Digit ratio (2D:4D) and social integration: an effect of prenatal sex hormones

The position people occupy in their social and professional networks is related to their social status and has strong effects on their access to social resources. While attainment of particular positions is driven by behavioral traits, many biological factors predispose individuals to certain behaviors and motivations. Prior work on exposure to fetal androgens (measured by second-to-fourth digit ratio, 2D:4D) shows that it correlates with behaviors and traits related to social status, which might make people more socially integrated. However, it also predicts certain anti-social behaviors and disorders associated with lower socialization. We explore whether 2D:4D correlates with network position later in life and find that individuals with low 2D:4D become more central in their social environment. Interestingly, low 2D:4D males are more likely to exhibit high betweenness centrality (they connect separated parts of the social structure) while low 2D:4D females are more likely to exhibit high in-degree centrality (more people name them as friends). These gender-specific differences are reinforced by transitivity (the likelihood that one’s friends are also friends with one another): neighbors of low 2D:4D men tend not to know each other; the contrary is observed for low 2D:4D women. Our results suggest that biological predispositions influence the organization of human societies and that exposure to prenatal androgens influences different status seeking behaviors in men and women

Hydrazones and Thiosemicarbazones Targeting Protein-Protein-Interactions of SARS-CoV-2 Papain-like Protease

The papain-like protease (PLpro) of SARS-CoV-2 is essential for viral propagation and, additionally, dysregulation of the host innate immune system. Using a library of 40 potential metal-chelating compounds we performed an X-ray crystallographic screening against PLpro. As outcome we identified six compounds binding to the target protein. Here we describe the interaction of one hydrazone (H1) and five thiosemicarbazone (T1-T5) compounds with the two distinct natural substrate binding sites of PLpro for ubiquitin and ISG15. H1 binds to a polar groove at the S1 binding site by forming several hydrogen bonds with PLpro. T1-T5 bind into a deep pocket close to the polyubiquitin and ISG15 binding site S2. Their interactions are mainly mediated by multiple hydrogen bonds and further hydrophobic interactions. In particular compound H1 interferes with natural substrate binding by sterical hindrance and induces conformational changes in protein residues involved in substrate binding, while compounds T1-T5 could have a more indirect effect. Fluorescence based enzyme activity assay and complementary thermal stability analysis reveal only weak inhibition properties in the high micromolar range thereby indicating the need for compound optimization. Nevertheless, the unique binding properties involving strong hydrogen bonding and the various options for structural optimization make the compounds ideal lead structures. In combination with the inexpensive and undemanding synthesis, the reported hydrazone and thiosemicarbazones represent an attractive scaffold for further structure-based development of novel PLpro inhibitors by interrupting protein-protein interactions at the S1 and S2 site

The aflatox® project: Approaching the development of new generation, natural‐based compounds for the containment of the mycotoxigenic phytopathogen Aspergillus flavus and aflatoxin contamination

The control of the fungal contamination on crops is considered a priority by the sanitary authorities of an increasing number of countries, and this is also due to the fact that the geographic areas interested in mycotoxin outbreaks are widening. Among the different pre‐ and post‐harvest strategies that may be applied to prevent fungal and/or aflatoxin contamination, fungicides still play a prominent role; however, despite of countless efforts, to date the problem of food and feed contamination remains unsolved, since the essential factors that affect aflatoxins production are various and hardly to handle as a whole. In this scenario, the exploitation of bioactive natural sources to obtain new agents presenting novel mechanisms of action may represent a successful strategy to minimize, at the same time, aflatoxin contamination and the use of toxic pesticides. The Aflatox® Project was aimed at the development of new‐generation inhibitors of aflatoxigenic Aspergillus spp. proliferation and toxin production, through the modification of naturally occurring molecules: a panel of 177 compounds, belonging to the thiosemicarbazones class, have been synthesized and screened for their antifungal and anti‐aflatoxigenic potential. The most effective compounds, selected as the best candidates as aflatoxin containment agents, were also evaluated in terms of cytotoxicity, genotoxicity and epi‐genotoxicity to exclude potential harmful effect on the human health, the plants on which fungi grow and the whole ecosystem

Photoinduced alkaline pH-jump on the nanosecond time scale

The triphenylmethane leucohydroxide salt 4-(dimethylamino)-4'-(trimethylammonium) triphenylmethanol iodide has been used as a photoactivatable caged hydroxide to rapidly increase the pH of a neutral aqueous solution on the nanosecond time scale. Photoexcitation of the compound with a nanosecond ultraviolet laser pulse results in the formation of a colored carbocation with a rate greater than 108 s-1; recombination occurs with a multiexponential kinetics. The dissociation is completely reversible on time scales of 102 s and offers a large time window after the pH jump, in which the proton transfer reactions can be studied. The effectiveness of the photodissociation process to increase the pH of the solution has been demonstrated by means of the pH indicator bromoxylenol blue