Single-Base Resolution Mapping of 5-Hydroxymethylcytosine Modifications in Hippocampus of Alzheimer\u27s Disease Subjects

Epigenetic modifications to cytosine have been shown to regulate transcription in cancer, embryonic development, and recently neurodegeneration. While cytosine methylation studies are now common in neurodegenerative research, hydroxymethylation studies are rare, particularly genome-wide mapping studies. As an initial study to analyze 5-hydroxymethylcytosine (5-hmC) in the Alzheimer’s disease (AD) genome, reduced representation hydroxymethylation profiling (RRHP) was used to analyze more than 2 million sites of possible modification in hippocampal DNA of sporadic AD and normal control subjects. Genes with differentially hydroxymethylated regions were filtered based on previously published microarray data for altered gene expression in hippocampal DNA of AD subjects. Our data show significant pathways for altered levels of 5-hmC in the hippocampus of AD subjects compared to age-matched normal controls involved in signaling, energy metabolism, cell function, gene expression, protein degradation, and cell structure and stabilization. Overall, our data suggest a possible role for the dysregulation of epigenetic modifications to cytosine in late stage AD

MR Imaging Radiomics Signatures for Predicting the Risk of Breast Cancer Recurrence as Given by Research Versions of MammaPrint, Oncotype DX, and PAM50 Gene Assays

To investigate relationships between computer-extracted breast magnetic resonance (MR) imaging phenotypes with multigene assays of MammaPrint, Oncotype DX, and PAM50 to assess the role of radiomics in evaluating the risk of breast cancer recurrence

Crystal Structures of Native and Inactivated cis-3-Chloroacrylic Acid Dehalogenase. Structural Basis for Substrate Specificity and Inactivation by (R)-Oxirane-2-Carboxylate

The bacterial degradation pathways for the nematocide 1,3-dichloropropene rely on hydrolytic dehalogenation reactions catalyzed by cis- and trans-3-chloroacrylic acid dehalogenases (cis-CaaD and CaaD, respectively). X-ray crystal structures of native cis-CaaD and cis-CaaD inactivated by (R)-oxirane-2-carboxylate were elucidated. They locate four known catalytic residues (Pro-1, Arg-70, Arg-73, and Glu-114) and two previously unknown, potential catalytic residues (His-28 and Tyr-103'). The Y103F and H28A mutants of these latter two residues displayed reductions in cis-CaaD activity confirming their importance in catalysis. The structure of the inactivated enzyme shows covalent modification of the Pro-1 nitrogen atom by (R)-2-hydroxypropanoate at the C3 position. The interactions in the complex implicate Arg-70 or a water molecule bound to Arg-70 as the proton donor for the epoxide ring-opening reaction and Arg-73 and His-28 as primary binding contacts for the carboxylate group. This proposed binding mode places the (R)-enantiomer, but not the (S)-enantiomer, in position to covalently modify Pro-1. The absence of His-28 (or an equivalent) in CaaD could account for the fact that CaaD is not inactivated by either enantiomer. The cis-CaaD structures support a mechanism in which Glu-114 and Tyr-103' activate a water molecule for addition to C3 of the substrate and His-28, Arg-70, and Arg-73 interact with the C1 carboxylate group to assist in substrate binding and polarization. Pro-1 provides a proton at C2. The involvement of His-28 and Tyr-103' distinguishes the cis-CaaD mechanism from the otherwise parallel CaaD mechanism. The two mechanisms probably evolved independently as the result of an early gene duplication of a common ancestor

The Grizzly, November 21, 1980

Dean of Students\u27 Office Releases Vandalism Figures • Maintenance Working To Conserve Energy • Weight Room Relocated In Helfferich • College Union Attempts World\u27s Largest Molecule • Ursinus News In Brief: Espadas to speak today in Illinois; Maintenance planting new trees; Placement interviews coming soon • Rassias Method Explored for Languages • Journalism To Be Added To Curriculum • Medical Ethics Course Offered • Phil. & Rel. Dept. Lecture On Judaism • College To Host 43rd Messiah Performance • Foghat and Outlaws Perform for \u27Serious Rockers\u27 • Forum On Radiation Draws Mixed Views • Art Exhibit On Display In Wismer • Open House Planned By Astronomy Club • A Look At This Year\u27s Basketball Season • Cross Country To Compete In Nationals This Weekend • Gridders Lose Early Lead to Tie Gettysburghttps://digitalcommons.ursinus.edu/grizzlynews/1048/thumbnail.jp

The Grizzly, September 26, 1980

Equipment Stolen From New Ritter Center • Conversion Eases Skyrocketing Utility Costs • Dean\u27s Office Discloses Frat GPAs • New Windows for NMD • New Spanish Lecturers Interviewed • IF, USGA to Sponsor Fall Picnic • Anderson Addresses College Crowd At Phila. Rally • College Invaded By World Of Technology • Draft Registration Closely Examined • Campus Grounds Receive Face Lift • Hamilton Presents Astronomy Discoveries • Try-outs for Trial by Jury • Weekends at Ursinus • Harriers Place 2nd At Lafayette Invitational • Grizzly Football Handled By W. Maryland • Sports Profile: Craig Walck • Field Hockey Finishes Week Undefeated • Strong Hitting By Bear V-Ball Outdoes Moravian • Offense Sputters As Bears Lose • Kreiger Powers Heathenshttps://digitalcommons.ursinus.edu/grizzlynews/1041/thumbnail.jp

