Medical Microbiology Commons^™

The Evolution And Structure/Function Of Bhlh-Pas Transcription Factor Family, Hailey E Edwards, Daniel A Gorelick

Faculty, Staff and Students Publications

Proteins that contain basic helix-loop-helix (bHLH) and Per-Arnt-Sim motifs (PAS) function as transcription factors. bHLH-PAS proteins exhibit essential and diverse functions throughout the body, from cell specification and differentiation in embryonic development to the proper function of organs like the brain and liver in adulthood. bHLH-PAS proteins are divided into two classes, which form heterodimers to regulate transcription. Class I bHLH-PAS proteins are typically activated in response to specific stimuli, while class II proteins are expressed more ubiquitously. Here, we discuss the general structure and functions of bHLH-PAS proteins throughout the animal kingdom, including family members that do not fit …

Presence Of Blaper-1 And Blaveb-1 Beta-Lactamase Genes Among Isolates Of Pseudomonas Aeruginosa From Burn And Trauma Hospital Peshawar, Pakistan, Suleman Khan, Samiyah Tasleem, Alfarah Rehmat Ullah,, Sarwat Moon, Saad Alghamdi, Raina Saad Suliman, Muhammad Ateeq, Muhmmad Salman, Anas S. Dablool,, Banan Atwah, Farkad Bantun

Journal of Bioresource Management

Pseudomonas aeruginosa spp are the most prevalent bacteria that cause nosocomial infections in hospitals. Most antibiotics, including novel new β-lactams, are already resistant to them, and they can become resistant during treatment, which can make the treatment fail. P. aeruginosa isolates from ICU patients who had Per-1 and VEB-1 were the main focus of this study. These two ESBLs are the two most common in ICU patients who had them. 50 isolates were gathered from Peshawar's LRH ICU facilities in the year 2021. The antibiotic susceptibility test was conducted in accordance with the Clinical and Laboratory Standards Institute's standards (CLSI). …

Dietary Fatty Acid Intake And The Colonic Gut Microbiota In Humans, Anthony A Xu, Luke K Kennedy, Kristi Hoffman, Donna L White, Fasiha Kanwal, Hashem B El-Serag, Joseph F Petrosino, Li Jiao

Faculty, Staff and Students Publications

A high-fat diet has been associated with systemic diseases in humans and alterations in gut microbiota in animal studies. However, the influence of dietary fatty acid intake on gut microbiota in humans has not been well studied. In this cross-sectional study, we examined the association between intake of total fatty acids (TFAs), saturated fatty acids (SFAs), trans fatty acids (TrFAs), monounsaturated fatty acids (MUFAs), polyunsaturated fatty acids (PUFAs), n3-FAs, and n6-FAs, and the community composition and structure of the adherent colonic gut microbiota. We obtained 97 colonic biopsies from 34 participants with endoscopically normal colons. Microbial DNA was used to …

Mycn-Driven Fatty Acid Uptake Is A Metabolic Vulnerability In Neuroblastoma, Ling Tao, Mahmoud A Mohammad, Giorgio Milazzo, Myrthala Moreno-Smith, Tajhal D Patel, Barry Zorman, Andrew Badachhape, Blanca E Hernandez, Amber B Wolf, Zihua Zeng, Jennifer H Foster, Sara Aloisi, Pavel Sumazin, Youli Zu, John Hicks, Ketan B Ghaghada, Nagireddy Putluri, Giovanni Perini, Cristian Coarfa, Eveline Barbieri

Faculty, Staff and Students Publications

Neuroblastoma (NB) is a childhood cancer arising from sympatho-adrenal neural crest cells. MYCN amplification is found in half of high-risk NB patients; however, no available therapies directly target MYCN. Using multi-dimensional metabolic profiling in MYCN expression systems and primary patient tumors, we comprehensively characterized the metabolic landscape driven by MYCN in NB. MYCN amplification leads to glycerolipid accumulation by promoting fatty acid (FA) uptake and biosynthesis. We found that cells expressing amplified MYCN depend highly on FA uptake for survival. Mechanistically, MYCN directly upregulates FA transport protein 2 (FATP2), encoded by SLC27A2. Genetic depletion of SLC27A2 impairs NB survival, and …

