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Biology subjects

Mangold, S.

Publications and source records attributed to Mangold, S..

3 recordsLinked to original sources

Cross-fostering reveals that acoustic communication during parental care alleviates prenatal disadvantages in beetle offspring

Acoustic communication plays an important role in social interactions for many animals. It is used in a broad range of behaviours, such as parental care. Acoustic communication is also involved in the brood care of Nicrophorus vespilloides (HERBST 1783), which, together with the other burying beetles, are one of the rare exceptions among insects in that they practice biparental brood care. Previous studies showed that a lack of acoustic communication in burying beetles negatively affects the weight and survival rate of their offspring (Conrad et al. 2024). However, it remained unclear whether these results were mainly based on prenatal or postnatal effects of silencing. Therefore, in this study we wanted to find out whether negative effects on N. vespilloides larvae, which are due to a lack of prenatal acoustic communication between the parents, can be compensated by the postnatal brood care of stridulating foster parents. For this purpose, we applied parafilm on the pars stridens of some beetle pairs so that they could no longer stridulate. In a 2x2 cross-fostering experiment, larvae originating from silenced or stridulating parents were reared by either silenced or stridulating foster parents. The larvae of silenced parents showed a lower hatching weight than the larvae of control parents. At dispersal, larvae with stridulating original and foster parents were significantly heavier than those reared by silenced foster parents, from either origin. At dispersal, larvae with stridulating original and foster parents were significantly heavier than those reared by silenced foster parents, from either origin. Thus, the stridulating foster parents were apparently able to partially compensate the initial weight deficits of the larvae from silenced original parents. There were no effects of silencing on offspring survival. Our experiment demonstrates that post-hatching acoustic communication during brood care of N. vespilloides is of greater importance for larval growth than pre-hatching acoustic communication. Still, the inability to stridulate compromises the quality of both prenatal and postnatal care. It is conceivable that the acoustic communication of the parents provides orientation for the larvae when feeding, or that the adults coordinate their tasks and negotiate their parental investment. Our findings contribute further to our understanding of the function of parental communication during brood care.

animal behavior and cognition↗

Multi-specific DARPin(R) therapeutics demonstrate very high potency against mutated SARS-CoV-2 variants in vitro

SARS-CoV-2 has infected millions of people globally and continues to undergo evolution. Emerging variants can be partially resistant to vaccine induced immunity and therapeutic antibodies, emphasizing the urgent need for accessible, broad-spectrum therapeutics. Here, we report a comprehensive study of ensovibep, the first trispecific clinical DARPin candidate, that can simultaneously engage all three units of the spike protein trimer to potently inhibit ACE2 interaction, as revealed by structural analyses. The cooperative binding of the individual modules enables ensovibep to retain inhibitory potency against all frequent SARS-CoV-2 variants, including Omicron BA.1 and BA.2, as of February 2022. Moreover, viral passaging experiments show that ensovibep, when used as a single agent, can prevent development of escape mutations comparably to a cocktail of monoclonal antibodies (mAb). Finally, we demonstrate that the very high in vitro antiviral potency also translates into significant therapeutic protection and reduction of pathogenesis in Roborovski dwarf hamsters infected with either the SARS-CoV-2 wild-type or the Alpha variant. In this model, ensovibep prevents fatality and provides substantial protection equivalent to the standard of care mAb cocktail. These results support further clinical evaluation and indicate that ensovibep could be a valuable alternative to mAb cocktails and other treatments for COVID-19.

immunology↗

Highly potent anti-SARS-CoV-2 multi-DARPin therapeutic candidates

Globally accessible therapeutics against SARS-CoV-2 are urgently needed. Here, we report the generation of the first anti-SARS-CoV-2 DARPin molecules with therapeutic potential as well as rapid large-scale production capabilities. Highly potent multivalent DARPin molecules with low picomolar virus neutralization efficacies were generated by molecular linkage of three different monovalent DARPin molecules. These multivalent DARPin molecules target various domains of the SARS-CoV-2 spike protein, thereby limiting possible viral escape. Cryo-EM analysis of individual monovalent DARPin molecules provided structural explanations for the mode of action. Analysis of the protective efficacy of one multivalent DARPin molecule in a hamster SARS-CoV-2 infection model demonstrated a significant reduction of pathogenesis. Taken together, the multivalent DARPin molecules reported here, one of which has entered clinical studies, constitute promising therapeutics against the COVID-19 pandemic.

immunology↗