Social transmission of leadership preference:knowledge of group membership and partisan media reporting moderates perceptions of leadership ability from facial cues to competence and dominance

While first impressions of dominance and competence can influence leadership preference, social transmission of leadership preference has received little attention. The capacity to transmit, store and compute information has increased greatly over recent history, and the new media environment may encourage partisanship (i.e. ‘echo chambers’), misinformation and rumour spreading to support political and social causes and be conducive both to emotive writing and emotional contagion, which may shape voting behaviour. In our pre-registered experiment, we examined whether implicit associations between facial cues to dominance and competence (intelligence) and leadership ability are strengthened by partisan media and knowledge that leaders support or oppose us on a socio-political issue of personal importance. Social information, in general, reduced well-established implicit associations between facial cues and leadership ability. However, as predicted, social knowledge of group membership reduced preferences for facial cues to high dominance and intelligence in out-group leaders. In the opposite-direction to our original prediction, this ‘in-group bias’ was greater under less partisan versus partisan media, with partisan writing eliciting greater state anxiety across the sample. Partisanship also altered the salience of women’s facial appearance (i.e., cues to high dominance and intelligence) in out-group versus in-group leaders. Independent of the media environment, men and women displayed an in-group bias toward facial cues of dominance in same-sex leaders. Our findings reveal effects of minimal social information (facial appearance, group membership, media reporting) on leadership judgements, which may have implications for patterns of voting or socio-political behaviour at the local or national level

Own attractiveness and perceived relationship quality shape sensitivity in women’s memory for other men on the attractiveness dimension

Although recent work suggests that opposite-sex facial attractiveness is less salient in memory when individuals are in a committed romantic relationship, romantic relationship quality can vary over time. In light of this, we tested whether activating concerns about romantic relationship quality strengthens memory for attractive faces. Partnered women were exposed briefly to faces manipulated in shape cues to attractiveness before either being asked to think about a moment of emotional closeness or distance in their current relationship. We measured sensitivity in memory for faces as the extent to which they recognized correct versions of studied faces over versions of the same person altered to look either more or less-attractive than their original (i.e. studied) version. Contrary to predictions, high relationship quality strengthened hit rate for faces regardless of the sex or attractiveness of the face. In general, women’s memories were more sensitive to attractiveness in women, but were biased toward attractiveness in male faces, both when responding to unfamiliar faces and versions of familiar faces that were more attractive than the original male identity from the learning phase. However, findings varied according to self-rated attractiveness and a psychometric measure of the quality of their current relationship. Attractive women were more sensitive to attractiveness in men, while their less-attractive peers had a stronger bias to remember women as more-attractive and men as less-attractive than their original image respectively. Women in better-quality romantic relationships had stronger positive biases toward, and false memories for, attractive men. Our findings suggest a sophisticated pattern of sensitivity and bias in women’s memory for facial cues to quality that varies systematically according to factors that may alter the costs of female mating competition (‘market demand’) and relationship maintenance

LAGEOS-type Satellites in Critical Supplementary Orbit Configuration and the Lense-Thirring Effect Detection

In this paper we analyze quantitatively the concept of LAGEOS--type satellites in critical supplementary orbit configuration (CSOC) which has proven capable of yielding various observables for many tests of General Relativity in the terrestrial gravitational field, with particular emphasis on the measurement of the Lense--Thirring effect.Comment: LaTex2e, 20 pages, 7 Tables, 6 Figures. Changes in Introduction, Conclusions, reference added, accepted for publication in Classical and Quantum Gravit

Glucagon like peptide-1 receptor agonists as neuroprotective agents for ischemic stroke: a systematic scoping review

