This experimental research assessed the influence of graded levels of self‐distancing – psychological distancing from one's egocentric perspective – on executive function (EF) in young children. ...Three‐ (n = 48) and 5‐year‐old (n = 48) children were randomly assigned to one of four manipulations of distance from the self (from proximal to distal: self‐immersed, control, third person, and exemplar) on a comprehensive measure of EF. Performance increased as a function of self‐distancing across age groups. Follow‐up analyses indicated that 5‐year‐olds were driving this effect. They showed significant improvements in EF with increased distance from the self, outperforming controls both when taking a third person perspective on the self and when taking the perspective of an exemplar other (e.g., Batman) through role play. Three‐year‐olds, however, did not show increased EF performance as a function of greater distance from the self. Preliminary results suggest that developments in theory of mind might contribute to these age‐related differences in efficacy. These findings speak to the importance of psychological distancing in the expression of conscious control over thought and action from a young age and suggest a promising new avenue for early EF intervention.
Self‐distancing (by taking a third person perspective on the self or taking the perspective of an exemplar other) improved executive function in 5‐year‐olds, but not 3‐year‐olds. Preliminary evidence suggests that these age‐related differences could be attributable, at least in part, to improvements in theory of mind.
Transmembrane member 16A (TMEM16A) is a widely expressed Ca2+-activated Cl− channel with various physiological functions ranging from mucosal secretion to regulating smooth muscle contraction. ...Understanding how TMEM16A controls these physiological processes and how its dysregulation may cause disease requires a detailed understanding of how cellular processes and second messengers alter TMEM16A channel gating. Here we assessed the regulation of TMEM16A gating by recording Ca2+-evoked Cl− currents conducted by endogenous TMEM16A channels expressed in Xenopus laevis oocytes, using the inside-out configuration of the patch clamp technique. During continuous application of Ca2+, we found that TMEM16A-conducted currents decay shortly after patch excision. Such current rundown is common among channels regulated by phosphatidylinositol 4,5-bisphosphate (PIP2). Thus, we sought to investigate a possible role of PIP2 in TMEM16A gating. Consistently, synthetic PIP2 rescued the current after rundown, and the application of PIP2 modulating agents altered the speed kinetics of TMEM16A current rundown. First, two PIP2 sequestering agents, neomycin and anti-PIP2, applied to the intracellular surface of excised patches sped up TMEM16A current rundown to nearly twice as fast. Conversely, rephosphorylation of phosphatidylinositol (PI) derivatives into PIP2 using Mg-ATP or inhibiting dephosphorylation of PIP2 using β-glycerophosphate slowed rundown by nearly 3-fold. Our results reveal that TMEM16A regulation is more complicated than it initially appeared; not only is Ca2+ necessary to signal TMEM16a opening, but PIP2 is also required. These findings improve our understanding of how the dysregulation of these pathways may lead to disease and suggest that targeting these pathways could have utility for potential therapies.
This study investigated the benefits of self-distancing (i.e., taking an outsider's view of one's own situation) on young children's perseverance. Four- and 6-year-old children (N = 180) were asked ...to complete a repetitive task for 10 min while having the option to take breaks by playing an extremely attractive video game. Six-year-olds persevered longer than 4-year-olds. Nonetheless, across both ages, children who impersonated an exemplar other—in this case a character, such as Batman—spent the most time working, followed by children who took a third-person perspective on the self, or finally, a first-person perspective. Alternative explanations, implications, and future research directions are discussed.
•3-year-old children heard realistic or fantastical stories.•They were encouraged to engage in story-based pretend play or a control activity.•Children in the pretense group exhibited increased ...inhibitory control.•Story content (realistic or fantastical) did not affect inhibitory control.
Fictional stories can affect many aspects of children’s behavior and cognition, yet little is known about how they might help or hinder children’s executive function skills. The current study investigated the role of story content (fantasy or reality) and mode of engagement with the story (pretense or a non-pretense control) on children’s inhibitory control, an important component of early executive function. A total of 60 3-year-olds were randomly assigned to hear a fantastical or realistic story and were encouraged to engage in either pretense or a non-pretense activity related to the story. They then completed the Less Is More task of inhibitory control. Story content had no impact on children’s inhibitory control; children performed equally well after hearing a fantastical or realistic story. However, children who engaged in story-related pretend play showed greater inhibitory control than those who engaged in a non-pretense activity. We found no interaction between story content and play engagement type. These results held when controlling for baseline inhibitory control, receptive vocabulary, age, gender, affect, and propensity toward pretense. Therefore, mode of play engagement with a story was more important in promoting children’s inhibitory control skills than the degree of realism in the story.
