Anopheline salivary protein genes and gene families: an evolutionary overview after the whole genome sequence of sixteen Anopheles species

Background: Mosquito saliva is a complex cocktail whose pharmacological properties play an essential role in blood feeding by counteracting host physiological response to tissue injury. Moreover, vector borne pathogens are transmitted to vertebrates and exposed to their immune system in the context of mosquito saliva which, in virtue of its immunomodulatory properties, can modify the local environment at the feeding site and eventually affect pathogen transmission. In addition, the host antibody response to salivary proteins may be used to assess human exposure to mosquito vectors. Even though the role of quite a few mosquito salivary proteins has been clarified in the last decade, we still completely ignore the physiological role of many of them as well as the extent of their involvement in the complex interactions taking place between the mosquito vectors, the pathogens they transmit and the vertebrate host. The recent release of the genomes of 16 Anopheles species offered the opportunity to get insights into function and evolution of salivary protein families in anopheline mosquitoes. Results: Orthologues of fifty three Anopheles gambiae salivary proteins were retrieved and annotated from 18 additional anopheline species belonging to the three subgenera Cellia, Anopheles, and Nyssorhynchus. Our analysis included 824 full-length salivary proteins from 24 different families and allowed the identification of 79 novel salivary genes and re-annotation of 379 wrong predictions. The comparative, structural and phylogenetic analyses yielded an unprecedented view of the anopheline salivary repertoires and of their evolution over 100 million years of anopheline radiation shedding light on mechanisms and evolutionary forces that contributed shaping the anopheline sialomes. Conclusions: We provide here a comprehensive description, classification and evolutionary overview of the main anopheline salivary protein families and identify two novel candidate markers of human exposure to malaria vectors worldwide. This anopheline sialome catalogue, which is easily accessible as hyperlinked spreadsheet, is expected to be useful to the vector biology community and to improve the capacity to gain a deeper understanding of mosquito salivary proteins facilitating their possible exploitation for epidemiological and/or pathogen-vector-host interaction studies

A missing dimension in measures of vaccination impacts

Immunological protection, acquired from either natural infection or vaccination, varies among hosts, reflecting underlying biological variation and affecting population-level protection. Owing to the nature of resistance mechanisms, distributions of susceptibility and protection entangle with pathogen dose in a way that can be decoupled by adequately representing the dose dimension. Any infectious processes must depend in some fashion on dose, and empirical evidence exists for an effect of exposure dose on the probability of transmission to mumps-vaccinated hosts [1], the case-fatality ratio of measles [2], and the probability of infection and, given infection, of symptoms in cholera [3]. Extreme distributions of vaccine protection have been termed leaky (partially protects all hosts) and all-or-nothing (totally protects a proportion of hosts) [4]. These distributions can be distinguished in vaccine field trials from the time dependence of infections [5]. Frailty mixing models have also been proposed to estimate the distribution of protection from time to event data [6], [7], although the results are not comparable across regions unless there is explicit control for baseline transmission [8]. Distributions of host susceptibility and acquired protection can be estimated from dose-response data generated under controlled experimental conditions [9]–[11] and natural settings [12], [13]. These distributions can guide research on mechanisms of protection, as well as enable model validity across the entire range of transmission intensities. We argue for a shift to a dose-dimension paradigm in infectious disease science and community health

Cost-Effectiveness of Genotype Testing for Primary Resistance in Brazil

Objective: HIV genotype-resistance testing can help identify more effective antiretroviral treatment (ART) regimens for patients, substantially increasing the likelihood of viral suppression and immune recovery. We sought to evaluate the cost-effectiveness of genotype-resistance testing before first-line ART initiation in Brazil. Design: We used a previously published microsimulation model of HIV disease (CEPAC-International) and data from Brazil to compare the clinical impact, costs, and cost-effectiveness of initial genotype testing (Genotype) with no initial genotype testing (No genotype). Methods: Model parameters were derived from the HIV Clinical Cohort at the Evandro Chagas Clinical Research Institute and from published data, using Brazilian sources whenever possible. Baseline patient characteristics included 69% male, mean age of 36 years (SD, 10 years), mean CD4 count of 347 per microliter (SD, 300/µL) at ART initiation, annual ART costs from 2012 US $1400 to US$13,400, genotype test cost of US $230, and primary resistance prevalence of 4.4$12,300. Results: Compared with No genotype, Genotype increased life expectancy from 18.45 to 18.47 years and reduced lifetime cost from US $45,000 to$44,770; thus, in the base case, Genotype was cost saving. Genotype was cost-effective at primary resistance prevalence as low as 1.4% and remained cost-effective when subsequent-line ART costs decreased to 30% of baseline value. Cost-inefficient results were observed only when simultaneously holding multiple parameters to extremes of their plausible ranges. Conclusions: Genotype-resistance testing in ART-naive individuals in Brazil will improve survival and decrease costs and should be incorporated into HIV treatment guidelines in Brazil

