Pseudomonas aeruginosa Expresses a Functional Human Natriuretic Peptide Receptor Ortholog: Involvement in Biofilm Formation

This is the final version of the article. Available from the publisher via the DOI in this record.Considerable evidence exists that bacteria detect eukaryotic communication molecules and modify their virulence accordingly. In previous studies, it has been demonstrated that the increasingly antibiotic-resistant pathogen Pseudomonas aeruginosa can detect the human hormones brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) at micromolar concentrations. In response, the bacterium modifies its behavior to adapt to the host physiology, increasing its overall virulence. The possibility of identifying the bacterial sensor for these hormones and interfering with this sensing mechanism offers an exciting opportunity to directly affect the infection process. Here, we show that BNP and CNP strongly decrease P. aeruginosa biofilm formation. Isatin, an antagonist of human natriuretic peptide receptors (NPR), prevents this effect. Furthermore, the human NPR-C receptor agonist cANF(4-23) mimics the effects of natriuretic peptides on P. aeruginosa, while sANP, the NPR-A receptor agonist, appears to be weakly active. We show in silico that NPR-C, a preferential CNP receptor, and the P. aeruginosa protein AmiC have similar three-dimensional (3D) structures and that both CNP and isatin bind to AmiC. We demonstrate that CNP acts as an AmiC agonist, enhancing the expression of the ami operon in P. aeruginosa. Binding of CNP and NPR-C agonists to AmiC was confirmed by microscale thermophoresis. Finally, using an amiC mutant strain, we demonstrated that AmiC is essential for CNP effects on biofilm formation. In conclusion, the AmiC bacterial sensor possesses structural and pharmacological profiles similar to those of the human NPR-C receptor and appears to be a bacterial receptor for human hormones that enables P. aeruginosa to modulate biofilm expression. IMPORTANCE: The bacterium Pseudomonas aeruginosa is a highly dangerous opportunist pathogen for immunocompromised hosts, especially cystic fibrosis patients. The sites of P. aeruginosa infection are varied, with predominance in the human lung, in which bacteria are in contact with host molecular messengers such as hormones. The C-type natriuretic peptide (CNP), a hormone produced by lung cells, has been described as a bacterial virulence enhancer. In this study, we showed that the CNP hormone counteracts P. aeruginosa biofilm formation and we identified the bacterial protein AmiC as the sensor involved in the CNP effects. We showed that AmiC could bind specifically CNP. These results show for the first time that a human hormone could be sensed by bacteria through a specific protein, which is an ortholog of the human receptor NPR-C. The bacterium would be able to modify its lifestyle by favoring virulence factor production while reducing biofilm formation.We thank Magalie Barreau and Olivier Maillot for technical assistance. We thank Christine Farmer for linguistic insight for the manuscript. T. Rosay is a recipient of a doctoral fellowship from the French Ministry of Research (MRE). This work was supported by grants from the Communauté d’Agglomération d’Evreux, the Conseil Général de l’Eure, European Union (FEDER no. 31970), the French Association “Vaincre la Mucoviscidose” and the InterReg IVA PeReNE project

1938: Abilene Christian College Bible Lectures - Full Text

Delivered in the Auditorium of Abilene Christian College, February, 1938 Abilene, Texas. Published October, 1939 PRICE, $1.00 FIRM FOUNDATION PUBLISHING HOUSE Austin, Texas

Selected data fron continental scientific drilling core holes VC-1 and VC-2a, Valles Caldera, New Mexico

This report presents geochemical and isotopic data on rocks and water and wellbore geophysical data from the Continental Scientific Drilling Program core holes VC-1 and VC-2a, Valles Caldera, New Mexico. These core holes were drilled as a portion of a broader program that seeks to answer fundamental questions about magma, water/rock interactions, ore deposits, and volcanology. The data in this report will assist the interpretation of the hydrothermal system in the Jemez Mountains and will stimulate further research in magmatic processes, hydrothermal alteration, ore deposits, hydrology, structural geology, and hydrothermal solution chemistry. 37 refs., 36 figs., 28 tabs

1958: Abilene Christian College Bible Lectures - Full Text

“GOD” Being the Abilene Christian College Annual Bible Lectures 1958 Price: $3.00 Published by FIRM FOUNDATION PUBLISHING HOUSE Box 77 Austin, Texa

Two decades of dynamic change and progressive destabilization on the Thwaites Eastern Ice Shelf

The Thwaites Eastern Ice Shelf (TEIS) buttresses the eastern grounded portion of Thwaites Glacier through contact with a pinning point at its seaward limit. Loss of this ice shelf will promote further acceleration of Thwaites Glacier. Understanding the dynamic controls and structural integrity of the TEIS is therefore important to estimating Thwaites' future sea-level contribution. We present a &sim;&thinsp;20-year record of change on the TEIS that reveals the dynamic controls governing the ice shelf's past behaviour and ongoing evolution. We derived ice velocities from MODIS and Sentinel-1 image data using feature tracking and speckle tracking, respectively, and we combined these records with ITS_LIVE and GOLIVE velocity products from Landsat-7 and Landsat-8. In addition, we estimated surface lowering and basal melt rates using the Reference Elevation Model of Antarctica (REMA) DEM in comparison to ICESat and ICESat-2 altimetry. Early in the record, TEIS flow dynamics were strongly controlled by the neighbouring Thwaites Western Ice Tongue (TWIT). Flow patterns on the TEIS changed following the disintegration of the TWIT around 2008, with a new divergence in ice flow developing around the pinning point at its seaward limit. Simultaneously, the TEIS developed new rifting that extends from the shear zone upstream of the ice rise and increased strain concentration within this shear zone. As these horizontal changes occurred, sustained thinning driven by basal melt reduced ice thickness, particularly near the grounding line and in the shear zone area upstream of the pinning point. This evidence of weakening at a rapid pace suggests that the TEIS is likely to fully destabilize in the next few decades, leading to further acceleration of Thwaites Glacier. &nbsp;</p

