R∞R_{\infty}-property for groups commensurable to nilpotent quotients of RAAGs

Let $G$ be a group and $\varphi$ an automorphism of $G$. Two elements $x,y \in G$ are said to be $\varphi$-conjugate if there exists a third element $z \in G$ such that $z x \varphi(z)^{-1} = y$. Being $\varphi$-conjugate defines an equivalence relation on $G$. The group $G$ is said to have the $R_{\infty}$-property if all its automorphisms $\varphi$ have infinitely many $\varphi$-conjugacy classes. For finitely generated torsion-free nilpotent groups, the so-called Mal'cev completion of the group is a useful tool in studying this property. Two groups have isomorphic Mal'cev completions if and only if they are abstractly commensurable. This raises the question whether the $R_{\infty}$-property is invariant under abstract commensurability within the class of finitely generated torsion-free nilpotent groups. We show that the answer to this question is negative and provide counterexamples within a class of 2-step nilpotent groups associated to edge-weighted graphs. These groups are commensurable to 2-step nilpotent quotients of right-angled Artin groups.Comment: 25 page

Systematic analysis of the kalimantacin assembly line NRPS module using an adapted targeted mutagenesis approach

Kalimantacin is an antimicrobial compound with strong antistaphylococcal activity that is produced by a hybrid trans-acyltransferase polyketide synthase/nonribosomal peptide synthetase system in Pseudomonas fluorescens BCCM_ID9359. We here present a systematic analysis of the substrate specificity of the glycine-incorporating adenylation domain from the kalimantacin biosynthetic assembly line by a targeted mutagenesis approach. The specificity-conferring code was adapted for use in Pseudomonas and mutated adenylation domain active site sequences were introduced in the kalimantacin gene cluster, using a newly adapted ligation independent cloning method. Antimicrobial activity screens and LC-MS analyses revealed that the production of the kalimantacin analogues in the mutated strains was abolished. These results support the idea that further insight in the specificity of downstream domains in nonribosomal peptide synthetases and polyketide synthases is required to efficiently engineer these strains in vivo

Understanding child and adolescent cyberbullying

Global development of digital technologies has provided considerable connectivity benefits. However, connectivity of this scale has presented a seemingly unmanageable number of potential risks to psychological harm especially experienced by children and adolescents; one such risk is cyberbullying. This chapter will initially address the origins of bullying, leading into an overview of cyberbullying. A review of the unique characteristics of online communication will shed light on the ongoing debate concerning cyberbullying being potentially more than an extension of traditional bullying. Current research findings encompassing prevalence, types of behavior, consequences, and the roles within cyberbullying activity will be discussed to guide future interventions to reduce the risk of vulnerability for children and adolescents. In parallel, this chapter also considers the relative and perhaps distorted risk perception that young people have of becoming a cybervictim. Finally, this chapter acknowledges current understanding to support future digital and social evolvement.N/

Unravelling the biosynthesis and mode of action of specialized metabolites

Since decades, the excessive use of antibiotics has led to an enormous spread of multi-drug resistant (MDR) bacteria. Therefore, researchers show renewed interests in natural antibiotics, like secondary metabolites, as potential source of new drugs. Secondary metabolites are synthesized by large enzymatic assembly lines. Past years, researchers wanted to create new hybrid lines, thereby trying to expand the natural antibiotics pool. However, to date, attempts to assemble new pathways have not been a great success. Many times, production of new metabolites was completely abolished. An important explanation for these problems is the lack of knowledge about protein interactions, necessary to connect the different domains and modules. This PhD project aims to create new tools to combat the spread and danger of MDR bacteria. This will be realized by identifying protein interactions present in secondary metabolite assembly lines, followed by the development of an innovative domain assembly approach based on the acquired insights on protein interactions. The ultimate goal of this research is the development of new antibacterial molecules, ready for (pre)clinical testing.status: publishe

A Protein Interaction Map of the Kalimantacin Biosynthesis Assembly Line

The antimicrobial secondary metabolite kalimantacin (also called batumin) is produced by a hybrid polyketide/non-ribosomal peptide system in Pseudomonas fluorescens BCCM_ID9359. In this study, the kalimantacin biosynthesis gene cluster is analyzed by yeast two-hybrid analysis, creating a protein-protein interaction map of the entire assembly line. In total, 28 potential interactions were identified, of which 13 could be confirmed further. These interactions include the dimerization of ketosynthase domains, a link between assembly line modules 9 and 10, and a specific interaction between the trans-acting enoyl reductase BatK and the carrier proteins of modules 8 and 10. These interactions reveal fundamental insight into the biosynthesis of secondary metabolites. This study is the first to reveal interactions in a complete biosynthetic pathway. Similar future studies could build a strong basis for engineering strategies in such clusters.status: publishe

A protein interaction map of the kalimantacin biosynthesis assembly line

The antimicrobial secondary metabolite kalimantacin is produced by a hybrid polyketide/ non-ribosomal peptide system in Pseudomonas fluorescens BCCM_ID9359. In this study, the kalimantacin biosynthesis gene cluster is analyzed by yeast two-hybrid analysis, creating a protein-protein interaction map of the entire assembly line. In total, 28 potential interactions were identified, of which 13 could be confirmed further. These interactions include the dimerization of ketosynthase domains, a link between assembly line modules 9 and 10, and a specific interaction between the trans-acting enoyl reductase BatK and the carrier proteins of modules 8 and 10. These interactions reveal fundamental insight into the biosynthesis of secondary metabolites.This study is the first to reveal interactions in a complete biosynthetic pathway. Similar future studies could build a strong basis for engineering strategies in such clusters

Systematic analysis of the kalimantacin assembly line NRPS module using an adapted targeted mutagenesis approach

Kalimantacin is an antimicrobial compound with strong antistaphylococcal activity that is produced by a hybrid trans-acyltransferase polyketide synthase/nonribosomal peptide synthetase system in Pseudomonas fluorescens BCCM_ID9359. We here present a systematic analysis of the substrate specificity of the glycine-incorporating adenylation domain from the kalimantacin biosynthetic assembly line by a targeted mutagenesis approach. The specificity-conferring code was adapted for use in Pseudomonas and mutated adenylation domain active site sequences were introduced in the kalimantacin gene cluster, using a newly adapted ligation independent cloning method. Antimicrobial activity screens and LC-MS analyses revealed that the production of the kalimantacin analogues in the mutated strains was abolished. These results support the idea that further insight in the specificity of downstream domains in nonribosomal peptide synthetases and polyketide synthases is required to efficiently engineer these strains in vivo.status: publishe