the paper and online samples (P=.12). Finally, the IRT analyses indicated negligible multidimensionality, insufficient subscale reliability after accounting for the eHEALS general factor, and a reduced subset of items that could serve as a unidimensional index of the eHEALS across the paper and online samples. CONCLUSIONS The German eHEALS evidenced good psychometric properties in a parent-specific study sample. Factor analyses indicated a strong general factor across purposively distinct sample frames (online and paper). IRT analyses validated the eHEALS as a unidimensional index while failing to find support for subscale usage. ©Sibylle Juvalta, Matthew J Kerry, Rebecca Jaks, Isabel Baumann, Julia Dratva. Originally published in the Journal of Medical Internet Research (http//www.jmir.org), 13.03.2020.Members of the Corynebacterineae suborder of Actinobacteria have a unique cell surface architecture and, unlike most well-studied bacteria, grow by tip-extension. To investigate the distinct morphogenic mechanisms shared by these organisms, we performed a genome-wide phenotypic profiling analysis using Corynebacterium glutamicum as a model. A high-density transposon mutagenized library was challenged with a panel of antibiotics and other stresses. The fitness of mutants in each gene under each condition was then assessed by transposon-sequencing. Clustering of the resulting phenotypic fingerprints revealed a role for several genes of previously unknown function in surface biogenesis. Further analysis identified CofA (Cgp_0016) as an interaction partner of the peptidoglycan synthase PBP1a that promotes its stable accumulation at sites of polar growth. The related Mycobacterium tuberculosis proteins were also found to interact, highlighting the utility of our dataset for uncovering conserved principles of morphogenesis for this clinically relevant bacterial suborder. © 2020, Sher et al.Injury to the newborn mouse heart is efficiently regenerated, but this capacity is lost by one week after birth. We found that IGF2, an important mitogen in heart development, is required for neonatal heart regeneration. IGF2 originates from the endocardium/endothelium and is transduced in cardiomyocytes by the insulin receptor. Following injury on postnatal day 1, absence of IGF2 abolished injury-induced cell cycle entry during the early part of the first postnatal week. Consequently, regeneration failed despite the later presence of additional cell cycle-inducing activities 7 days following injury. Most cardiomyocytes transition from mononuclear diploid to polyploid during the first postnatal week. Regeneration was rescued in Igf2-deficient neonates in three different contexts that elevate the percentage of mononuclear diploid cardiomyocytes beyond postnatal day 7. Thus, IGF2 is a paracrine-acting mitogen for heart regeneration during the early postnatal period, and IGF2-deficiency unmasks the dependence of this process on proliferation-competent mononuclear diploid cardiomyocytes. © 2020, Shen et al.The supramammillary nucleus (SuM) provides substantial innervation to the dentate gyrus (DG). It remains unknown how the SuM and DG coordinate their activities at the circuit level to regulate spatial memory. Additionally, SuM co-releases GABA and glutamate to the DG, but the relative role of GABA versus glutamate in regulating spatial memory remains unknown. Here we report that SuM-DG Ca2+ activities are highly correlated during spatial memory retrieval as compared to the moderate correlation during memory encoding when mice are performing a location discrimination task. Supporting this evidence, we demonstrate that the activity of SuM neurons or SuM-DG projections is required for spatial memory retrieval. Furthermore, we show that SuM glutamate transmission is necessary for both spatial memory retrieval and highly-correlated SuM-DG activities during spatial memory retrieval. Our studies identify a long-range SuM-DG circuit linking two highly correlated subcortical regions to regulate spatial memory retrieval through SuM glutamate release. © 2020, Li et al.Adaptive immunity vitally depends on major histocompatibility complex class I (MHC I) molecules loaded with peptides. Selective loading of peptides onto MHC I, referred to as peptide editing, is catalyzed by tapasin and the tapasin-related TAPBPR. An important catalytic role has been ascribed to a structural feature in TAPBPR called the scoop loop, but the exact function of the scoop loop remains elusive. Here, using a reconstituted system of defined peptide-exchange components including human TAPBPR variants, we uncover a substantial contribution of the scoop loop to the stability of the MHC I-chaperone complex and to peptide editing. We reveal that the scoop loop of TAPBPR functions as an internal peptide surrogate in peptide-depleted environments stabilizing empty MHC I and impeding peptide rebinding. The scoop loop thereby acts as an additional selectivity filter in shaping the repertoire of presented peptide epitopes and the formation of a hierarchical immune response. © 2020, Sagert et al.Ion selectivity is a defining feature of a given ion channel and is considered immutable. Here we show that ion selectivity of the lysosomal ion channel TPC2, which is hotly debated (Calcraft et al., 2009; Guo et al., 2017; Jha et al., 2014; Ruas et al., 2015; Wang et al., 2012), depends on the activating ligand. A high throughput screen identified two structurally distinct TPC2 agonists. One of these evoked robust Ca2+-signals and non-selective cation currents, the other weaker Ca2+-signals and Na+-selective currents. These properties were mirrored by the Ca2+-mobilizing messenger, NAADP and the phosphoinositide, PI(3,5)P2, respectively. Agonist action was differentially inhibited by mutation of a single TPC2 residue and coupled to