heterogeneity in the effect of weight loss on metabolic function in people with obesity.METHODSWe evaluated muscle and liver insulin sensitivity, body composition, and circulating factors associated with insulin action before and after approximately 20% weight loss in women identified as "Responders" (n = 11) or "Non-responders" (n = 11), defined as the top (>75% increase) and bottom (<5% increase) quartiles of the weight loss-induced increase in glucose disposal rate (GDR) during a hyperinsulinemic-euglycemic clamp procedure, among 43 women with obesity (BMI: 44.1 ± 7.9 kg/m2).RESULTSAt baseline, GDR, which provides an index of muscle insulin sensitivity, and the hepatic insulin sensitivity index were more than 50% lower in Responders than Non-responders, but both increased much more after weight loss in Responders than Non-responders, which eliminated the differences between groups. Weight loss also caused greater decreases in intrahepatic triglyceride content and plasma adiponectin and PAI-1 concentrations in Responders than Non-responders and greater insulin-mediated suppression of plasma free fatty acids, branched-chain amino acids, and C3/C5 acylcarnitines in Non-responders than Responders, so that differences between groups at baseline were no longer present after weight loss. The effect of weight loss on total body fat mass, intra-abdominal adipose tissue volume, adipocyte size, and circulating inflammatory markers were not different between groups.CONCLUSIONThe results from our study demonstrate that the heterogeneity in the effects of marked weight loss on muscle and hepatic insulin sensitivity in people with obesity is determined by baseline insulin action, and reaches a ceiling when "normal" insulin action is achieved.TRIAL REGISTRATIONNCT00981500, NCT01299519, NCT02207777.FUNDINGNIH grants P30 DK056341, P30 DK020579, P30 DK052574, UL1 TR002345, and T32 HL13035, the American Diabetes Association (1-18-ICTS-119), the Longer Life Foundation (2019-011), and the Atkins Philanthropic Trust.

Continuous Positive Airway Pressure Increases Csf Flow And Glymphatic Transport, Burhan Ozturk, Sunil Koundal, Ehab Al Bizri, Xinan Chen, Zachary Gursky, Feng Dai, Andrew Lim, Paul Heerdt, Jonathan Kipnis, Allen Tannenbaum, Hedok Lee, Helene Benveniste

2020-Current year OA Pubs

Respiration can positively influence cerebrospinal fluid (CSF) flow in the brain, yet its effects on central nervous system (CNS) fluid homeostasis, including waste clearance function via glymphatic and meningeal lymphatic systems, remain unclear. Here, we investigated the effect of supporting respiratory function via continuous positive airway pressure (CPAP) on glymphatic-lymphatic function in spontaneously breathing anesthetized rodents. To do this, we used a systems approach combining engineering, MRI, computational fluid dynamics analysis, and physiological testing. We first designed a nasal CPAP device for use in the rat and demonstrated that it functioned similarly to clinical devices, as evidenced by its ability …

Structural Specializations Of The Sperm Tail, Miguel Ricardo Leung, Jianwei Zeng, Xiangli Wang, Marc C Roelofs, Wei Huang, Riccardo Zenezini Chiozzi, Johannes F Hevler, Albert J R Heck, Susan K Dutcher, Alan Brown, Rui Zhang, Tzviya Zeev-Ben-Mordehai

2020-Current year OA Pubs

Sperm motility is crucial to reproductive success in sexually reproducing organisms. Impaired sperm movement causes male infertility, which is increasing globally. Sperm are powered by a microtubule-based molecular machine-the axoneme-but it is unclear how axonemal microtubules are ornamented to support motility in diverse fertilization environments. Here, we present high-resolution structures of native axonemal doublet microtubules (DMTs) from sea urchin and bovine sperm, representing external and internal fertilizers. We identify >60 proteins decorating sperm DMTs; at least 15 are sperm associated and 16 are linked to infertility. By comparing DMTs across species and cell types, we define core microtubule inner proteins …

Β Cell Function After Roux-En-Y Gastric Bypass Surgery Or Reduced Energy Intake Alone In People With Obesity, Bettina Mittendorfer, Bruce W. Patterson, Faidon Magkos, Mihoko Yoshino, David P. Bradley, J. Christopher Eagon, Samuel Klein

2020-Current year OA Pubs

BackgroundThe effects of diet-induced weight loss (WL) and WL after Roux-en-Y gastric bypass (RYGB) surgery on β cell function (BCF) are unclear because of conflicting results from different studies, presumably because of differences in the methods used to measure BCF, the amount of WL between treatment groups, and baseline BCF. We evaluated the effect of WL after RYGB surgery or reduced energy intake alone on BCF in people with obesity with and without type 2 diabetes.MethodsBCF (insulin secretion in relationship to plasma glucose) was assessed before and after glucose or mixed-meal ingestion before and after (a) progressive amounts (6%, 11%, …

Defining Diurnal Fluctuations In Mouse Choroid Plexus And Csf At High Molecular, Spatial, And Temporal Resolution, Ryann M Fame, Yong Zhang, Michael J Holtzman, Et Al.