Genomic Features Underlie The Co-Option Of Sva Transposons As Cis-Regulatory Elements In Human Pluripotent Stem Cells, Samantha M Barnada, Andrew Isopi, Daniela Tejada-Martinez, Clément Goubert, Sruti Patoori, Luca Pagliaroli, Mason Tracewell, Marco Trizzino

Department of Biochemistry and Molecular Biology Faculty Papers

Domestication of transposable elements (TEs) into functional cis-regulatory elements is a widespread phenomenon. However, the mechanisms behind why some TEs are co-opted as functional enhancers while others are not are underappreciated. SINE-VNTR-Alus (SVAs) are the youngest group of transposons in the human genome, where ~3,700 copies are annotated, nearly half of which are human-specific. Many studies indicate that SVAs are among the most frequently co-opted TEs in human gene regulation, but the mechanisms underlying such processes have not yet been thoroughly investigated. Here, we leveraged CRISPR-interference (CRISPRi), computational and functional genomics to elucidate the genomic features that underlie SVA domestication …

How Irish Medical Scientists Can Assist In The Improved Diagnosis Of The Disease Infectious Mononucleosis, Patrick Naughton

ORBioM (Open Research BioSciences Meeting)

Background:

The eponymously named Epstein-Barr Virus (EBV) or human herpesvirus 4 (HHV-4) is the sole causative agent of the acute illness in humans described either as infectious mononucleosis (IM), or glandular fever. IM, when not clinically silent, can present in patients with at least two of the classic triad of symptoms of fever, pharyngitis, and lymphadenopathy. Challenges for the clinician arise when atypical cases present. Early, accurate and informed laboratory test results are vital for diagnosis, appropriate treatment, and patient management. A key challenge for the practitioner, particularly in cases where the illness can present atypically, is distinguishing bacterial tonsillitis …

Effect Of Sub-Inhibitory Concentrations Of Nitrofurantoin, Ciprofloxacin And Trimethoprim On In-Vitro Biofilm Formation In Uropathogenic Escherichia Coli, Shane Whelan

ORBioM (Open Research BioSciences Meeting)

The purpose of the current study was to determine the effect of sublethal concentrations of nitrofurantoin, ciprofloxacin and trimethoprim on biofilm formation in 57 uropathogenic Escherichia coli strains (UPEC).

The MIC of nitrofurantoin, ciprofloxacin and trimethoprim was determined for 57 UPEC isolates. Biofilm formation for each isolate with and without sub-lethal concentrations of each antibiotic was then quantified, and the statistical significance of changes in biofilm formation was ascertained by way of a Dunnett's test.

The effects of sub-MIC antibiotics on biofilm formation of UPEC were variable. A total of 22.8% of strains were induced to form biofilm by nitrofurantoin, …

Temporal Changes In Gastrointestinal Fungi And The Risk Of Autoimmunity During Early Childhood: The Teddy Study, Thomas A Auchtung, Christopher J Stewart, Daniel P Smith, Eric W Triplett, Daniel Agardh, William A Hagopian, Anette G Ziegler, Marian J Rewers, Jin-Xiong She, Jorma Toppari, Åke Lernmark, Beena Akolkar, Jeffrey P Krischer, Kendra Vehik, Jennifer M Auchtung, Nadim J Ajami, Joseph F Petrosino

Faculty, Staff and Students Publications

Fungal infections are a major health problem that often begin in the gastrointestinal tract. Gut microbe interactions in early childhood are critical for proper immune responses, yet there is little known about the development of the fungal population from infancy into childhood. Here, as part of the TEDDY (The Environmental Determinants of Diabetes in the Young) study, we examine stool samples of 888 children from 3 to 48 months and find considerable differences between fungi and bacteria. The metagenomic relative abundance of fungi was extremely low but increased while weaning from milk and formula. Overall fungal diversity remained constant over …

Inflammatory Diseases And Resections Of The Digestive Tract Influence The Risk Of Circulating Food-Specific-Igg, Jacques Izard, Walker Carson, Joseph Baumert, Jennifer Clarke

Department of Food Science and Technology: Faculty Publications

Objectives: Individuals affected with inflammatory diseases of the digestive tract or have had surgical removal of sections of the digestive tract are often in need to adjust their diet. The symptomatology associated with food intake issues is often informally reported as food sensitivity. We investigated the circulating food-specific-IgG among ten conditions.