Stroke mortality and morbidity is expected to rise. Despite considerable recent advances within acute ischemic stroke treatment, scope remains for development of widely applicable neuroprotective agents. Glucagon like peptide-1 receptor agonists (GLP-1RAs), originally licensed for the management of Type 2 Diabetes Mellitus, have demonstrated pre-clinical neuroprotective efficacy in a range of neurodegenerative conditions. This systematic scoping review reports the pre-clinical basis of GLP-1RAs as neuroprotective agents in acute ischemic stroke and their translation into clinical trials. We included 35 pre-clinical studies, 11 retrospective database studies, 7 cardiovascular outcome trials and 4 prospective clinical studies. Pre-clinical neuroprotection was demonstrated in normoglycemic models when administration was delayed by up to 24-hours following stroke induction. Outcomes included reduced infarct volume, apoptosis, oxidative stress and inflammation alongside increased neurogenesis, angiogenesis and cerebral blood flow. Improved neurological function and a trend towards increased survival were also reported. Cardiovascular outcomes trials reported a significant reduction in stroke incidence with semaglutide and dulaglutide. Retrospective database studies show a trend towards neuroprotection. Prospective interventional clinical trials are on-going, but initial indicators of safety and tolerability are favourable. Ultimately, we propose that repurposing GLP-1RAs is potentially advantageous but appropriately designed trials are needed to determine clinical efficacy and cost-effectiveness

A recombinant herpesviral vector containing a near-full-length SIVmac239 genome produces SIV particles and elicits immune responses to all nine SIV gene products

The properties of the human immunodeficiency virus (HIV) pose serious difficulties for the development of an effective prophylactic vaccine. Here we describe the construction and characterization of recombinant (r), replication-competent forms of rhesus monkey rhadinovirus (RRV), a gamma-2 herpesvirus, containing a near-full-length (nfl) genome of the simian immunodeficiency virus (SIV). A 306-nucleotide deletion in the pol gene rendered this nfl genome replication-incompetent as a consequence of deletion of the active site of the essential reverse transcriptase enzyme. Three variations were constructed to drive expression of the SIV proteins: one with SIV\u27s own promoter region, one with a cytomegalovirus (cmv) immediate-early promoter/enhancer region, and one with an RRV dual promoter (p26 plus PAN). Following infection of rhesus fibroblasts in culture with these rRRV vectors, synthesis of the early protein Nef and the late structural proteins Gag and Env could be demonstrated. Expression levels of the SIV proteins were highest with the rRRV-SIVcmv-nfl construct. Electron microscopic examination of rhesus fibroblasts infected with rRRV-SIVcmv-nfl revealed numerous budding and mature SIV particles and these infected cells released impressive levels of p27 Gag protein ( \u3e 150 ng/ml) into the cell-free supernatant. The released SIV particles were shown to be incompetent for replication. Monkeys inoculated with rRRV-SIVcmv-nfl became persistently infected, made readily-detectable antibodies against SIV, and developed T-cell responses against all nine SIV gene products. Thus, rRRV expressing a near-full-length SIV genome mimics live-attenuated strains of SIV in several important respects: the infection is persistent; \u3e 95% of the SIV proteome is naturally expressed; SIV particles are formed; and CD8+ T-cell responses are maintained indefinitely in an effector-differentiated state. Although the magnitude of anti-SIV immune responses in monkeys infected with rRRV-SIVcmv-nfl falls short of what is seen with live-attenuated SIV infection, further experimentation seems warranted

AIDS virus–specific CD8+ T lymphocytes against an immunodominant cryptic epitope select for viral escape

Cryptic major histocompatibility complex class I epitopes have been detected in several pathogens, but their importance in the immune response to AIDS viruses remains unknown. Here, we show that Mamu-B*17+ simian immunodeficiency virus (SIV)mac239-infected rhesus macaques that spontaneously controlled viral replication consistently made strong CD8+ T lymphocyte (CD8-TL) responses against a cryptic epitope, RHLAFKCLW (cRW9). Importantly, cRW9-specific CD8-TL selected for viral variation in vivo and effectively suppressed SIV replication in vitro, suggesting that they might play a key role in the SIV-specific response. The discovery of an immunodominant CD8-TL response in elite controller macaques against a cryptic epitope suggests that the AIDS virus–specific cellular immune response is likely far more complex than is generally assumed

Non-neutralizing Antibodies May Contribute to Suppression of SIVmac239 Viremia in Indian Rhesus Macaques

