Deferred imitation and declarative memory in domestic dogs

This study demonstrates for the first time deferred imitation of novel actions in dogs (Canis familiaris) with retention intervals of 1.5 min and memory of familiar actions with intervals ranging from 0.40 to 10 min. Eight dogs were trained using the 'Do as I do' method to match their own behaviour to actions displayed by a human demonstrator. They were then trained to wait for a short interval to elapse before they were allowed to show the previously demonstrated action. The dogs were then tested for memory of the demonstrated behaviour in various conditions, also with the so-called two-action procedure and in a control condition without demonstration. Dogs were typically able to reproduce familiar actions after intervals as long as 10 min, even if distracted by different activities during the retention interval and were able to match their behaviour to the demonstration of a novel action after a delay of 1 min. In the two-action procedure, dogs were typically able to imitate the novel demonstrated behaviour after retention intervals of 1.5 min. The ability to encode and recall an action after a delay implies that facilitative processes cannot exhaustively explain the observed behavioural similarity and that dogs' imitative abilities are rather based on an enduring mental representation of the demonstration. Furthermore, the ability to imitate a novel action after a delay without previous practice suggests presence of declarative memory in dogs. © 2013 Springer-Verlag Berlin Heidelberg

Bone marrow niche trafficking of miR-126 controls the self-renewal of leukemia stem cells in chronic myelogenous leukemia

Leukemia stem cells (LSCs) in individuals with chronic myelogenous leukemia (CML) (hereafter referred to as CML LSCs) are responsible for initiating and maintaining clonal hematopoiesis. These cells persist in the bone marrow (BM) despite effective inhibition of BCR–ABL kinase activity by tyrosine kinase inhibitors (TKIs). Here we show that although the microRNA (miRNA) miR-126 supported the quiescence, self-renewal and engraftment capacity of CML LSCs, miR-126 levels were lower in CML LSCs than in long-term hematopoietic stem cells (LT-HSCs) from healthy individuals. Downregulation of miR-126 levels in CML LSCs was due to phosphorylation of Sprouty-related EVH1-domain-containing 1 (SPRED1) by BCR–ABL, which led to inhibition of the RAN–exportin-5–RCC1 complex that mediates miRNA maturation. Endothelial cells (ECs) in the BM supply miR-126 to CML LSCs to support quiescence and leukemia growth, as shown using mouse models of CML in which Mir126a (encoding miR-126) was conditionally knocked out in ECs and/or LSCs. Inhibition of BCR–ABL by TKI treatment caused an undesired increase in endogenous miR-126 levels, which enhanced LSC quiescence and persistence. Mir126a knockout in LSCs and/or ECs, or treatment with a miR-126 inhibitor that targets miR-126 expression in both LSCs and ECs, enhanced the in vivo anti-leukemic effects of TKI treatment and strongly diminished LSC leukemia-initiating capacity, providing a new strategy for the elimination of LSCs in individuals with CML

Unraveling sources of stimulus control in a temporal discrimination task

In temporal discriminations tasks, more than one stimulus may function as a time marker. We studied two of them in a matching-to-sample task, the sample keylight and the houselight that signaled the intertrial interval (ITI). One group of pigeons learned a symmetrical matching-to-sample task with two samples (2 s or 18 s of a center keylight) and two comparisons (red and green side keys), whereas another group of pigeons learned an asymmetrical matching-to-sample task with three samples (2 s, 6 s, and 18 s) and two comparisons (red and green). In the asymmetrical task, 6-s and 18-s samples shared the same comparison. In a subsequent retention test, both groups showed a preference for the comparison associated with the longer samples, a result consistent with the hypothesis that pigeons based their choices on the duration elapsed since the offset of the houselight (i.e., sample duration + retention interval). Results from two no-sample tests further corroborated the importance of the ITI illumination as a time marker: When the ITI was illuminated, the proportion of choices correlated positively with the retention interval; when the ITI was darkened, choices fell to random levels. However, the absolute value of choice proportions suggested that the sample stimulus was also a time marker. How multiple stimuli acquire control over behavior and how they combine remains to be worked out.This work was conducted at the Psychology Research Centre, University of Minho, and was supported by the Portuguese Foundation for Science and Technology (FCT) and the Portuguese Ministry of Education and Science through national funds, and when applicable co-financed by FEDER under the PT2020 Partnership Agreement (UID/PSI/01662/2013). This work was also supported by a FCT Doctoral Grant (SFRH/BD/78566/2011) to Carlos Pinto and a FCT Grant (PTDC/MHC-PCN/3540/2012) to Armando Machado.info:eu-repo/semantics/publishedVersio