RelB contributes to the survival, migration and lymphomagenesis of B cells with constitutively active CD40 signaling.

Activation of CD40-signaling contributes to the initiation, progression and drug resistance of B cell lymphomas. We contributed to this knowledge by showing that constitutive CD40-signaling in B cells induces B cell hyperplasia and finally B cell lymphoma development in transgenic mice. CD40 activates, among others, the non-canonical NF-ĸB signaling, which is constitutively activated in several human B cell lymphomas and is therefore presumed to contribute to lymphopathogenesis. This prompted us to study the regulatory role of the non-canonical NF-ĸB transcription factor RelB in lymphomagenesis. To this end, we crossed mice expressing a constitutively active CD40 receptor in B cells with conditional RelB-KO mice. Ablation of RelB attenuated pre-malignant B cell expansion, and resulted in an impaired survival and activation of long-term CD40-stimulated B cells. Furthermore, we found that hyperactivation of non-canonical NF-кB signaling enhances the retention of B cells in the follicles of secondary lymphoid organs. RNA-Seq-analysis revealed that several genes involved in B-cell migration, survival, proliferation and cytokine signaling govern the transcriptional differences modulated by the ablation of RelB in long-term CD40-stimulated B cells. Inactivation of RelB did not abrogate lymphoma development. However, lymphomas occurred with a lower incidence and had a longer latency period. In summary, our data suggest that RelB, although it is not strictly required for malignant transformation, accelerates the lymphomagenesis of long-term CD40-stimulated B cells by regulating genes involved in migration, survival and cytokine signaling.

Incorporating callous-unemotional behaviors into school-based research.

This study investigated the utility of including teacher-reported callous-unemotional (CU) behaviors in the assessment of disruptive behaviors in school-based research. Participants included 138 first- and second-grade children (68% male; 76% eligible for free or reduced-price lunch; 61% Black, 9% Latinx, 23% White, and 7% multiracial) who completed assessments during the baseline assessment of an intervention study. Results indicated that teachers could distinguish CU from traditional indicators of disruptive behavior, including attention deficit hyperactivity disorder (ADHD) behaviors and conduct problems (CP). When considered alone, there was mixed evidence for the utility of CU behaviors. Although higher levels of CU behaviors explained unique variation in teacher-reported social competence and global impairment, CU behaviors did not explain unique variation in disciplinary infractions, classroom behavior, or academic functioning after accounting for ADHD and CP behaviors. A different pattern of results was evident when CU was considered in conjunction with ADHD and CP behaviors. Latent profile analyses identified three subgroups of participants (i.e., a nondisruptive group, an ADHD group, and a comorbid group, who exhibited elevated levels of ADHD, CP, and CU). Compared to the nondisruptive group, the ADHD group exhibited higher rates of off-task classroom behavior and worse academic functioning. The comorbid group exhibited moderate-to-large differences from both groups on teacher-reported and objective outcomes. The implications of these results are discussed with respect to the potential value of incorporating CU behaviors, which are becoming prominent in clinical psychology and psychiatry, into school-based research and for school psychology practice. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

ERK phosphorylation is RAF independent in naïve and activated B cells but RAF dependent in plasma cell differentiation.

Members of the RAF family of serine-threonine kinases are intermediates in the mitogen-activated protein kinase and extracellular signal-regulated kinase (MAPK-ERK) signaling pathway, which controls key differentiation processes in B cells. By analyzing mice with B cell-specific deletion of Raf1, Braf, or both, we showed that Raf-1 and B-Raf acted together in mediating the positive selection of pre-B and transitional B cells as well as in initiating plasma cell differentiation. However, genetic or chemical inactivation of RAFs led to increased ERK phosphorylation in mature B cells. ERK activation in the absence of Raf-1 and B-Raf was mediated by multiple RAF-independent pathways, with phosphoinositide 3-kinase (PI3K) playing an important role. Furthermore, we found that ERK phosphorylation strongly increased during the transition from activated B cells to pre-plasmablasts. This increase in ERK phosphorylation did not occur in B cells lacking both Raf-1 and B-Raf, which most likely explains the partial block of plasma cell differentiation in mice lacking both RAFs. Collectively, our data indicate that B-Raf and Raf-1 are not necessary to mediate ERK phosphorylation in naïve or activated B cells but are essential for mediating the marked increase in ERK phosphorylation during the transition from activated B cells to pre-plasmablasts.