2020-Current year OA Pubs

Transmission and secretion of signals via the choroid plexus (ChP) brain barrier can modulate brain states via regulation of cerebrospinal fluid (CSF) composition. Here, we developed a platform to analyze diurnal variations in male mouse ChP and CSF. Ribosome profiling of ChP epithelial cells revealed diurnal translatome differences in metabolic machinery, secreted proteins, and barrier components. Using ChP and CSF metabolomics and blood-CSF barrier analyses, we observed diurnal changes in metabolites and cellular junctions. We then focused on transthyretin (TTR), a diurnally regulated thyroid hormone chaperone secreted by the ChP. Diurnal variation in ChP TTR depended on Bmal1 clock gene …

Parents' Perspectives On The Utility Of Genomic Sequencing In The Neonatal Intensive Care Unit, Amy A Lemke, Kevin M Bowling, Et Al.

2020-Current year OA Pubs

BACKGROUND: It is critical to understand the wide-ranging clinical and non-clinical effects of genome sequencing (GS) for parents in the NICU context. We assessed parents' experiences with GS as a first-line diagnostic tool for infants with suspected genetic conditions in the NICU.

METHODS: Parents of newborns (N = 62) suspected of having a genetic condition were recruited across five hospitals in the southeast United States as part of the SouthSeq study. Semi-structured interviews (N = 78) were conducted after parents received their child's sequencing result (positive, negative, or variants of unknown significance). Thematic analysis was performed on all interviews.

RESULTS: …

Interplay Between Vsd, Pore, And Membrane Lipids In Electromechanical Coupling In Hcn Channels, Ahmad Elbahnsi, John Cowgill, Verena Burtscher, Linda Wedemann, Luise Zeckey, Baron Chanda, Lucie Delemotte

2020-Current year OA Pubs

Hyperpolarized-activated and cyclic nucleotide-gated (HCN) channels are the only members of the voltage-gated ion channel superfamily in mammals that open upon hyperpolarization, conferring them pacemaker properties that are instrumental for rhythmic firing of cardiac and neuronal cells. Activation of their voltage-sensor domains (VSD) upon hyperpolarization occurs through a downward movement of the S4 helix bearing the gating charges, which triggers a break in the alpha-helical hydrogen bonding pattern at the level of a conserved Serine residue. Previous structural and molecular simulation studies had however failed to capture pore opening that should be triggered by VSD activation, presumably because of a …

Healthy Lifestyle Index And Risk Of Cardiovascular Disease Among Postmenopausal Women With Normal Body Mass Index, Rita Peila, Xiaonan Xue, Qibin Qi, Andrew J Dannenberg, Matthew A Allison, Karen C Johnson, Michael J Lamonte, Robert A Wild, Bernhard Haring, Kathy Pan, Hilary A Tindle, Randi Foraker, Nazmus Saquib, Ana Barac, Thomas E Rohan

2020-Current year OA Pubs

Background A lifestyle comprising a healthy diet, light alcohol consumption, no smoking, and moderate or intense physical activity has been associated with reduced risk of cardiovascular disease (CVD). We examined the association of a healthy lifestyle index (HLI), derived from scores for each of these components plus waist circumference, with the risk of incident CVD and CVD subtypes in postmenopausal women with normal body mass index (18.5-<25.0 kg/m

Striatal Dopamine Synthesis And Cognitive Flexibility Differ Between Hormonal Contraceptive Users And Nonusers, Caitlin M Taylor, Daniella J Furman, Anne S Berry, Robert L White, William J Jagust, Mark D'Esposito, Emily G Jacobs

