The genetic architecture underlying prey-dependent performance in a microbial predator

Natural selection should favour generalist predators that outperform specialists across all prey types. Two genetic solutions could explain why intraspecific variation in predatory performance is, nonetheless, widespread: mutations beneficial on one prey type are costly on another (antagonistic pleiotropy), or mutational effects are prey-specific, which weakens selection, allowing variation to persist (relaxed selection). To understand the relative importance of these alternatives, we characterised natural variation in predatory performance in the microbial predator Dictyostelium discoideum. We found widespread nontransitive differences among strains in predatory success across different bacterial prey, which can facilitate stain coexistence in multi-prey environments. To understand the genetic basis, we developed methods for high throughput experimental evolution on different prey (REMI-seq). Most mutations (~77%) had prey-specific effects, with very few (~4%) showing antagonistic pleiotropy. This highlights the potential for prey-specific effects to dilute selection, which would inhibit the purging of variation and prevent the emergence of an optimal generalist predator.

The Effects of Tobacco Coverage in the Public Communication Environment on Young People’s Decisions to Smoke Combustible Cigarettes

In today’s complex media environment, does media coverage influence youth and young adults’ (YYA) tobacco use and intentions? We conceptualize the “public communication environment” and effect mediators, then ask whether over time variation in exogenously measured tobacco media coverage from mass and social media sources predicts daily YYA cigarette smoking intentions measured in a rolling nationally representative phone survey (N = 11,847 on 1,147 days between May 2014 and June 2017). Past week anti-tobacco and pro-tobacco content from Twitter, newspapers, broadcast news, Associated Press, and web blogs made coherent scales (thetas = 0.77 and 0.79). Opportunities for exposure to anti-tobacco content in the past week predicted lower intentions to smoke (Odds ratio [OR] = 0.95, p < .05, 95% confidence interval [CI] = 0.91–1.00). The effect was stronger among current smokers than among nonsmokers (interaction OR = 0.88, p < .05, 95% CI = 0.77–1.00). These findings support specific effects of anti-tobacco media coverage and illustrate a productive general approach to conceptualizing and assessing effects in the complex media environment.

Specific gut bacterial responses to natural diets of tropical birds

The composition of gut bacterial communities is strongly influenced by the host diet in many animal taxa. For birds, the effect of diet on the microbiomes has been documented through diet manipulation studies. However, for wild birds, most studies have drawn on literature-based information to decipher the dietary effects, thereby, overlooking individual variation in dietary intake. Here we examine how naturally consumed diets influence the composition of the crop and cloacal microbiomes of twenty-one tropical bird species, using visual and metabarcoding-based identification of consumed diets and bacterial 16S rRNA microbiome sequencing. We show that diet intakes vary markedly between individuals of the same species and that literature-based dietary guilds grossly underestimate intraspecific diet variability. Furthermore, despite an effect of literature-based dietary guild assignment of host taxa, the composition of natural diets does not align with crop and cloacal microbiome similarity. However, host-taxon specific gut bacterial lineages are positively correlated with specific diet items, indicating that certain microbes associate with different diet components in specific avian hosts. Consequently, microbiome composition is not congruent with the overall consumed diet composition of species, but specific components of a consumed diet lead to host-specific effects on gut bacterial taxa.

Paris–Rome–London. Information and Propaganda Campaign for the Polish Question prior to the Great War (1907–14)

The article reconstructs Polish information and propaganda campaigns in Western Europe in the run-up to the Great War. Those initiatives allowed the issues related to the Polish question, especially the persecution of Poles under the Prussian and Russian partitions, to be brought to public attention in the West. The authors trace the process of disseminating information to the intellectual communities of Paris, Rome and London based on participant accounts, reports, propaganda pamphlets, the press from the period and secondary literature. They conclude that propaganda campaigns reached a relatively narrow group of intellectuals, writers, members of the artistic community, journalists, and to a lesser extent, parliamentarians. Although the information campaign could not immediately alter the previously established stereotypes, its specific effects could be observed during the Great War and at the Paris Peace Conference.

Proteome-wide Mendelian randomization in global biobank meta-analysis reveals multi-ancestry drug targets for common diseases

Proteome-wide Mendelian randomization (MR) shows value in prioritizing drug targets in Europeans, but limited data has made identification of causal proteins in other ancestries challenging. Here we present a multi-ancestry proteome-wide MR analysis pipeline based on cross-population data from the Global Biobank Meta-analysis Initiative (GBMI). We estimated the causal effects of 1,545 proteins on eight complex diseases in up to 32,658 individuals of African ancestries and 1.22 million individuals of European ancestries. We identified 45 and seven protein-disease pairs with MR and genetic colocalization evidence in the two ancestries respectively. 15 protein-disease pairs showed evidence of differential effects between males and females. A multi-ancestry MR comparison identified two protein-disease pairs with MR evidence of an effect in both ancestries, seven pairs with European-specific effects and seven with African-specific effects. Integrating these MR signals with observational and clinical trial evidence, we were able to evaluate the efficacy of one existing drug, identify seven drug repurposing opportunities and predict seven novel effects of proteins on diseases. Our results highlight the value of proteome-wide MR in informing the generalisability of drug targets across ancestries and illustrate the value of multi-cohort and biobank meta-analysis of genetic data for drug development.

