Pharmacological modulators of epithelial immunity uncovered by synthetic genetic tracing of SARS-CoV-2 infection responses

Epithelial immune responses govern tissue homeostasis and offer drug targets against maladaptation. Here, we report a framework to generate drug discovery–ready reporters of cellular responses to viral infection. We reverse-engineered epithelial cell responses to SARS-CoV-2, the viral agent fueling the ongoing COVID-19 pandemic, and designed synthetic transcriptional reporters whose molecular logic comprises interferon-α/β/γ and NF-κB pathways. Such regulatory potential reflected single-cell data from experimental models to severe COVID-19 patient epithelial cells infected by SARS-CoV-2. SARS-CoV-2, type I interferons, and RIG-I drive reporter activation. Live-cell image–based phenotypic drug screens identified JAK inhibitors and DNA damage inducers as antagonistic modulators of epithelial cell response to interferons, RIG-I stimulation, and SARS-CoV-2. Synergistic or antagonistic modulation of the reporter by drugs underscored their mechanism of action and convergence on endogenous transcriptional programs. Our study describes a tool for dissecting antiviral responses to infection and sterile cues and rapidly discovering rational drug combinations for emerging viruses of concern

Cloning of somatolactin alpha, beta forms and the somatolactin receptor in Atlantic salmon: Seasonal expression profile in pituitary and ovary of maturing female broodstock

<p>Abstract</p> <p>Background</p> <p>Somatolactin (Sl) is a fish specific adenohypophyseal peptide hormone related to growth hormone (Gh). Some species, including salmonids, possess two forms: Sl alpha and Sl beta. The somatolactin receptor (slr) is closely related to the growth hormone receptor (ghr). Sl has been ascribed many physiological functions, including a role in sexual maturation. In order to clarify the role of Sl in the sexual maturation of female Atlantic salmon (Salmo salar), the full length cDNAs of slr, Sl alpha and Sl beta were cloned and their expression was studied throughout a seasonal reproductive cycle using real-time quantitative PCR (RTqPCR).</p> <p>Methods</p> <p>Atlantic salmon Sl alpha, Sl beta and slr cDNAs were cloned using a PCR approach. Gene expression of Sl alpha, SL beta and slr was studied using RTqPCR over a 17 month period encompassing pre-vitellogenesis, vitellogenesis, ovulation and post ovulation in salmon females. Histological examination of ovarian samples allowed for the classification according to the degree of follicle maturation into oil drop, primary, secondary or tertiary yolk stage.</p> <p>Results</p> <p>The mature peptide sequences of Sl alpha, Sl beta and slr are highly similar to previously cloned salmonid forms and contained the typical motifs. Phylogenetic analysis of Atlantic salmon Sl alpha and Sl beta shows that these peptides group into the two Sl clades present in some fish species. The Atlantic salmon slr grouped with salmonid slr amongst so-called type I ghr. An increase in pituitary Sl alpha and Sl beta transcripts before and during spawning, with a decrease post-ovulation, and a constant expression level of ovarian slr were observed. There was also a transient increase in Sl alpha and Sl beta in May prior to transfer from seawater to fresh water and ensuing fasting.</p> <p>Conclusion</p> <p>The up-regulation of Sl alpha and Sl beta during vitellogenesis and spawning, with a subsequent decrease post-ovulation, supports a role for Sl during gonadal growth and spawning. Sl could also be involved in calcium/phosphate mobilization associated with vitellogenesis or have a role in energy homeostasis associated with lipolysis during fasting. The up-regulation of both Sl alpha and Sl beta prior to fasting and freshwater transfer, suggests a role for Sl linked to reproduction that may be independent of the maturation induced fasting.</p

Rand McNally Popular map of South America

Mapa político de América del Sur, contiene información político administrativa dividida a color, incluye lista de las principales ciudades con coordenadas para localizar en el mapa y cifras poblacionales por países. Contiene cartela de las Islas Galápagos Hace parte de: “Rand McNally World Atla” publicado por Rand McNally , una imprenta creada en 1868 por William Rand y Andrew McNally, se caracterizaron por la publicación de mapas y atlas educativos así como rutas de carreteras, fueron los primeros editores en adoptar un sistema de autopistas numeradas con señales de transito reales. Longitud con respecto al meridiano de Greenwich. Trazado de la línea del Ecuador y del Trópico de Capricornio. Escala expresada en millas y kilómetros

Rand McNally Popular map of Mexico

Rand McNally fue una imprenta creada en 1868 por William Rand y Andrew McNally, se caracterizaron por la publicación de mapas y atlas educativos así como rutas de carreteras, fueron los primeros editores en adoptar un sistema de autopistas numeradas con señales de transito reales. Este mapa político de México, trazado publicado por dicha imprenta incluye lista de principales ciudades con coordenadas de localización en el mapa y cifras de cantidad poblacional. Contiene Cartela de México D.F. con sus colonias. Hace parte de: “Rand McNally World Atlas” Longitud con respecto al meridiano de Greenwich Trazado del Trópico de Cáncer. Escala expresada en millas y kilómetros

Indonesia 1958

Map in Indonesian and English.Color;1:1,4000,00

The Rand-McNally indexed county and township pocket map and shippers guide of Florida showing all railroads, cities, towns, villages, post offices, lakes, rivers, etc.

Shows in detail the entire railroad network in red, coded by number to list.Scale 1:1,203,840.Title from index.LC Railroad maps, 197Description derived from published bibliography.Inset: Map showing parts of Lake, Orange and Volusa counties. 14 x 22 cm.Accompanied by index

Classification territories, certain freight association territories, and certain common points.

Map shows boundaries for freight classification associations and major railroad "termini" for northern Mexico, southern Canada, and the continental United States; state boundaries, major cities, and railroads lines. Relief shown by hachures. Scale not given

Washington.

Explanation and supporting information related to map that shows early nineteenth century Washington counties, township grid, Native American reservations, railroads, national parks, and notable physical features

Washington.

Map shows railroads, counties, cities, towns, Native American reservations, and notable physical features. Includes area statistics, index to counties and chief cities in upper and lower margins for each map. Inset: "Outline map of Washington showing city limits, parks, and boulevards." Scale [ca. 1:2,154,240] and [ca. 1:2,027,520]