The antiviral properties of broadly neutralizing antibodies against HIV are well-documented but no vaccine is currently able to elicit protective titers of these responses in primates. While current vaccine modalities can readily induce non-neutralizing antibodies against simian immunodeficiency virus (SIV) and HIV, the ability of these responses to restrict lentivirus transmission and replication remains controversial. Here, we investigated the antiviral properties of non-neutralizing antibodies in a group of Indian rhesus macaques (RMs) that were vaccinated with vif, rev, tat, nef, and env, as part of a previous study conducted by our group. These animals manifested rapid and durable control of viral replication to below detection limits shortly after SIVmac239 infection. Although these animals had no serological neutralizing activity against SIVmac239 prior to infection, their pre-challenge titers of Env-binding antibodies correlated with control of viral replication. To assess the contribution of anti-Env humoral immune responses to virologic control in two of these animals, we transiently depleted their circulating antibodies via extracorporeal plasma immunoadsorption and inhibition of IgG recycling through antibody-mediated blockade of the neonatal Fc receptor. These procedures reduced Ig serum concentrations by up to 80% and temporarily induced SIVmac239 replication in these animals. Next, we transferred purified total Ig from the rapid controllers into six vaccinated RMs one day before intrarectal challenge with SIVmac239. Although recipients of the hyperimmune anti-SIV Ig fraction were not protected from infection, their peak and chronic phase viral loads were significantly lower than those in concurrent unvaccinated control animals. Together, our results suggest that non-neutralizing Abs may play a role in the suppression of SIVmac239 viremia

Nasal Host Response-Based Screening for Undiagnosed Respiratory Viruses: A Pathogen Surveillance and Detection Study

BACKGROUND: Symptomatic patients who test negative for common viruses are an important possible source of unrecognised or emerging pathogens, but metagenomic sequencing of all samples is inefficient because of the low likelihood of finding a pathogen in any given sample. We aimed to determine whether nasopharyngeal CXCL10 screening could be used as a strategy to enrich for samples containing undiagnosed viruses. METHODS: In this pathogen surveillance and detection study, we measured CXCL10 concentrations from nasopharyngeal swabs from patients in the Yale New Haven health-care system, which had been tested at the Yale New Haven Hospital Clinical Virology Laboratory (New Haven, CT, USA). Patients who tested negative for a panel of respiratory viruses using multiplex PCR during Jan 23-29, 2017, or March 3-14, 2020, were included. We performed host and pathogen RNA sequencing (RNA-Seq) and analysis for viral reads on samples with CXCL10 higher than 1 ng/mL or CXCL10 testing and quantitative RT-PCR (RT-qPCR) for SARS-CoV-2. We used RNA-Seq and cytokine profiling to compare the host response to infection in samples that were virus positive (rhinovirus, seasonal coronavirus CoV-NL63, or SARS-CoV-2) and virus negative (controls). FINDINGS: During Jan 23-29, 2017, 359 samples were tested for ten viruses on the multiplex PCR respiratory virus panel (RVP). 251 (70%) were RVP negative. 60 (24%) of 251 samples had CXCL10 higher than 150 pg/mL and were identified for further analysis. 28 (47%) of 60 CXCL10-high samples were positive for seasonal coronaviruses. 223 (89%) of 251 samples were PCR negative for 15 viruses and, of these, CXCL10-based screening identified 32 (13%) samples for further analysis. Of these 32 samples, eight (25%) with CXCL10 concentrations higher than 1 ng/mL and sufficient RNA were selected for RNA-Seq. Microbial RNA analysis showed the presence of influenza C virus in one sample and revealed RNA reads from bacterial pathobionts in four (50%) of eight samples. Between March 3 and March 14, 2020, 375 (59%) of 641 samples tested negative for 15 viruses on the RVP. 32 (9%) of 375 samples had CXCL10 concentrations ranging from 100 pg/mL to 1000 pg/mL and four of those were positive for SARS-CoV-2. CXCL10 elevation was statistically significant, and a distinguishing feature was found in 28 (8%) of 375 SARS-CoV-2-negative samples versus all four SARS-CoV-2-positive samples (p=4·4 × 10 INTERPRETATION: These results confirm CXCL10 as a robust nasopharyngeal biomarker of viral respiratory infection and support host response-based screening followed by metagenomic sequencing of CXCL10-high samples as a practical approach to incorporate clinical samples into pathogen discovery and surveillance efforts. FUNDING: National Institutes of Health, the Hartwell Foundation, the Gruber Foundation, Fast Grants for COVID-19 research from the Mercatus Center, and the Huffman Family Donor Advised Fund

Macaques vaccinated with live-attenuated SIV control replication of heterologous virus