2020-Current year OA Pubs

In rodents and nonhuman primates, sex hormones are powerful modulators of dopamine (DA) neurotransmission. Yet less is known about hormonal regulation of the DA system in the human brain. Using positron emission tomography (PET), we address this gap by comparing hormonal contraceptive users and nonusers across multiple aspects of DA function: DA synthesis capacity via the PET radioligand 6-[18F]fluoro-m-tyrosine ([18F]FMT), baseline D2/3 receptor binding potential using [11C]raclopride, and DA release using methylphenidate-paired [11C]raclopride. Participants consisted of 36 healthy women (n = 15 hormonal contraceptive users; n = 21 naturally cycling/non users of hormonal contraception), and men (n = 20) as …

Robust Acoustic Trapping And Perturbation Of Single-Cell Microswimmers Illuminate Three-Dimensional Swimming And Ciliary Coordination, Mingyang Cui, Susan K Dutcher, Philip V Bayly, J Mark Meacham

2020-Current year OA Pubs

We report a label-free acoustic microfluidic method to confine single, cilia-driven swimming cells in space without limiting their rotational degrees of freedom. Our platform integrates a surface acoustic wave (SAW) actuator and bulk acoustic wave (BAW) trapping array to enable multiplexed analysis with high spatial resolution and trapping forces that are strong enough to hold individual microswimmers. The hybrid BAW/SAW acoustic tweezers employ high-efficiency mode conversion to achieve submicron image resolution while compensating for parasitic system losses to immersion oil in contact with the microfluidic chip. We use the platform to quantify cilia and cell body motion for wildtype biciliate …

Long-Term Outcomes And Molecular Correlates Of Sotorasib Efficacy In Patients With Pretreated Kras G12c-Mutated Non-Small-Cell Lung Cancer: 2-Year Analysis Of Codebreak 100, Grace K Dy, Ramaswamy Govindan, Et Al.

2020-Current year OA Pubs

No abstract provided.

Use Of Novel Structural Features To Identify Urinary Biomarkers During Acute Kidney Injury That Predict Progression To Chronic Kidney Disease, Jennifer R Charlton, Teng Li, Teresa Wu, Kimberly Deronde, Yanzhe Xu, Edwin J Baldelomar, Kevin M Bennett

2020-Current year OA Pubs

BACKGROUND: A significant barrier to biomarker development in the field of acute kidney injury (AKI) is the use of kidney function to identify candidates. Progress in imaging technology makes it possible to detect early structural changes prior to a decline in kidney function. Early identification of those who will advance to chronic kidney disease (CKD) would allow for the initiation of interventions to halt progression. The goal of this study was to use a structural phenotype defined by magnetic resonance imaging and histology to advance biomarker discovery during the transition from AKI to CKD.

METHODS: Urine was collected and analyzed …

A Review Of Social Media Platform Policies That Address Cannabis Promotion, Marketing And Sales, Carla J Berg, Cassidy R Loparco, Yuxian Cui, Alexandria Pannell, Grace Kong, Lynniah Griffith, Katelyn F Romm, Y Tony Yang, Yan Wang, Patricia A Cavazos-Rehg

2020-Current year OA Pubs

BACKGROUND: Cannabis marketing exposure via social media may impact use in youth and young adults. Most states with recreational cannabis lack policies regarding social media-based marketing. Thus, we examined such policies among prominent platforms, particularly those popular among youth and young adults.

METHODS: In September-October 2022, 3 research team members extracted policies applying to the general community, advertising, and any specific content regarding drug-related content for 11 social media sites: Discord, Facebook, Instagram, Pinterest, Reddit, Snapchat, TikTok, Tumblr, Twitch, Twitter, and YouTube. Using inductive thematic analysis, they then dual-coded restrictions on cannabis-related content (e.g., paid advertising, unpaid promotion, sales). Descriptive …

Social Determinants Of Health And Us Cancer Screening Interventions: A Systematic Review, Ariella R Korn, Callie Walsh-Bailey, Margarita Correa-Mendez, Peter Delnero, Meagan Pilar, Brittney Sandler, Ross C Brownson, Karen M Emmons, April Y Oh

2020-Current year OA Pubs

There remains a need to synthesize linkages between social determinants of health (SDOH) and cancer screening to reduce persistent inequities contributing to the US cancer burden. The authors conducted a systematic review of US-based breast, cervical, colorectal, and lung cancer screening intervention studies to summarize how SDOH have been considered in interventions and relationships between SDOH and screening. Five databases were searched for peer-reviewed research articles published in English between 2010 and 2021. The Covidence software platform was used to screen articles and extract data using a standardized template. Data items included study and intervention characteristics, SDOH intervention components and …

Genetic Deletion Of Skeletal Muscle Ipla2Γ Results In Mitochondrial Dysfunction, Muscle Atrophy And Alterations In Whole-Body Energy Metabolism, Sung Ho Moon, Beverly Gibson Dilthey, Shaoping Guan, Harold F Sims, Sara K Pittman, Amy L Keith, Christopher M Jenkins, Conrad C Weihl, Richard W Gross

2020-Current year OA Pubs

Skeletal muscle is the major site of glucose utilization in mammals integrating serum glucose clearance with mitochondrial respiration. To mechanistically elucidate the roles of iPLA

The Upper And Lower Respiratory Tract Microbiome In Severe Aspiration Pneumonia, Georgios D Kitsios, Janet S Lee, Et Al.