Conclusion: The risk of the having circulating food-specific IgG differed widely among the conditions investigated. The maintenance of a colonic environment might influence the risk of food sensitivity in ostomates.

Pdxnet Portal: Patient-Derived Xenograft Model, Data, Workflow And Tool Discovery, Soner Koc, Michael W Lloyd, Jeffrey W Grover, Nan Xiao, Sara Seepo, Sai Lakshmi Subramanian, Manisha Ray, Christian Frech, John Digiovanna, Phillip Webster, Steven Neuhauser, Anuj Srivastava, Xing Yi Woo, Brian J Sanderson, Brian White, Paul Lott, Lacey E Dobrolecki, Heidi Dowst, Pdxnet Consortium;, Yvonne A Evrard, Tiffany A Wallace, Jeffrey A Moscow, James H Doroshow, Nicholas Mitsiades, Salma Kaochar, Chong-Xian Pan, Moon S Chen, Luis Carvajal-Carmona, Alana L Welm, Bryan E Welm, Michael T Lewis, Ramaswamy Govindan, Li Ding, Shunqiang Li, Meenhard Herlyn, Michael A Davies, Jack Roth, Funda Meric-Bernstam, Peter N Robinson, Carol J Bult, Brandi Davis-Dusenbery, Dennis A Dean, Jeffrey H Chuang

Faculty, Staff and Students Publications

We created the PDX Network (PDXNet) portal (https://portal.pdxnetwork.org/) to centralize access to the National Cancer Institute-funded PDXNet consortium resources, to facilitate collaboration among researchers and to make these data easily available for research. The portal includes sections for resources, analysis results, metrics for PDXNet activities, data processing protocols and training materials for processing PDX data. Currently, the portal contains PDXNet model information and data resources from 334 new models across 33 cancer types. Tissue samples of these models were deposited in the NCI's Patient-Derived Model Repository (PDMR) for public access. These models have 2134 associated sequencing files from 873 samples …

Skin Fibrosis And Recovery Is Dependent On Wnt Activation Via Dpp4, Anna R Jussila, Brian Zhang, Elizabeth Caves, Sakin Kirti, Miarasa Steele, Emily Hamburg-Shields, John Lydon, Yan Ying, Robert Lafyatis, Sanjay Rajagopalan, Valerie Horsley, Radhika P Atit

Faculty, Staff and Students Publications

Fibrosis is the life-threatening, excessive accumulation of the extracellular matrix and is sometimes associated with a loss of lipid-filled cells in the skin and other organs. Understanding the mechanisms of fibrosis and associated lipodystrophy and their reversal may reveal new targets for therapeutic intervention. In vivo genetic models are needed to identify key targets that induce recovery from established fibrosis. Wnt signaling is activated in animal and human fibrotic diseases across organs. Here, we developed a genetically inducible and reversible Wnt activation model and showed that it is sufficient to cause fibrotic dermal remodeling, including extracellular matrix expansion and shrinking …

Aberrant Uterine Folding In Mice Disrupts Implantation Chamber Formation And Alignment Of Embryo-Uterine Axes, Manoj K Madhavan, Francesco J Demayo, John P Lydon, Niraj R Joshi, Asgerally T Fazleabas, Ripla Arora

Faculty, Staff and Students Publications

The uterine luminal epithelium folds characteristically in mammals, including humans, horses and rodents. Improper uterine folding in horses results in pregnancy failure, but the precise function of folds remains unknown. Here, we uncover dynamic changes in the 3D uterine folding pattern during early pregnancy with the entire lumen forming pre-implantation transverse folds along the mesometrial-antimesometrial axis. Using a time course, we show that transverse folds are formed before embryo spacing, whereas implantation chambers form as the embryo begins attachment. Thus, folds and chambers are two distinct structures. Transverse folds resolve to form a flat implantation region, after which an embryo …

Discovery Of The First Lyticstaphylococcus Pseudintermedius/ Staphylococcus Aureus Polyvalent Bacteriophages, Haroldo Hernandez Santos, Justin Clark, Austen Terwilliger, Anthony Maresso

Faculty, Staff and Students Publications

Background:

There are no verified lytic Staphylococcus pseudintermedius phages in the literature and few temperate phage genomes in databases. S. pseudintermedius is an opportunistic zoonotic pathogen of great importance in veterinary and human medicine.