Microbes in beach sands : integrating environment, ecology and public health

Author Posting. © The Author(s), 2014. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Reviews in Environmental Science and Bio/Technology 13 (2014): 329-368, doi:10.1007/s11157-014-9340-8.Beach sand is a habitat that supports many microbes, including viruses, bacteria, fungi and protozoa (micropsammon). The apparently inhospitable conditions of beach sand environments belie the thriving communities found there. Physical factors, such as water availability and protection from insolation; biological factors, such as competition, predation, and biofilm formation; and nutrient availability all contribute to the characteristics of the micropsammon. Sand microbial communities include autochthonous species/phylotypes indigenous to the environment. Allochthonous microbes, including fecal indicator bacteria (FIB) and waterborne pathogens, are deposited via waves, runoff, air, or animals. The fate of these microbes ranges from death, to transient persistence and/or replication, to establishment of thriving populations (naturalization) and integration in the autochthonous community. Transport of the micropsammon within the habitat occurs both horizontally across the beach, and vertically from the sand surface and ground water table, as well as at various scales including interstitial flow within sand pores, sediment transport for particle-associated microbes, and the large-scale processes of wave action and terrestrial runoff. The concept of beach sand as a microbial habitat and reservoir of FIB and pathogens has begun to influence our thinking about human health effects associated with sand exposure and recreational water use. A variety of pathogens have been reported from beach sands, and recent epidemiology studies have found some evidence of health risks associated with sand exposure. Persistent or replicating populations of FIB and enteric pathogens have consequences for watershed/beach management strategies and regulatory standards for safe beaches. This review summarizes our understanding of the community structure, ecology, fate, transport, and public health implications of microbes in beach sand. It concludes with recommendations for future work in this vastly under-studied area.2015-05-0

The Grizzly, October 10, 1980

Alternative Housing Investigated • Unchanged since 1960: Activity Fee Increase Likely • Freshman Class Select Officers • Work Stalled On Campus Beautification • Bermans Give Sculpture To College • Ursinus News In Brief: Student chemistry group honored; Study skills workshop to be repeated; College appoints pol sci lecturer • Off-Campus Houses Rewired • Fast Method Discovered for Wismer • African Politics Subject of Oct. 15 Forum • IF Council, USGA Host Fall Picnic • Inactive Alarm System Questioned • Steranko Plays To Sparse Crowd • The Art of Procrastination • Toga! Toga! Toga! • New Ritter Center Dedicated • How To Get To Philly Without A Car • Guide To Ursinus Vocabulary • Science Fiction Books Discussion Offered • Lantern Needs Help • CLC Reveals Findings From Survey • Homecoming Candidates • Three Intramural Teams Clinch Playoff Spot • Booters Take Two • Hockey\u27s Unbeaten Streak Broken • X-Country Places 2nd At Mansfieldhttps://digitalcommons.ursinus.edu/grizzlynews/1043/thumbnail.jp

The Grizzly, October 17, 1980

Clouser Organizes Medical Advisory Committee • Union Rules Out Greaseband This Year • Freshman Class Appointments Available • Education Department Optimistic About Jobs • New Profs Appointed In German, History Depts. • Parents\u27 Day Brings Campus Enthusiasm • Staiger Named for State Committee • College Offers Numerous Special Programs • Coffeehouse Of \u27Distant Admiration\u27 • Radio WRUC Making Slow Return • Forum Presents Tyler and Althea • Parents\u27 Day Sees Gym Dedication • SAC Approves Two New Clubs • \u27Gong Show\u27 Provides Friday Night Fun • College Bowl Season Officially Opens • Heathens Take Intramural Title • Booters Kick Del Valley • Women\u27s Volleyball Faces Tough Schedule • Football Finds Season\u27s First W • Hockey Raises Record To 6-1-3https://digitalcommons.ursinus.edu/grizzlynews/1044/thumbnail.jp

Elucidating the path to Plasmodium prolyl-tRNA synthetase inhibitors that overcome halofuginone resistance

© The Author(s) 2022 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.The development of next-generation antimalarials that are efficacious against the human liver and asexual blood stages is recognized as one of the world's most pressing public health challenges. In recent years, aminoacyl-tRNA synthetases, including prolyl-tRNA synthetase, have emerged as attractive targets for malaria chemotherapy. We describe the development of a single-step biochemical assay for Plasmodium and human prolyl-tRNA synthetases that overcomes critical limitations of existing technologies and enables quantitative inhibitor profiling with high sensitivity and flexibility. Supported by this assay platform and co-crystal structures of representative inhibitor-target complexes, we develop a set of high-affinity prolyl-tRNA synthetase inhibitors, including previously elusive aminoacyl-tRNA synthetase triple-site ligands that simultaneously engage all three substrate-binding pockets. Several compounds exhibit potent dual-stage activity against Plasmodium parasites and display good cellular host selectivity. Our data inform the inhibitor requirements to overcome existing resistance mechanisms and establish a path for rational development of prolyl-tRNA synthetase-targeted anti-malarial therapies.This work was supported by NIH R01AI143723 (R.M. and D.F.W.), NIH R01AI152533 (M.R.L. and E.A.W.), 5F31AI129412 (L.F.), and the Bill & Melinda Gates Foundation (OPP1054480, E.A.W. and D.F.W.), LEAN program of the Leducq Foundation (U.O.), Arthritis Research UK 20522 (U.O.), Cancer Research UK A23900 (U.O.). N.C.P. was supported by a National Science Foundation Graduate Research Fellowship (DGE1745303). M.R.L. was supported in part by a Ruth L. Kirschstein Institutional National Research Award from the National Institute for General Medical Sciences (T32 GM008666). This publication includes data generated at the University of California, San Diego IGM Genomics Center utilizing an Illumina NovaSeq 6000 that was purchased with funding from a National Institutes of Health SIG grant (#S10 OD026929).info:eu-repo/semantics/publishedVersio