Are There Cross-Cultural Legal Principles? Modal Reasoning Uncovers Procedural Constraints on Law

Despite pervasive variation in the content of laws, legal theorists and anthropologists have argued that laws share certain abstract features and even speculated that law may be a human universal. In the present report, we evaluate this thesis through an experiment administered in 11 different countries. Are there cross-cultural principles of law? In a between-subjects design, participants (N = 3,054) were asked whether there could be laws that violate certain procedural principles (e.g., laws applied retrospectively or unintelligible laws), and also whether there are any such laws. Confirming our preregistered prediction, people reported that such laws cannot exist, but also (paradoxically) that there are such laws. These results document cross-culturally and –linguistically robust beliefs about the concept of law which defy people's grasp of how legal systems function in practice

Coordination and expertise foster legal textualism

Funding Information: ACKNOWLEDGMENTS. This research was supported by the Spanish Ministry of Science and Innovation (PID2020-119791RA-I00; RTI2018-098882-B-I00), the Polish National Science Centre (2020/36/C/HS5/00111; 2017/25/N/HS5/00944), the Swiss National Science Foundation (PZ00P1_179912), and the European Research Council (805498). Publisher Copyright: Copyright © 2022 the Author(s).A cross-cultural survey experiment revealed a dominant tendency to rely on a rule’s letter over its spirit when deciding which behaviors violate the rule. This tendency varied markedly across (k = 15) countries, owing to variation in the impact of moral appraisals on judgments of rule violation. Compared with laypeople, legal experts were more inclined to disregard their moral evaluations of the acts altogether and consequently exhibited stronger textualist tendencies. Finally, we evaluated a plausible mechanism for the emergence of textualism: in a two-player coordination game, incentives to coordinate in the absence of communication reinforced participants’ adherence to rules’ literal meaning. Together, these studies (total n = 5,794) help clarify the origins and allure of textualism, especially in the law. Within heterogeneous communities in which members diverge in their moral appraisals involving a rule’s purpose, the rule’s literal meaning provides a clear focal point—an identifiable point of agreement enabling coordinated interpretation among citizens, lawmakers, and judges.Peer reviewe

COVID-19 and social distancing among children and adolescents in Brazil

OBJECTIVE To estimate the prevalence of SARS-CoV-2 antibodies and the adherence to measures of social distancing in children and adolescents studied in three national surveys conducted in Brazil between May–June 2020. METHODS Three national serological surveys were conducted in 133 sentinel cities located in all 27 Federative Units. Multistage probability sampling was used to select 250 individuals per city. The total sample size in age ranges 0–9 and 10–19 years old are of 4,263 and 8,024 individuals, respectively. Information on children or adolescents was gathered with a data collection app, and a rapid point-of-case test for SARS-CoV-2 was conducted on a finger prick blood sample. RESULTS The adjusted prevalence of antibodies was 2.9% (2.2–3.6) among children 0–9 years, 2.2% (1.8–2.6) among adolescents 10-19 years, and 3.0% (2.7–3.3) among adults 20+years. Prevalence of antibodies was higher among poor children and adolescents compared to those of rich families. Adherence to social distancing measures was seen in 72.4% (71.9–73.8) of families with children, 60.8% (59.6–61.9) for adolescents, and 57.4% (56.9–57.8) for adults. For not leaving the house except for essential matters the proportions were 81.7% (80.5–82.9), 70.6% (69.6–61.9), and 65.1% (64.7–65.5), respectively. Among children and adolescents, social distancing was strongly associated with socioeconomic status, being much higher in the better-off families. CONCLUSIONS The prevalence of antibodies against SARS-CoV-2 showed comparable levels among children, adolescents, and adults. Adherence to social distancing measures was more prevalent in children, followed by adolescents. There were important socioeconomic differences in the adherence to social distancing among children and adolescents