Materials and Methods:

We discovered phages against canine-derived S. pseudintermedius isolates by screening dog feces, hair, and skin swabs. Fourteen new phages were isolated and characterized by genomic analysis, transmission electron microscopy, and host range determination.

Results:

Three phages—DH2, DH5, and DS10, a phage K variant—were predicted lytic by sequencing, a designation supported by mitomycin C induction. All three are S. pseudintermedius and Staphylococcus aureus polyvalent …

A Case Report Of Pulmonary Actinomycosis: A Diagnostic Quagmire, Sarah Akbani, Aderinsola O. Ademiluyi, Jonathan Dean, Vinita Mathur

Advances in Clinical Medical Research and Healthcare Delivery

The implications of misdiagnosis can be drastic, especially when the correct diagnosis is treatable. Pulmonary actinomycosis is one of the complications of infection with actinomyces, an anaerobic gram-positive organism that is usually found as a part of the normal flora in the human body infection. It is a very rare disease and is frequently mistaken with other diagnoses owing to its nonspecific presentation. In this report, we present a 67-year-old male with a mass like lesion on a CT scan of his chest that was done due to progressively worsening productive cough, weight loss and fatigue. These symptoms could have …

A Single Dose Of The Deactivated Rabies-Virus Vectored Covid-19 Vaccine, Coravax, Is Highly Efficacious And Alleviates Lung Inflammation In The Hamster Model, Drishya Kurup, Christoph Wirblich, Leila Zabihi Diba, Rachael Lambert, Megan Watson, Noor Shaikh, Holly Ramage, Charalambos Solomides, Matthias J Schnell

Department of Microbiology and Immunology Faculty Papers

Without sufficient herd immunity through either vaccination or natural infection, the coronavirus disease 2019 pandemic is unlikely to be controlled. Waning immunity with the currently approved vaccines suggests the need to evaluate vaccines causing the induction of long-term responses. Here, we report the immunogenicity and efficacy of our adjuvanted single-dose Rabies-vectored SARS-CoV-2 S1 vaccine, CORAVAX, in hamsters. CORAVAX induces high SARS-CoV-2 S1-specific and virus-neutralizing antibodies (VNAs) that prevent weight loss, viral loads, disease, lung inflammation, and the cytokine storm in hamsters. We also observed high Rabies VNA titers. In summary, CORAVAX is a promising dual-antigen vaccine candidate for clinical evaluation …

Identification Of Multiple Hub Genes In Acute Kidney Injury After Kidney Transplantation By Bioinformatics Analysis, Sang Wook Kang, Sung Wook Kang, Ju Yeon Ban, Min Su Park

School of Graduate Studies Faculty Publications

Background and Objectives: The molecular mechanisms of the development of acute kidney injury (AKI) after kidney transplantation are not yet clear. The aim of this study was to confirm the genes and mechanisms related to AKI after transplantation. Materials and Methods: To investigate potential genetic targets for AKI, an analysis of the gene expression omnibus database was used to identify key genes and pathways. After identification of differentially expressed genes, Kyoto En-cyclopedia of Genes and Genome pathway enrichment analyses were performed. We identified the hub genes and established the protein–protein interaction network. Results: Finally, we identified 137 differentially expressed genes …

Cathelicidin Anti-Microbial Peptide (Camp) Is Toxic During Neonatal Influenza Virus Infection, Nneka Ugwu

St. Chris Research Day

No abstract provided.