Image based annotation of Chemogenomic Libraries for Phenotypic Screening

Phenotypical screening is a widely used approach in drug discovery for the identification of small molecules with cellular activities. However, functional annotation of identified hits often poses a challenge. The development of small molecules with narrow or exclusive target selectivity such as chemical probes and chemogenomic (CG) libraries, greatly diminishes this challenge, but non-specific effects caused by compound toxicity or interference with basic cellular functions still poses a problem to associate phenotypic readouts with molecular targets. Hence, each compound should ideally be comprehensively characterized regarding its effects on general cell functions. Here, we report an optimized live-cell multiplexed assay that classifies cells based on nuclear morphology, presenting an excellent indicator for cellular responses such as early apoptosis and necrosis. This basic readout in combination with the detection of other general cell damaging activities of small molecules such as changes in cytoskeletal morphology, cell cycle and mitochondrial health provides a comprehensive time-dependent characterization of the effect of small molecules on cellular health in a single experiment. The developed high-content assay offers multi-dimensional comprehensive characterization that can be used to delineate generic effects regarding cell functions and cell viability, allowing an assessment of compound suitability for subsequent detailed phenotypic and mechanistic studies.

Epitope-Specific Anti-C1q Autoantibodies in Systemic Lupus Erythematosus

ObjectiveIn patients with systemic lupus erythematosus (SLE) complement C1q is frequently targeted by autoantibodies (anti-C1q), that correlate best with active renal disease. Anti-C1q bind to largely unknown epitopes on the collagen-like region (CLR) of this highly functional molecule. Here we aimed at exploring the role of epitope-specific anti-C1q in SLE patients.MethodsFirst, 22 sera of SLE patients, healthy controls and anti-C1q positive patients without SLE were screened for anti-C1q epitopes by a PEPperMAP® microarray, expressing CLR of C1q derived peptides with one amino acid (AA) shift in different lengths and conformations. Afterwards, samples of 378 SLE patients and 100 healthy blood donors were analyzed for antibodies against the identified epitopes by peptide-based ELISA. Relationships between peptide-specific autoantibodies and SLE disease manifestations were explored by logistic regression models.ResultsThe epitope mapping showed increased IgG binding to three peptides of the C1q A- and three of the C1q B-chain. In subsequent peptide-based ELISAs, SLE sera showed significantly higher binding to two N-terminally located C1q A-chain peptides than controls (p < 0.0001), but not to the other peptides. While anti-C1q were associated with a broad spectrum of disease manifestations, some of the peptide-antibodies were associated with selected disease manifestations, and antibodies against the N-terminal C1q A-chain showed a stronger discrimination between SLE and controls than conventional anti-C1q.ConclusionIn this large explorative study anti-C1q correlate with SLE overall disease activity. In contrast, peptide-antibodies are associated with specific aspects of the disease suggesting epitope-specific effects of anti-C1q in patients with SLE.

Association of SIX1-SIX6 polymorphisms with peripapillary retinal nerve fibre layer thickness in children

PurposeAssociation of SIX1-SIX6 variants with peripapillary retinal nerve fibre layer (p-RNFL) thickness had been reported in adults. This study aimed to investigate these associations in children, with further explorations by spatial, age and sex stratifications.Methods2878 school children aged between 6 and 9 years were enrolled from the Hong Kong Children Eye Study. Three single-nucleotide polymorphisms (SNPs) at the SIX1-SIX6 locus were genotyped. The association of each SNP with p-RNFL thickness (including global and sectoral thickness) were evaluated using multiple linear regression.ResultsSNPs rs33912345 (p=7.7×10−4) and rs10483727 (p=0.0013) showed significant associations with temporal-inferior p-RNFL thickness. The C allele of rs33912345 was associated with a thinner temporal-inferior p-RNFL by an average of 2.44 µm, while rs10483727-T was associated with a thinner temporal-inferior p-RNFL by 2.32 µm. The association with temporal-inferior p-RNFL was the strongest in the 8–9 year-old group for rs33912345 (p=5.2×10−4) and rs10483727 (p=3.3×10−4). Both SNPs were significantly associated with temporal-inferior p-RNFL thickness in boys (p<0.0017), but not in girls (p>0.05). In contrast, rs12436579-C (β=1.66; p=0.0059), but not rs33912345-C (β=1.31; p=0.052) or rs10483727-T (β=1.19; p=0.078), was nominally associated with a thicker nasal-inferior p-RNFL.ConclusionsBoth rs33912345 and rs10483727 at SIX1-SIX6 were associated with p-RNFL thickness in children, especially at the temporal-inferior sector, with age-dependent and sex-specific effects. SNP rs12436579 was associated with nasal-inferior p-RNFL thickness. Our findings suggested a role of SIX1-SIX6 in RNFL variation during neural retina development in childhood.

Dominance in humans

Dominance captures behavioural patterns found in social hierarchies that arise from agonistic interactions in which some individuals coercively exploit their control over costs and benefits to extract deference from others, often through aggression, threats and/or intimidation. Accumulating evidence points to its importance in humans and its separation from prestige—an alternate avenue to high status in which status arises from information (e.g. knowledge, skill, etc.) or other non-rival goods. In this review, we provide an overview of the theoretical underpinnings of dominance as a concept within evolutionary biology, discuss the challenges of applying it to humans and consider alternative theoretical accounts which assert that dominance is relevant to understanding status in humans. We then review empirical evidence for its continued importance in human groups, including the effects of dominance—independently of prestige—on measurable outcomes such as social influence and reproductive fitness, evidence for specialized dominance psychology, and evidence for gender-specific effects. Finally, because human-specific factors such as norms and coalitions may place bounds on purely coercive status-attainment strategies, we end by considering key situations and contexts that increase the likelihood for dominance status to coexist alongside prestige status within the same individual, including how: (i) institutional power and authority tend to elicit dominance; (ii) dominance-enhancing traits can at times generate benefits for others (prestige); and (iii) certain dominance cues and ethology may lead to mis-attributions of prestige. This article is part of the theme issue ‘The centennial of the pecking order: current state and future prospects for the study of dominance hierarchies’.