Enhancing preschoolers' executive functions through embedding cognitive activities in shared book reading

Given evidence that early executive functioning sets the stage for a broad range of subsequent outcomes, researchers have sought to identify ways to foster these cognitive capacities. An increasingly common approach involves computerized ‘brain training’ programs, yet there are questions about whether these are well suited for fostering the early development of executive functions (EFs). The current series of studies sought to design, develop, and provide evidence for the efficacy of embedding cognitive activities in a commonplace activity – shared reading of a children’s book. The book, Quincey Quokka’s Quest, required children to control their thinking and behaviour to help the story’s main character through a series of obstacles. The first study investigated effects of reading with embedded cognitive activities in individual and group contexts on young children’s executive functions (EFs). The second study compared reading with embedded cognitive activities against a more-active control condition (dialogic reading) that similarly engaged children in the reading process yet lacked clear engagement of EFs. The third study sought to investigate whether the effect of reading the story with embedded EF activities changed across differing doses of the intervention and whether effects persisted 2 months post-intervention. Findings provide converging evidence of intervention effects on working memory and shifting in as little as 3 weeks (compared to more traditional reading) and maintenance of these gains 2 months later. This suggests the efficacy of embedding cognitive activities in the context of everyday activities, thereby extending the range of users and contexts in which this approach can be used

Green Fabrication of Sulfonium Containing Bismuth Materials for High Sensitivity X Ray Detection

Organic inorganic hybrid materials based on lead and bismuth have recently been proposed as novel X and gamma ray detectors for medical imaging, non destructive testing, and security, due to their high atomic numbers and facile preparation compared to traditional materials like amorphous selenium and Cd Zn Te. However, challenges related to device operation, excessively high dark currents, and long term stability have delayed commercialization. Here, two novel semiconductors incorporating stable sulfonium cations are presented, [ CH3CH2 3S]6Bi8I30 and [ CH3CH2 3S]AgBiI5, synthesized via solvent free ball milling and fabricated into dense polycrystalline pellets using cold isostatic compression, two techniques that can easily be upscaled, for X ray detection application. The fabricated detectors exhibit exceptional sensitivities 14 100 15 190 C Gyair amp; 8722;1 cm amp; 8722;2 and low detection limits 90 nGyair s amp; 8722;1 for [ CH3CH2 3S]6Bi8I30 and 78 nGyair s amp; 8722;1 for [ CH3CH2 3S]AgBiI5 , far surpassing current commercial detectors. Notably, they maintain performance after 9 months of ambient storage. The findings highlight [ CH3CH2 3S]6Bi8I30 and [ CH3CH2 3S]AgBiI5 as scalable, cost effective and highly stable alternatives to traditional semiconductor materials, offering great potential as X ray detectors in medical and security application

Inhibition of MALT1 protease activity is selectively toxic for activated B cell-like diffuse large B cell lymphoma cells.

Diffuse large B cell lymphoma (DLBCL) is the most common type of lymphoma in humans. The aggressive activated B cell-like (ABC) subtype of DLBCL is characterized by constitutive NF-kappa B activity and requires signals from CARD11, BCL10, and the paracaspase MALT1 for survival. CARD11, BCL10, and MALT1 are scaffold proteins that normally associate upon antigen receptor ligation. Signal-induced CARD11-BCL10-MALT1 (CBM) complexes couple upstream events to I kappa B kinase (IKK)/NF-kappa B activation. MALT1 also possesses a recently recognized proteolytic activity that cleaves and inactivates the negative NF-kappa B regulator A20 and BCL10 upon antigen receptor ligation. Yet, the relevance of MALT1 proteolytic activity for malignant cell growth is unknown. Here, we demonstrate preassembled CBM complexes and constitutive proteolysis of the two known MALT1 substrates in ABC-DLBCL, but not in germinal center B cell-like (GCB) DLBCL. ABC-DLBCL cell treatment with a MALT1 protease inhibitor blocks A20 and BCL10 cleavage, reduces NF-kappa B activity, and decreases the expression of NF-kappa B targets genes. Finally, MALT1 paracaspase inhibition results in death and growth retardation selectively in ABC-DLBCL cells. Thus, our results indicate a growth-promoting role for MALT1 paracaspase activity in ABC-DLBCL and suggest that a pharmacological MALT1 protease inhibition could be a promising approach for lymphoma treatment

A20 negatively regulates T cell receptor signaling to NF-κB by cleaving Malt1 ubiquitin chains.

