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Abstract 5‐Methylcytosine (5mC) is the central epigenetic mark of mammalian DNA, and plays fundamental roles in chromatin regulation. 5mC is dynamically read and translated into regulatory outputs by methyl‐CpG‐binding domain (MBD) proteins. These multidomain readers recognize 5mC via an MBD domain, and undergo additional domain‐dependent interactions with multiple additional chromatin components. However, studying this dynamic process is limited by a lack of methods to conditionally control the 5mC affinity of MBD readers in cells. Light‐control of MBD association to chromatin by genetically encoding a photocaged serine at the MBD‐DNA interface is reported. The authors study the association of MBD1 to mouse pericentromeres, dependent on its CxxC3 and transcriptional repressor domains (TRD) which interact with unmethylated CpG and heterochromatin‐associated complexes, respectively. Both domains significantly modulate association kinetics, arguing for a model in which the CxxC3 delays methylation responses of MBD1 by holding it at unmethylated loci, whereas the TRD promotes responses by aiding heterochromatin association is studied. Their approach offers otherwise inaccessible kinetic insights into the domain‐specific regulation of a central MBD reader, and sets the basis for further unravelling how the integration of MBDs into complex heterochromatin interaction networks control the kinetics of 5mC reading and translation into altered chromatin states.

The venom of Latrodectus spiders contains seven Latrotoxins (LaTXs), among them α-latrocrustatoxin (LCT) and δ- latroinsectotoxins δ-LIT. LaTXs bind to specific receptors on the surface of neuronal cells and target the molecular exocytosis machinery. Here, the authors present the cryo-EM structure of the α-LCT monomer and the δ-LIT dimer, which reveal that LaTXs are organized in four domains and they discuss the potential oligomerisation mechanism that takes place before LaTXs membrane insertion. Both recombinant α-LCT and δ-LIT form channels in artificial membrane bilayers, that are stabilized by Ca2+ ions.

This paper addresses the development of performance-based assessment items for ICT skills, skills in dealing with information and communication technologies, a construct which is rather broadly and only operationally defined. Item development followed a construct-driven approach to ensure that test scores could be interpreted as intended. Specifically, ICT-specific knowledge as well as problem-solving and the comprehension of text and graphics were defined as components of ICT skills and cognitive ICT tasks (i.e., accessing, managing, integrating, evaluating, creating). In order to capture the construct in a valid way, design principles for constructing the simulation environment and response format were formulated. To empirically evaluate the very heterogeneous items and detect malfunctioning items, item difficulties were analyzed and behavior-related indicators with item-specific thresholds were developed and applied. The 69 item’s difficulty scores from the Rasch model fell within a comparable range for each cognitive task. Process indicators addressing time use and test-taker interactions were used to analyze whether most test-takers executed the intended processes, exhibited disengagement, or got lost among the items. Most items were capable of eliciting the intended behavior; for the few exceptions, conclusions for item revisions were drawn. The results affirm the utility of the proposed framework for developing and implementing performance-based items to assess ICT skills.

A validity approach is proposed that uses processing times to collect validity evidence for the construct interpretation of test scores. The rationale of the approach is based on current research of processing times and on classical validity approaches, providing validity evidence based on relationships with other variables. Within the new approach, convergent validity evidence is obtained if a component skill, that is expected to underlie the task solution process in the target construct, positively moderates the relationship between effective speed and effective ability in the corresponding target construct. Discriminant validity evidence is provided if a component skill, that is not expected to underlie the task solution process in the target construct, does indeed not moderate the speed-ability relation in this target construct. Using data from a study that follows up the German PIAAC sample, this approach was applied to reading competence, assessed with PIAAC literacy items, and to quantitative reasoning, assessed with Number Series. As expected from theory, the effect of speed on ability in the target construct was only moderated by the respective underlying component skill, that is, word meaning activation skill as an underlying component skill of reading competence, and perceptual speed as an underlying component skill of reasoning. Accordingly, no positive interactions were found for the component skill that should not underlie the task solution process, that is, word meaning activation for reasoning and perceptual speed for reading. Furthermore, the study shows the suitability of the proposed validation approach. The use of time information in association with task results brings construct validation closer to the actual response process than widely used correlations of test scores.