Concerted Type I Interferon Signaling In Microglia And Neural Cells Promotes Memory Impairment Associated With Amyloid Β Plaques, Ethan R Roy, Gabriel Chiu, Sanming Li, Nicholas E Propson, Rupa Kanchi, Baiping Wang, Cristian Coarfa, Hui Zheng, Wei Cao

Faculty, Staff and Students Publications

The principal signals that drive memory and cognitive impairment in Alzheimer's disease (AD) remain elusive. Here, we revealed brain-wide cellular reactions to type I interferon (IFN-I), an innate immune cytokine aberrantly elicited by amyloid β plaques, and examined their role in cognition and neuropathology relevant to AD in a murine amyloidosis model. Using a fate-mapping reporter system to track cellular responses to IFN-I, we detected robust, Aβ-pathology-dependent IFN-I activation in microglia and other cell types. Long-term blockade of IFN-I receptor (IFNAR) rescued both memory and synaptic deficits and resulted in reduced microgliosis, inflammation, and neuritic pathology. Microglia-specific Ifnar1 deletion attenuated …

The Ep300/Tp53 Pathway, A Suppressor Of The Hippo And Canonical Wnt Pathways, Is Activated In Human Hearts With Arrhythmogenic Cardiomyopathy In The Absence Of Overt Heart Failure, Leila Rouhi, Siyang Fan, Sirisha M Cheedipudi, Aitana Braza-Boïls, Maria Sabater Molina, Yan Yao, Matthew J Robertson, Cristian Coarfa, Juan R Gimeno, Pilar Molina, Priyatansh Gurha, Esther Zorio, Ali J Marian

Faculty, Staff and Students Publications

AIMS: Arrhythmogenic cardiomyopathy (ACM) is a primary myocardial disease that typically manifests with cardiac arrhythmias, progressive heart failure, and sudden cardiac death (SCD). ACM is mainly caused by mutations in genes encoding desmosome proteins. Desmosomes are cell-cell adhesion structures and hubs for mechanosensing and mechanotransduction. The objective was to identify the dysregulated molecular and biological pathways in human ACM in the absence of overt heart failure.

METHODS AND RESULTS: Transcriptomes in the right ventricular endomyocardial biopsy samples from three independent individuals carrying truncating mutations in the DSP gene and five control samples were analysed by RNA-Seq (discovery group). These cases …

Intraovarian, Isoform-Specific Transcriptional Roles Of Progesterone Receptor In Ovulation, Kirsten M Smith, Doan T Dinh, Lisa K Akison, Matilda Nicholls, Kylie R Dunning, Atsushi Morimoto, John P Lydon, Darryl L Russell, Rebecca L Robker

Faculty, Staff and Students Publications

Progesterone receptor (PGR) activity is obligatory for mammalian ovulation; however, there is no established direct functional pathway explaining how progesterone receptor completely and specifically regulates oocyte release. This study examined the overarching cell- and isoform-specific effects of the PGR within each cellular compartment of the ovary, using mice null for the PGR (PRKO), as well as isoform-specific null mice. The PGR was expressed in ovarian granulosa and stromal cells and although PRKO ovaries showed no visible histological changes in preovulatory ovarian morphology, follicle rupture did not occur. Reciprocal ovarian transplant experiments established the necessity of ovarian PGR expression for ovulation. …

Maternal Antepartum Administration Of Lactoferrin Ameliorates Neonatal Infection By Bacteremia-Producing Escherichia Coli In Mice, Charity Dunlop

Research Days

Background: E. coli is a major cause of neonatal sepsis. Vaginal pathogenic E. coli strains ascend into the pregnant uterus infecting the offspring of colonized mothers. Lactoferrin (LF) is an antibacterial and immunomodulatory glycoprotein that has been given to preterm newborns to prevent lateonset sepsis. However, the effects of maternal LF administration to prevent neonatal E. coli invasive infection have not been studied.

Objectives/Goal: Our goal was to test the hypothesis that LF pre-treatment of pregnant mice administered prenatally will significantly reduce the bacterial load in their embryos following infection with E. coli.