The Educare intervention: Outcomes at age 3.

The effectiveness of Educare, a center-based early education program, in improving child outcomes at age 3 was evaluated in a randomized clinical trial. Educare programs serve children from birth to age 5 and are designed to reduce the achievement gap between children from low-income families and their more advantaged peers. This study began following 239 children from low-income families who were randomly assigned as infants (<19 months) to Educare or a business-as-usual control group. At age 3, assessments of the skills of 202 children remaining in the study revealed significant differences in favor of children in the treatment group on auditory language skills, early math skills, and parent-reported problem behaviors. Effect sizes were in the modest range, although not as strong as the previously reported age 2 findings. No effects were found for observations of parent-child interactions, observer-rated child behaviors, or parent-rated social competence. For English-language skills, children who were dual language learners (DLLs) benefitted more from treatment than non-DLLs. Analyses of outcomes by child care type, regardless of treatment group assignment, showed that children in Educare had better language, math, and behavioral scores than children in less formal care, whereas children in other center-based care only had higher language scores than children in less formal care. Differences in outcomes between Educare and other center-based care were not significant.

PiggyBac transposon tools for recessive screening identify B-cell lymphoma drivers in mice.

B-cell lymphoma (BCL) is the most common hematologic malignancy. While sequencing studies gave insights into BCL genetics, identification of non-mutated cancer genes remains challenging. Here, we describe PiggyBac transposon tools and mouse models for recessive screening and show their application to study clonal B-cell lymphomagenesis. In a genome-wide screen, we discover BCL genes related to diverse molecular processes, including signaling, transcriptional regulation, chromatin regulation, or RNA metabolism. Cross-species analyses show the efficiency of the screen to pinpoint human cancer drivers altered by non-genetic mechanisms, including clinically relevant genes dysregulated epigenetically, transcriptionally, or post-transcriptionally in human BCL. We also describe a CRISPR/Cas9-based in vivo platform for BCL functional genomics, and validate discovered genes, such as Rfx7, a transcription factor, and Phip, a chromatin regulator, which suppress lymphomagenesis in mice. Our study gives comprehensive insights into the molecular landscapes of BCL and underlines the power of genome-scale screening to inform biology.

Integrating Item Accuracy and Reaction Time to Improve the Measurement of Inhibitory Control Abilities in Early Childhood.

Efforts to improve children's executive function are often hampered by the lack of measures that are optimized for use during the transition from preschool to elementary school. Whereas preschool-based measures often emphasize response accuracy, elementary school-based measures emphasize reaction time (RT)-especially for measures inhibitory control (IC) tasks that typically have a speeded component. The primary objective of this study was to test in a preschool-aged sample whether the joint use of item-level accuracy and RT data resulted in improved scoring for three IC tasks relative to scores derived from accuracy data alone. Generally, the joint use of item-level accuracy and RT data resulted in modest improvements in the measurement precision of IC abilities. Moreover, the joint use of item-level accuracy and RT helped eliminate floor and ceiling effects that occurred when accuracy data were considered alone. Results are discussed with respect to the importance of scoring IC tasks in ways that are maximally informative for program evaluation and longitudinal modeling.

Maternal Language and Child Vocabulary Mediate Relations Between Socioeconomic Status and Executive Function During Early Childhood.