Amyloid plaques and neurofibrillary tangles co-occur in Alzheimer disease, but with different topological and temporal patterns. Whether these two lesions are independent or pathobiologically related ...is uncertain. For example, amyloid deposition in the neocortex precedes the spread of tau neurofibrillary tangles from the limbic areas to the cortex. We examined the aggregation properties of tau isolated from human cases with early tau pathology (Braak II) with and without plaques. Using a well-established HEK cell biosensor assay, we show that tau from cases with plaques has an enhanced ability to induce tau aggregates compared to tau from cases without plaques. To further explore this effect, we combined mice carrying the APP/PS1 transgene array that develop plaques with rTg4510 mice carrying the P301L mutant human tau transgene that develop extensive tau pathology with age. The resulting APP/PS1-rTg4510 mice had a threefold increase in tau seeding activity over the rTg4510 strain, without change in tau production or extracellular release. Surprisingly, this effect was observed before overt amyloid deposition. The enhancement of tau aggregation was also apparent by an increase in histological measures of tau pathology in young APP/PS1-rTg4510 mice and an increase in high-molecular-weight tau. Overall, these data provide evidence that amyloid β acts to enhance tau pathology by increasing the formation of tau species capable of seeding new aggregates.
Abstract In the present report we aimed to analyze the incremental value of preoperative magnetic resonance imaging (MRI), in addition to clinical variables and clinically-derived nomograms, in ...predicting outcomes radical prostatectomy (RP). All Mayo Clinic RP patients who underwent preoperative 1.5-Tesla MRI with endo-rectal coil from 2003 to 2013 were identified. Clinical and histopathological variables were used to calculate Partin estimates and Cancer of the Prostate Risk Assessment (CAPRA) score. MRI results in terms of extracapsular extension (ECE), seminal vesicle invasion (SVI), and lymph-node invasion (N+) were recorded. Using RP pathology as gold standard, we developed multivariate logistic regression models based on clinical variables, Partin Tables, and CAPRA score, and assessed their predictive accuracy before and after the addition of MRI results. Five hundred and one patients were included. MRI + clinical models outperformed clinical-based models alone for all outcomes. Comparing Partin and Partin + MRI predictive models, the areas under the curve were 0.61 versus 0.73 for ECE, 0.75 versus 0.82 for SVI, and 0.82 versus 0.85 for N+. Comparing CAPRA and CAPRA + MRI models, the areas under the curve were 0.69 versus 0.77 for ECE, 0.75 versus 0.83 for SVI, and 0.82 versus 0.85 for N+. Our data show that MRI can improve clinical-based models in prediction of nonorgan confined disease, particularly for ECE and SVI. Patient summary Magnetic resonance imaging, together with clinical information, can be useful in preoperative assessment before radical prostatectomy.
•A developmental relation between executive function (EF) and pretense is investigated in the preschool period.•A large battery of EF measures fit both a 1-factor and a 2-factor (Conflict and Delay) ...model in a confirmatory factor analysis.•Individual differences in pretense representation and EF were significantly related, over and above several controls.•Understanding the pretend–reality distinction was related to Conflict EF, whereas performing pretend actions was related to Delay EF.•A bidirectional between EF and pretense is proposed, with implications for pretend play interventions designed to foster EF development.
Several theoretical formulations suggest a relation between children's pretense and executive function (EF) skills. However, there is little empirical evidence for a correlation between these constructs in early development. Preschool children (N=104; M age=4–0) were given batteries of EF and pretense representation measures, as well as verbal, memory, and appearance-reality control tasks. Confirmatory factor analysis revealed two separable but overlapping aspects of EF (Conflict and Delay). EF was significantly related to pretense after accounting for all controls. Understanding the pretend–reality distinction was strongly related to Conflict EF, whereas performing pretend actions was more strongly related to Delay EF. These results, although correlational, are consistent with the claim that EF skills are implicated in pretense, such as inhibiting reality and flexibly manipulating dual representations, and offer a potential mechanism by which pretend play interventions may enhance childhood EF.
The Ca2+-conducting ion channel, CatSper, is expressed exclusively on the sperm flagellum and regulates sperm motility. A new study (Hwang et al., Cell, 2019) reveals that the pH-sensing and ...Ca2+-binding protein, EFCAB9, is a subunit of the CatSper channel and has a key role in triggering mammalian sperm to change their swimming at fertilization.
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