2020-Current year OA Pubs

Uncertainty persists whether anaerobic bacteria represent important pathogens in aspiration pneumonia. In a nested case-control study of mechanically ventilated patients classified as macro-aspiration pneumonia (MAsP, n = 56), non-macro-aspiration pneumonia (NonMAsP, n = 91), and uninfected controls (n = 11), we profiled upper (URT) and lower respiratory tract (LRT) microbiota with bacterial 16S rRNA gene sequencing, measured plasma host-response biomarkers, analyzed bacterial communities by diversity and oxygen requirements, and performed unsupervised clustering with Dirichlet Multinomial Models (DMM). MAsP and NonMAsP patients had indistinguishable microbiota profiles by alpha diversity and oxygen requirements with similar host-response profiles and 60-day survival. Unsupervised DMM …

Treatment Decisions And The Use Of Mek Inhibitors For Children With Neurofibromatosis Type 1-Related Plexiform Neurofibromas, Amy E Armstrong, Allan J Belzberg, John R Crawford, Angela C Hirbe, Zhihong J Wang

2020-Current year OA Pubs

Neurofibromatosis type 1 (NF1), the most common tumor predisposition syndrome, occurs when NF1 gene variants result in loss of neurofibromin, a negative regulator of RAS activity. Plexiform neurofibromas (PN) are peripheral nerve sheath tumors that develop in patients with NF1 and are associated with substantial morbidity and for which, until recently, the only treatment was surgical resection. However, surgery carries several risks and a proportion of PN are considered inoperable. Understanding the genetic underpinnings of PN led to the investigation of targeted therapies as medical treatment options, and the MEK1/2 inhibitor selumetinib has shown promising efficacy in pediatric patients with …

Personalized [177lu]Lutetium-Psma Therapy For Patients With Pre-Treated Castration-Resistant Prostate Cancer: A Single Institution Experience From A Comprehensive Cancer Centre, Wolfgang Thaiss, Friedemann Zengerling, Julia Friedrich, Veronika Hechler, Michael Grunert, Christian Bolenz, Thomas Wiegel, Ambros J Beer, Vikas Prasad

2020-Current year OA Pubs

Castration resistant prostate cancer (CRPC) is characterized by an aggressive biological behavior with a relatively short survival time, especially in progressive tumors pretreated with new hormonal agents and taxane chemotherapy. [177Lu]-Lutetium-PSMA (Lu-PSMA) treatment has proven efficacy in these patients. However, around 30% of the CRPC patients do not benefit from Lu-PSMA treatment, and little is known about predictive factors for treatment success if Lu-PSMA is offered in an individualized approach based on clinical and laboratory features. In this monocentric retrospective study, 86 CRPC patients receiving Lu-PSMA treatment were evaluated. The focus of the study was to describe clinical factors at …

Comprehensive Functional Characterization Of Sgcb Coding Variants Predicts Pathogenicity In Limb-Girdle Muscular Dystrophy Type R4/2e, Chengcheng Li, Jackson Wilborn, Sara Pittman, Jil Daw, Jorge Alonso-Pérez, Jordi Díaz-Manera, Conrad C. Weihl, Gabe Haller

2020-Current year OA Pubs

Genetic testing is essential for patients with a suspected hereditary myopathy. More than 50% of patients clinically diagnosed with a myopathy carry a variant of unknown significance in a myopathy gene, often leaving them without a genetic diagnosis. Limb-girdle muscular dystrophy (LGMD) type R4/2E is caused by mutations in β-sarcoglycan (SGCB). Together, β-, α-, γ-, and δ-sarcoglycan form a 4-protein transmembrane complex (SGC) that localizes to the sarcolemma. Biallelic loss-of-function mutations in any subunit can lead to LGMD. To provide functional evidence for the pathogenicity of missense variants, we performed deep mutational scanning of SGCB and assessed SGC cell surface …