opposing changes in lysosomal pH and exocytosis. Our findings resolve conflicting reports on the permeability and gating properties of TPC2 and they establish a new paradigm whereby a single ion channel mediates distinct, functionally-relevant ionic signatures on demand. © 2020, Gerndt et al.A study of 3,500 children in the UK shows that data on socioeconomic background and previous educational achievements can better predict how students will perform at school than genetic data. © 2020, Janssens.FANCI FANCD2 monoubiquitination is a critical event for replication fork stabilization by the Fanconi anemia (FA) DNA repair pathway. It has been proposed that at stalled replication forks, monoubiquitinated-FANCD2 serves to recruit DNA repair proteins that contain ubiquitin-binding motifs. Here we have reconstituted the FA pathway in vitro to study functional consequences of FANCIFANCD2 monoubiquitination. We report that monoubiquitination does not promote any specific exogenous proteinprotein interactions, but instead stabilizes FANCIFANCD2 heterodimers on dsDNA. This clamping requires monoubiquitination of only the FANCD2 subunit. We further show that purified monoubiquitinated FANCIFANCD2 forms filament-like arrays on long dsDNA using electron microscopy. Our results reveal how monoubiquitinated FANCIFANCD2, defective in many cancer types and all cases of FA, is activated upon DNA binding. © 2020, Tan et al.The hippocampus supports memory encoding and retrieval, which may occur at distinct phases of the theta cycle. These processes dynamically interact over rapid timescales, especially when sensory information conflicts with memory. The ability to link hippocampal dynamics to memory-guided behaviors has been limited by experiments that lack the temporal resolution to segregate encoding and retrieval. Here, we simultaneously tracked eye movements and hippocampal field potentials while neurosurgical patients performed a spatial memory task. Phase-locking at the peak of theta preceded fixations to retrieved locations, indicating that the hippocampus coordinates memory-guided eye movements. In contrast, phase-locking at the trough of theta followed fixations to novel object-locations and predicted intact memory of the original location. Theta-gamma phase amplitude coupling increased during fixations to conflicting visual content, but predicted memory updating. Hippocampal theta thus supports learning through two interleaved processes strengthening encoding of novel information and guiding exploration based on prior experience. © 2020, Kragel et al.A prevalent model is that sharp-wave ripples (SWR) arise 'spontaneously’ in CA3 and propagate recent memory traces outward to the neocortex to facilitate memory consolidation there. Using voltage and extracellular glutamate transient recording over widespread regions of mice dorsal neocortex in relation to CA1 multiunit activity (MUA) and SWR, we find that the largest SWR-related modulation occurs in retrosplenial cortex; however, contrary to the unidirectional hypothesis, neocortical activation exhibited a continuum of activation timings relative to SWRs, varying from leading to lagging. Thus, contrary to the model in which SWRs arise 'spontaneously’ in the hippocampus, neocortical activation often precedes SWRs and may thus constitute a trigger event in which neocortical information seeds associative reactivation of hippocampal 'indices’. This timing continuum is consistent with a dynamics in which older, more consolidated memories may in fact initiate the hippocampal-neocortical dialog, whereas reactivation of newer memories may be initiated predominantly in the hippocampus. © 2020, Karimi Abadchi et al.Every cell is protected by a semipermeable membrane. Peptides with the right properties, for example Antimicrobial peptides (AMPs), can disrupt this protective barrier by formation of leaky pores. Unfortunately, matching peptide properties with their ability to selectively form pores in bacterial membranes remains elusive. In particular, the proline/glycine kink in helical peptides was reported to both increase and decrease antimicrobial activity. We used computer simulations and fluorescence experiments to show that a kink in helices affects the formation of membrane pores by stabilizing toroidal pores but disrupting barrel-stave pores. The position of the proline/glycine kink in the sequence further controls the specific structure of toroidal pore. Moreover, we demonstrate that two helical peptides can form a kink-like connection with similar behavior as one long helical peptide with a kink. The provided molecular-level insight can be utilized for design and modification of pore-forming antibacterial peptides or toxins. © 2020, Tuerkova et al.in English, French Title Brachylaima spp. (Trematoda) parasitant Cornu aspersum (Gastropoda) en France et risque potentiel pour la consommation humaine. Abstract L’escargot Cornu aspersum, originaire des côtes méditerranéennes d’Afrique du Nord, est largement répandu sur la plupart des continents et souvent invasif dans ses aires d’introduction récente. Cette espèce peut contribuer à l’expansion géographique de parasites comme démontré pour Brachylaima spp. Ces trématodes cosmopolites peuvent représenter une menace pour la santé comme en Australie où Brachylaima cribbi parasite l’espèce humaine. Dans cette étude, nous démontrons pour la première fois la présence de Brachylaima spp. dans deux populations françaises de C. aspersum, à Thorigné-Fouillard (Ille-et-Vilaine) et Arçais (Deux-Sèvres), avec une prévalence totale de 10.4 % (Thorigné-Fouillard) et 73.3 % (Arçais), et une intensité de métacercaires en moyenne trois fois plus importante à Thorigné-Fouillard (37) qu’à Arçais (11). Cornu aspersum peut jouer le rôle de premier et de second hôte intermédiaire, comme démontré à Arçais.