Methods/Design: Human LF 100 mcg/mL or placebo …

Systems Biology Approach To Functionally Assess The Clostridioides Difficile Pangenome Reveals Genetic Diversity With Discriminatory Power, Charles J Norsigian, Heather A Danhof, Colleen K Brand, Firas S Midani, Jared T Broddrick, Tor C Savidge, Robert A Britton, Bernhard O Palsson, Jennifer K Spinler, Jonathan M Monk

Faculty, Staff and Students Publications

Combatting Clostridioides difficile infections, a dominant cause of hospital-associated infections with incidence and resulting deaths increasing worldwide, is complicated by the frequent emergence of new virulent strains. Here, we employ whole-genome sequencing, high-throughput phenotypic screenings, and genome-scale models of metabolism to evaluate the genetic diversity of 451 strains of C. difficile. Constructing the C. difficile pangenome based on this set revealed 9,924 distinct gene clusters, of which 2,899 (29%) are defined as core, 2,968 (30%) are defined as unique, and the remaining 4,057 (41%) are defined as accessory. We develop a strain typing method, sequence typing by accessory genome (STAG), …

Extracellular Vesicles Released After Cranial Radiation: An Insight Into An Early Mechanism Of Brain Injury., Suriyan Sukati, Jenni Ho, Luksana Chaiswing, Pradoldej Sompol, Harshul Pandit, Wendy Wei, Tadahide Izumi, Quan Chen, Heidi Weiss, Teresa Noel, Subbarao Bondada, D Allan Butterfield, Daret K St Clair

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Cranial radiation is important for treating both primary brain tumors and brain metastases. A potential delayed side effect of cranial radiation is neurocognitive function decline. Early detection of CNS injury might prevent further neuronal damage. Extracellular vesicles (EVs) have emerged as a potential diagnostic tool because of their unique membranous characteristics and cargos. We investigated whether EVs can be an early indicator of CNS injury by giving C57BJ/6 mice 10 Gy cranial IR. EVs were isolated from sera to quantify: 1) number of EVs using nanoparticle tracking analysis (NTA); 2) Glial fibrillary acidic protein (GFAP), an astrocyte marker; and 3) …

Identification Of Ciprofloxacin Resistance Factors Via In Vivo Evolution Of Aeromonas Veronii In The Medicinal Leech, Lauren Daddi

Honors Scholar Theses

Infections from ciprofloxacin (Cp) resistant (Cp^R) Aeromonas veronii have been reported in increasing numbers among patients receiving leech therapy in recent years. Mutations in DNA gyrase, gyrA S83I, and DNA topoisomerase IV, parC E91K, along with acquisition of the qnrS2 gene located on the pAv42 plasmid, have been identified as genetic factors contributing to Cp^R in A. veronii. A strain of A. veronii harboring all known resistance factors was previously constructed and has a Cp minimum inhibitory concentration (MIC) of 3 µg/ml, which remains below the resistance threshold of 4 µg/ml and well below the high …

Phgdh Heterogeneity Potentiates Cancer Cell Dissemination And Metastasis, Matteo Rossi, Patricia Altea-Manzano, Margherita Demicco, Ginevra Doglioni, Laura Bornes, Marina Fukano, Anke Vandekeere, Alejandro M Cuadros, Juan Fernández-García, Carla Riera-Domingo, Cristina Jauset, Mélanie Planque, H Furkan Alkan, David Nittner, Dongmei Zuo, Lindsay A Broadfield, Sweta Parik, Antonino Alejandro Pane, Francesca Rizzollo, Gianmarco Rinaldi, Tao Zhang, Shao Thing Teoh, Arin B Aurora, Panagiotis Karras, Ines Vermeire, Dorien Broekaert, Joke Van Elsen, Maximilian M L Knott, Martin F Orth, Sofie Demeyer, Guy Eelen, Lacey E Dobrolecki, Ayse Bassez, Thomas Van Brussel, Karl Sotlar, Michael T Lewis, Harald Bartsch, Manfred Wuhrer, Peter Van Veelen, Peter Carmeliet, Jan Cools, Sean J Morrison, Jean-Christophe Marine, Diether Lambrechts, Massimiliano Mazzone, Gregory J Hannon, Sophia Y Lunt, Thomas G P Grünewald, Morag Park, Jacco Van Rheenen, Sarah-Maria Fendt

Faculty, Staff and Students Publications

Cancer metastasis requires the transient activation of cellular programs enabling dissemination and seeding in distant organs1. Genetic, transcriptional and translational heterogeneity contributes to this dynamic process2,3. Metabolic heterogeneity has also been observed4, yet its role in cancer progression is less explored. Here, we discover that loss of phosphoglycerate dehydrogenase (PHGDH) potentiates metastatic dissemination. Specifically, we find that heterogeneous or low PHGDH expression in primary tumors of breast cancer patients is associated with decreased metastasis free survival time. In mice, circulating tumor cells and early metastatic lesions are enriched with PHGDH low cancer …