An effective AIDS vaccine will need to protect against globally diverse isolates of HIV. To address this issue in macaques, we administered a live-attenuated simian immunodeficiency virus (SIV) vaccine and challenged with a highly pathogenic heterologous isolate. Vaccinees reduced viral replication by ∼2 logs between weeks 2–32 (P ≤ 0.049) postchallenge. Remarkably, vaccinees expressing MHC-I (MHC class I) alleles previously associated with viral control completely suppressed acute phase replication of the challenge virus, implicating CD8+ T cells in this control. Furthermore, transient depletion of peripheral CD8+ lymphocytes in four vaccinees during the chronic phase resulted in an increase in virus replication. In two of these animals, the recrudescent virus population contained only the vaccine strain and not the challenge virus. Alarmingly, however, we found evidence of recombinant viruses emerging in some of the vaccinated animals. This finding argues strongly against an attenuated virus vaccine as a solution to the AIDS epidemic. On a more positive note, our results suggest that MHC-I–restricted CD8+ T cells contribute to the protection induced by the live-attenuated SIV vaccine and demonstrate that vaccine-induced CD8+ T cell responses can control replication of heterologous challenge viruses

CD8+ T Cells from SIV Elite Controller Macaques Recognize Mamu-B*08-Bound Epitopes and Select for Widespread Viral Variation

Background. It is generally accepted that CD8(+) T cell responses play an important role in control of immunodeficiency virus replication. the association of HLA-B27 and -B57 with control of viremia supports this conclusion. However, specific correlates of viral control in individuals expressing these alleles have been difficult to define. We recently reported that transient in vivo CD8(+) cell depletion in simian immunodeficiency virus (SIV)-infected elite controller (EC) macaques resulted in a brief period of viral recrudescence. SIV replication was rapidly controlled with the reappearance of CD8(+) cells, implicating that these cells actively suppress viral replication in ECs. Methods and Findings. Here we show that three ECs in that study made at least seven robust CD8(+) T cell responses directed against novel epitopes in Vif, Rev, and Nef restricted by the MHC class I molecule Mamu-B*08. Two of these Mamu-B*08-positive animals subsequently lost control of SIV replication. Their breakthrough virus harbored substitutions in multiple Mamu-B*08-restricted epitopes. Indeed, we found evidence for selection pressure mediated by Mamu-B*08-restricted CD8(+) T cells in all of the newly identified epitopes in a cohort of chronically infected macaques. Conclusions. Together, our data suggest that Mamu-B*08-restricted CD8(+) T cell responses effectively control replication of pathogenic SIV(mac)239. All seven regions encoding Mamu-B*08-restricted CD8(+) T cell epitopes also exhibit amino acid replacements typically seen only in the presence of Mamu-B*08, suggesting that the variation we observe is indeed selected by CD8(+) T cell responses. SIVmac239 infection of Indian rhesus macaques expressing Mamu-B*08 may therefore provide an animal model for understanding CD8(+) T cell-mediated control of HIV replication in humans.National Institutes of Health (NIH)National Center for Research Resources (NCRR)Japan Health Sciences FoundationKent State University Research CouncilOhio Board of Regents Research ChallengeResearch Facilities ImprovementUniv Wisconsin, WNPRC, Madison, WI 53706 USAUniversidade Federal de São Paulo, Div Infect Dis, São Paulo, BrazilUniv Wisconsin, Dept Pathol & Lab Med, Madison, WI USALa Jolla Inst Allergy & Immunol, Div Vaccine Discovery, La Jolla, CA USAUniv Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, Oxford OX3 9DU, EnglandKent State Univ, Dept Biol Sci, Kent, OH 44242 USAUniv S Carolina, Dept Biol Sci, Columbia, SC 29208 USAUniversidade Federal de São Paulo, Div Infect Dis, São Paulo, BrazilNational Institutes of Health (NIH): HHSN266200400088CNational Institutes of Health (NIH): R01 AI049120National Institutes of Health (NIH): R01 AI052056National Institutes of Health (NIH): R24 RR015371National Institutes of Health (NIH): R24 RR016038National Institutes of Health (NIH): R21 AI068586National Center for Research Resources (NCRR): P51 RR000167Japan Health Sciences Foundation: GM43940Research Facilities Improvement: RR15459-01Research Facilities Improvement: RR020141-01Web of Scienc