1956: Abilene Christian College Bible Lectures - Full Text

Golden Anniversary Edition featuring the theme THEY SHALL ALL BE TAUGHT OF GOD Price: $3.50 FIRM FOUNDATION PUBLISHING HOUSE Box 77 Austin, Texa

1960: Abilene Christian College Lectures - Full Text

Table of Contents: Theme Speeches: Christian Faith in the Modern World Basis of Faith - Leonard Mullens - 9 Authority in Christianity - John T. Smithson, Jr. - 27 Origin and Preservation of the Bible - Neil R. Lightfoot - 44 Alleged Discrepancies of the Bible - David H. Bobo - 62 The Unity of the Bible - Jack Meyer - 91 Faith and Reason - Joe Sanders - 115 The Reasonableness of Supernaturalism - Virgil Trout - 126 The Present Statue of the Doctrine of Organic Evolution - J.D. Thomas - 146 The Nature of Man - Roy F. Osborne, Jr. - 181 Modern Challenges to Christian Morals - Carl Spain - 199 The Christ, Whose Son is He? - Gordon Teel - 232 Special Speeches Teaching the Word of God in Korea - L. Haskell Chessfire - 255 The Influence of Christian Education - Judge Jack Pope - 276 Mission Opportunities in the Far East - Harry Robert Fox - 288 Mission Work in Austria - Robert Skelton - 303 Report from Switzerland - Heinrich Blum - 313 The Work in Nigeria - Rees Byrant - 320 The Training of Evangelists in Foreign Fields - Reiner Kallus - 331 Christian Scholarships - Everett Ferguson - 340 Evangelizing the World - A.R. Holton - 349 Panel Discussions The Significance of the Dead Sea Scrolls The Scrolls and the Text of the Bible - Paul Rotenberry - 357 The Relation between the Religion of the Essenes and that of Early Christians - Jay Smith - 366 Biblical Interpretation Expediency and Pattern Authority - J.W. Roberts - 381 Examples in Pattern Authority - Thomas B. Warren - 392 Mental Health and Sin The Present State of Mental Health Knowledge - Donald R. Sime - 409 The Relationship of Mental Health Problems to Sin - Paul Easley - 421 The Teenager The Problems of Youth - Mack Wayne Craig - 432 Influences for Good - Wyatt Sawyer - 443 The Benefits of Abilene Christian College To the Church - Hulen Jackson - 451 To The Home - Robert S. Bell - 459 \u27To the Community - Louie Welch - 465 Expenses At Abilene Christian College - James C. Kerr - 469 The Graduate School at Abilene Christian College What I Am Getting Now in the ACC Graduate Program - Harold Vanderpool - 475 How the ACC Graduate Program Has Stood Up - Everett Ferguson - 481 What the ACC Graduate Program Ought To Be - Frank Pack - 486 The Importance to the Church of the ACC Graduate Program A.R. Holton - 490 Beware: Large File Size Uploaded by Jackson Hage

Capsid-like particles decorated with the SARS-CoV-2 receptor-binding domain elicit strong virus neutralization activity

The rapid development of a SARS-CoV-2 vaccine is a global priority. Here, we develop two capsid-like particle (CLP)-based vaccines displaying the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. RBD antigens are displayed on AP205 CLPs through a split-protein Tag/Catcher, ensuring unidirectional and high-density display of RBD. Both soluble recombinant RBD and RBD displayed on CLPs bind the ACE2 receptor with nanomolar affinity. Mice are vaccinated with soluble RBD or CLP-displayed RBD, formulated in Squalene-Water-Emulsion. The RBD-CLP vaccines induce higher levels of serum anti-spike antibodies than the soluble RBD vaccines. Remarkably, one injection with our lead RBD-CLP vaccine in mice elicits virus neutralization antibody titers comparable to those found in patients that had recovered from COVID-19. Following booster vaccinations, the virus neutralization titers exceed those measured after natural infection, at serum dilutions above 1:10,000. Thus, the RBD-CLP vaccine is a highly promising candidate for preventing COVID-19.Molecular basis of virus replication, viral pathogenesis and antiviral strategie

Mechanism of KMT5B haploinsufficiency in neurodevelopment in humans and mice.

Pathogenic variants in KMT5B, a lysine methyltransferase, are associated with global developmental delay, macrocephaly, autism, and congenital anomalies (OMIM# 617788). Given the relatively recent discovery of this disorder, it has not been fully characterized. Deep phenotyping of the largest (n = 43) patient cohort to date identified that hypotonia and congenital heart defects are prominent features that were previously not associated with this syndrome. Both missense variants and putative loss-of-function variants resulted in slow growth in patient-derived cell lines. KMT5B homozygous knockout mice were smaller in size than their wild-type littermates but did not have significantly smaller brains, suggesting relative macrocephaly, also noted as a prominent clinical feature. RNA sequencing of patient lymphoblasts and Kmt5b haploinsufficient mouse brains identified differentially expressed pathways associated with nervous system development and function including axon guidance signaling. Overall, we identified additional pathogenic variants and clinical features in KMT5B-related neurodevelopmental disorder and provide insights into the molecular mechanisms of the disorder using multiple model systems

In vitro synthesis of large peptide molecules using glucosylated single-stranded bacteriophage T4D DNA template.

Denatured Bacteriophage T4D DNA is able to stimulate aminoacid incorporation into TCA-precipitable material in an in vitro protein synthesis system according to base DNA sequences. Newly synthesized polypeptides remain associated with ribosomes and have a molecular weight in range of 15,000 to 45,000 Daltons