The Disordered N-Terminal Domain Of Dnmt3a Recognizes H2ak119ub And Is Required For Postnatal Development, Tianpeng Gu, Dapeng Hao, Junsung Woo, Teng-Wei Huang, Lei Guo, Xueqiu Lin, Anna G Guzman, Ayala Tovy, Carina Rosas, Mira Jeong, Yubin Zhou, Benjamin Deneen, Yun Huang, Wei Li, Margaret A Goodell

Faculty, Staff and Students Publications

DNA methyltransferase 3a (DNMT3A) plays a crucial role during mammalian development. Two isoforms of DNMT3A are differentially expressed from stem cells to somatic tissues, but their individual functions remain largely uncharacterized. Here we report that the long isoform DNMT3A1, but not the short DNMT3A2, is essential for mouse postnatal development. DNMT3A1 binds to and regulates bivalent neurodevelopmental genes in the brain. Strikingly, Dnmt3a1 knockout perinatal lethality could be partially rescued by DNMT3A1 restoration in the nervous system. We further show that the intrinsically disordered N terminus of DNMT3A1 is required for normal development and DNA methylation at DNMT3A1-enriched regions. Mechanistically, …

Editorial: Mucosal Vaccination: Strategies To Induce And Evaluate Mucosal Immunity, Pamela A. Kozlowski, Nicholas J. Mantis, Andreas Frey

School of Medicine Faculty Publications

No abstract provided.

Antiviral Activity Of Olanexidine-Containing Hand Rub Against Human Noroviruses, Khalil Ettayebi, Wilhelm Salmen, Kaoru Imai, Akifumi Hagi, Frederick H Neill, Robert L Atmar, B V Venkataram Prasad, Mary K Estes

Faculty, Staff and Students Publications

Human norovirus (HuNoV) is the leading cause of epidemic and sporadic acute gastroenteritis worldwide. HuNoV transmission occurs predominantly by direct person-to-person contact, and its health burden is associated with poor hand hygiene and a lack of effective antiseptics and disinfectants. Specific therapies and methods to prevent and control HuNoV spread previously were difficult to evaluate because of the lack of a cell culture system to propagate infectious virus. This barrier has been overcome with the successful cultivation of HuNoV in nontransformed human intestinal enteroids (HIEs). Here, we report using the HIE cultivation system to evaluate the virucidal efficacy of an …

The Chromosome-Level Rambutan Genome Reveals A Significant Role Of Segmental Duplication In The Expansion Of Resistance Genes, Jinfang Zheng1, Lyndel W. Meinhardt, Ricardo Goenaga, Tracie Matsumoto, Dapeng Zhang, Yanbin Yin

Food for Health: Publications

Rambutan (Nephelium lappaceum var. lappaceum), a tropical fruit tree native to southeastern Asia, belongs to the family Sapindaceae. Rambutan is a popular table fruit and is also processed into preserves, juices, wines, and sorbets [1]. At present, only three Sapindaceae genomes are publicly available: Xanthoceras sorbifolium [2], Dimocarpus longan (longan) [3], and Acer yangbiense [4]. During the process of submitting this manuscript, the genome paper for the rambutan cultivar Baoyan7 became available online, but its genome sequence has not yet been released [5].

Investigating Alternative Induction Of The S. Aureus 80a Prophage, Jody Caretti

Student Scholar Showcase

Widespread antibiotic resistance has quickly become one of the most concerning crises affecting modern medicine, especially in cases of Staphylococcal infections, which have become resistant to all ��-lactam antibiotics. As a result, research into alternative forms of treatment for bacterial infections is a top priority. Bacteriophage therapy is a popular candidate for replacing antibiotics, due to the way the viruses interact with the bacteria. The 80�� prophage integrates its DNA into Staphylococcus aureus strain 10616 via the lysogenic cycle, and replicates with the bacterial cell. When stressed, the bacteria stop replicating and the prophage stimulates the lytic cycle, activating transcription …