The Carmal-Bcl10-Malt1 signaling module bridges TCR signaling to the canonical I kappa B kinase (IKK)/NF-kappa B pathway. Covalent attachment of regulatory ubiquitin chains to Malt1 paracaspase directs TCR signaling to IKK activation. Further, the ubiquitin-editing enzyme A20 was recently suggested to suppress T cell activation, but molecular targets for A20 remain elusive. In this paper, we show that A20 regulates the strength and duration of the IKK/NF-kappa B response upon TCR/CD28 costimulation. By catalyzing the removal of K63-linked ubiquitin chains from Malt1, A20 prevents sustained interaction between ubiquitinated Malt1 and the IKK complex and thus serves as a negative regulator of inducible IKK activity. Upon T cell stimulation, A20 is rapidly removed and paracaspase activity of Malt1 has been suggested to cleave A20. Using antagonistic peptides or reconstitution of Malt1(-/-) T cells, we show that Malt1 paracaspase activity is required for A20 cleavage and optimal IL-2 production, but dispensable for initial IKK/NF-kappa B signaling in CD4(+) T cells. However, proteasomal inhibition impairs A20 degradation and impedes TCR/CD28-induced IKK activation. Taken together, A20 functions as a Malt1 deubiquitinating enzyme and proteasomal degradation and de novo synthesis of A20 contributes to balance TCR/CD28-induced IKK/NF-kappa B signaling

Role of oxidative stress in ultrafine particle-induced exacerbation of allergic lung inflammation.

Rationale: The effects of ultrafine particle inhalation on allergic airway inflammation are of growing interest. The mechanisms underlying these effects are currently under investigation. Objectives: To investigate the role of oxidative stress on the adjuvant activity of inhaled elemental carbon ultrafine particles (EC-UFPs) on allergic airway inflammation. Methods: Ovalbumin-sensitized mice were exposed to EC-UFPs (504 mu g/m(3) for 24 h) or filtered air immediately before allergen challenge and systemically treated with N-acetylcysteine or vehicle before and during EC-UFP inhalation. Allergic inflammation was measured up to 1 week after allergen challenge by means of bronchoalveolar lavage, cytokine/total protein assays, lung function, and histology. Isoprostane levels in lung tissue served to measure oxidative stress. Transmission electron microscopy served to localize ECUFPs in lung tissue and both electrophoretic mobility shift assay and immunohistochemistry to quantify/localize nuclear factor-kappa B (NF-kappa B) activation. Measurements and Main Results: In sensitized and challenged mice EC-UFP inhalation increased allergen-induced lung lipid peroxidation and NF-kappa B activation in addition to inflammatory infiltrate, cytokine release, and airway hyperresponsiveness. Prominent NF-kappa B activation was observed in the same cell types in which EC-UFPs were detected. N-acetylcysteine treatment significantly reduced the adjuvant activity of EC-UFPs. In nonsensitized or sensitized but not challenged mice EC-UFP exposure induced a moderate increase in isoprostanes but no significant effect on other parameters of lung inflammation. Conclusions: Our findings demonstrate a critical role for oxidative stress in EC-UFP-induced augmentation of allergen-induced lung inflammation, where EC-UFP exposure has potentiating effects in lung allergic inflammation. Our data support the concept that allergic individuals are more susceptible to the adverse health effects of EC-UFPs