Live imaging of SARS-CoV-2 infection in mice reveals neutralizing antibodies require Fc function for optimal efficacy

Neutralizing antibodies (NAbs) are effective in treating COVID-19 but the mechanism of immune protection is not fully understood. Here, we applied live bioluminescence imaging (BLI) to monitor the real-time effects of NAb treatment in prophylaxis and therapy of K18-hACE2 mice intranasally infected with SARS-CoV-2-nanoluciferase. We visualized sequential spread of virus from the nasal cavity to the lungs followed by systemic spread to various organs including the brain, culminating in death. Highly potent NAbs from a COVID-19 convalescent subject prevented, and also effectively resolved, established infection when administered within three days of infection. In addition to direct neutralization, in vivo efficacy required Fc effector functions of NAbs, with contributions from monocytes, neutrophils and natural killer cells, to dampen inflammatory responses and limit immunopathology. Thus, our study highlights the requirement of both Fab and Fc effector functions for an optimal in vivo efficacy afforded by NAbs against SARS-CoV-2

Aggression, anxiety and vocalizations in animals: GABA A and 5-HT anxiolytics

A continuing challenge for preclinical research on anxiolytic drugs is to capture the affective dimension that characterizes anxiety and aggression, either in their adaptive forms or when they become of clinical concern. Experimental protocols for the preclinical study of anxiolytic drugs typically involve the suppression of conditioned or unconditioned social and exploratory behavior (e.g., punished drinking or social interactions) and demonstrate the reversal of this behavioral suppression by drugs acting on the benzodiazepine-GABA A complex. Less frequently, aversive events engender increases in conditioned or unconditioned behavior that are reversed by anxiolytic drugs (e.g., fear-potentiated startle). More recently, putative anxiolytics which target 5-HT receptor subtypes produced effects in these traditional protocols that often are not systematic and robust. We propose ethological studies of vocal expressions in rodents and primates during social confrontations, separation from social companions, or exposure to aversive environmental events as promising sources of information on the affective features of behavior. This approach focusses on vocal and other display behavior with clear functional validity and homology. Drugs with anxiolytic effects that act on the benzodiazepine-GABA A receptor complex and on 5-HT 1A receptors systematically and potently alter specific vocalizations in rodents and primates in a pharmacologically reversible manner; the specificity of these effects on vocalizations is evident due to the effectiveness of low doses that do not compromise other physiological and behavioral processes. Antagonists at the benzodiazepine receptor reverse the effects of full agonists on vocalizations, particularly when these occur in threatening, startling and distressing contexts. With the development of antagonists at 5-HT receptor subtypes, it can be anticipated that similar receptor-specificity can be established for the effects of 5-HT anxiolytics.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46351/1/213_2005_Article_BF02245590.pd

HISTORICAL, SOCIAL AND AESTHETICAL DISCOURSE IN THE ARCHITECTURE OF VILNIUS FOUNTAINS / ISTORINIS, SOCIALINIS IR ESTETINIS DISKURSAS VILNIAUS FONTANŲ ARCHITEKTŪROJE

This article attempts to review connections between Vilnius city culture and water, as an architectural mean. It aims to determine social and aesthetical aspects of water in development of Vilnius architecture in the context of cultural flux and changing urbanistic concepts. The main research methods are the interpretation of texts, historical reflection and analysis of cartographic material. In Vilnius architecture, water reflects functional principles and artistic conceptions of various historical periods. The usage of water as an aesthetic means was commenced in Renaissance Vilnius sculpture fountains. During the Soviet period, regardless of the heritage and historical traditions, geometrically developed city structure destroyed individual character and aesthetic charm. By absolutizing of geometric forms, modern urbanists deprived the city of life and individuality. Aesthetic value of water had been annulled and fountains were designed solely on the basis of technical and ideological considerations. In the discourse of modern Lithuanian urbanism, return to the aesthetic dimension of water is observed along with innovative management schemes and technologies, ecology and art. In the conclusion it is revealed, that throughout history, it has formed only weak link between water and cultural identity. This resulted, that water, as architectural tool for social influence, was used more by external forces, rather than for internal Lithuanian cultural purposes. In the meantime, the discourse is forming, which could result in future developments of the issue. Santrauka  Straipsnyje bandoma apžvelgti Vilniaus miesto kultūros ir vandens, kaip architektūrinės priemonės sąsajas. Iškeliamas tikslas nustatyti vandens socialinius ir estetinius aspektus Vilniaus miesto architektūros raidoje, besikeičiant urbanistikos koncepcijoms ir kintant kultūrinėms vertybėms. Pagrindiniai tyrimo metodai – tekstų interpretacija, istorinė refleksija bei kartografinės medžiagos analizė. Vanduo Vilniaus architektūroje atspindi įvairių laikotarpių funkcionalumo principus ir menines koncepcijas. Renesanso laikotarpiu Vilniaus skulptūriniuose fontanuose vandenį pradėta naudoti kaip estetinę priemonę. Sovietiniu periodu, neatsižvelgiant į praeities paveldą ir istorines tradicijas, geometriškai plėtojama miesto struktūra naikino individualų charakterį ir estetinį žavesį. Tuometinė urbanistika suabsoliutino geometrines formas, atimdama miestams gyvybę ir žmonių bendrumą. Vandens estetinė reikšmė buvo anuliuota, fontanai projektuojami remiantis techniniais bei ideologiniais motyvais, tačiau neapsieita ir be užslėptos, metaforinės prasmės. Šiuolaikiniame lietuviškame urbanistikos diskurse grįžtama prie estetinės dimensijos, prie vandens valdymo schemų su naujomis technologijomis, ekologija ir menu. Išvadose atskleidžiama, kad istorijos eigoje nusistovėjo silpnas ryšys tarp vandens ir kultūrinio tapatumo, todėl ši architektūrinė priemonė, kaip socialinis įtaigos įrankis, sąmoningai taikyta veikiau išorinių jėgų, nei vidinėms lietuviškos kultūros reikmėms. Nepaisant to, pastaruoju metu formuojasi diskursas, kuris gali turėti potencialo ateities pokyčiams. Reikšminiai žodžiai: vanduo, architektūra, estetika, Vilniaus fontanai, miesto kultūra, urbanizacija