Polypill Eligibility For Patients With Heart Failure With Reduced Ejection Fraction In The Asian-Hf Registry: A Cross-Sectional Analysis, Aishwarya Vijay, Wan Ting Tay, Tiew-Hwa K. Teng, Kanako Teramoto, Jasper Tromp, Wouter Ouwerkerk, Seet Yoong Lo, Wataru Shimizu, Mark D. Huffman, Carolyn S P Lam, Chanchal Chandramouli, Anubha Agarwal

2020-Current year OA Pubs

BACKGROUND: The rates of guideline-directed medical therapy (GDMT) prescription for heart failure with reduced ejection fraction (HFrEF) in Asia remain sub-optimal. The primary objective of this study was to examine HFrEF polypill eligibility in the context of measured baseline prescription rates of individual components of GDMT among participants with HFrEF in Asia.

METHODS: A retrospective analysis of 4,868 patients with HFrEF from the multi-national ASIAN-HF registry was performed, and 3,716 patients were included in the final, complete case analysis. Eligibility for a HFrEF polypill, upon which patients were grouped and characterized, was based on the following: left ventricular systolic dysfunction …

A Refined, Controlled 16s Rrna Gene Sequencing Approach Reveals Limited Detection Of Cerebrospinal Fluid Microbiota In Children With Bacterial Meningitis, Christopher E. Pope, Kathryn B. Whitlock, Paul Hodor, David D. Limbrick Jr, Patrick J. Mcdonald, Jason Hauptman, Lucas R Hoffman, Tamara D. Simon

2020-Current year OA Pubs

Advances in both laboratory and computational components of high-throughput 16S amplicon sequencing (16S HTS) have markedly increased its sensitivity and specificity. Additionally, these refinements have better delineated the limits of sensitivity, and contributions of contamination to these limits, for 16S HTS that are particularly relevant for samples with low bacterial loads, such as human cerebrospinal fluid (CSF). The objectives of this work were to (i) optimize the performance of 16S HTS in CSF samples with low bacterial loads by defining and addressing potential sources of error, and (ii) perform refined 16S HTS on CSF samples from children diagnosed with bacterial …

Gene Therapy Ameliorates Spontaneous Seizures Associated With Cortical Neuron Loss In A Cln2r207x Mouse Model, Keigo Takahashi, Elizabeth M. Eultgen, Sophie H. Wang, Nicholas R. Rensing, Hemanth R. Nelvagal, Joshua T. Dearborn, Olivier Danos, Nicholas Buss, Mark S. Sands, Michael Wong, Jonathan D. Cooper

2020-Current year OA Pubs

Although a disease-modifying therapy for classic late infantile neuronal ceroid lipofuscinosis (CLN2 disease) exists, poor understanding of cellular pathophysiology has hampered the development of more effective and persistent therapies. Here, we investigated the nature and progression of neurological and underlying neuropathological changes in Cln2R207X mice, which carry one of the most common pathogenic mutations in human patients but are yet to be fully characterized. Long-term electroencephalography recordings revealed progressive epileptiform abnormalities, including spontaneous seizures, providing a robust, quantifiable, and clinically relevant phenotype. These seizures were accompanied by the loss of multiple cortical neuron populations, including those stained for interneuron markers. …

Antigen-Driven Colonic Inflammation Is Associated With Development Of Dysplasia In Primary Sclerosing Cholangitis, Dustin G Shaw, Kelly Monroe, Rodney Newberry, Et Al.

2020-Current year OA Pubs

Primary sclerosing cholangitis (PSC) is an immune-mediated disease of the bile ducts that co-occurs with inflammatory bowel disease (IBD) in almost 90% of cases. Colorectal cancer is a major complication of patients with PSC and IBD, and these patients are at a much greater risk compared to patients with IBD without concomitant PSC. Combining flow cytometry, bulk and single-cell transcriptomics, and T and B cell receptor repertoire analysis of right colon tissue from 65 patients with PSC, 108 patients with IBD and 48 healthy individuals we identified a unique adaptive inflammatory transcriptional signature associated with greater risk and shorter time …

Evaluation Of The Ng-Test Carba 5 Lateral Flow Assay With An Imp-2-Producing Morganella Morganii And Other Morganellaceae, Nicole J. Tarlton, Meghan A. Wallace, Robert F. Potter, Kailun Zhang, Gautam Dantas, Erik R. Dubberke, Carey-Ann D. Burnham, Melanie L. Yarbrough

2020-Current year OA Pubs

An isolate of Morganella morganii (MMOR1) that tested susceptible to 3