This article examined longitudinal relations among socioeconomic risk, maternal language input, child vocabulary, and child executive function (EF) in a large sample (N = 1,009) recruited for a prospective longitudinal study. Two measures of maternal language input derived from a parent-child picture book task, vocabulary diversity (VOCD), and language complexity, showed variation by socioeconomic risk at child ages 15, 24, and 36 months. Maternal VOCD at child age 24 months and maternal language complexity at child age 36 months mediated the relation between socioeconomic risk and 48-month child EF, independent of parenting sensitivity. Moreover, 36-month child vocabulary mediated the relation between maternal language input and child EF. These findings provide novel evidence about mechanisms linking socioeconomic risk and child executive function.

Surface distortion as a unifying concept and descriptor in oxygen reduction reaction electrocatalysis.

Tuning the surface structure at the atomic level is of primary importance to simultaneously meet the electrocatalytic performance and stability criteria required for the development of low-temperature proton-exchange membrane fuel cells (PEMFCs). However, transposing the knowledge acquired on extended, model surfaces to practical nanomaterials remains highly challenging. Here, we propose 'surface distortion' as a novel structural descriptor, which is able to reconciliate and unify seemingly opposing notions and contradictory experimental observations in regards to the electrocatalytic oxygen reduction reaction (ORR) reactivity. Beyond its unifying character, we show that surface distortion is pivotal to rationalize the electrocatalytic properties of state-of-the-art of PtNi/C nanocatalysts with distinct atomic composition, size, shape and degree of surface defectiveness under a simulated PEMFC cathode environment. Our study brings fundamental and practical insights into the role of surface defects in electrocatalysis and highlights strategies to design more durable ORR nanocatalysts.

Investigating teacher and student effects of the Incredible Years Classroom Management Program in early elementary school.

The present paper reports on the results of a cluster randomized trial of the Incredible Years® Teacher Classroom Management Program (IY-TCM) and its effects on early elementary teachers' management strategies, classroom climate, and students' emotion regulation, attention, and academic competence. IY-TCM was implemented in 11 rural and semi-rural schools with K-2 teachers and a diverse student sample. Outcomes were compared for 45 teachers who participated in five full day training workshops and brief classroom consultation and 46 control teachers; these 91 teachers had a total of 1192 students. A high level of teacher satisfaction was found and specific aspects of the training considered most valuable for early elementary teachers were identified. Hierarchical linear modeling indicated a statistically significant intervention effect on Positive Climate in the classroom (d=0.45) that did not sustain into the next school year. No main effects on student outcomes were observed, although a priori moderator analyses indicated that students with elevated social-behavioral difficulties benefitted with regard to prosocial behavior (d=0.54) and inattention (d=-0.34). Results highlight potential benefits and limitations of a universal teacher training program for elementary students, and suggest strategies for future delivery of the IY-TCM program and areas for future research.

The benefits of adding a brief measure of simple reaction time to the assessment of executive function skills in early childhood.

Early childhood represents a period of rapid cognitive developmental change in executive function (EF) skills along with a variety of related cognitive processes, including processing speed. This leads to interpretational challenges in that children's performance on EF tasks reflects more than EF skills per se. We tested whether the inclusion of a brief measure of simple reaction time (SRT) during EF assessments could help to partially address this challenge. Data were drawn from a cross-sectional convenience sample of 830 preschool-aged children. Individual differences in SRT were significantly associated with performance on all tasks (R2s = .09-.26); slower performance on the SRT task was associated with poorer performance on each EF task. Age-related differences in individual EF tasks were reduced by approximately one half after accounting for age-related differences in SRT, and EF task scores were less coherent (i.e., less strongly intercorrelated with each other) after the removal of SRT. Age-related differences in EF were smaller (Cohen ds = 1.36 vs. 0.78), and poverty-related differences in EF were larger (Cohen ds = 0.30 vs. 0.46) after accounting for SRT-related variation. Finally, consistent with previous studies, SRT-related differences in fluid reasoning were mediated by EF skills. Results are discussed with respect to using a brief measure of SRT to partially address the problem of measurement impurity at the level of individual EF tasks.

The Childhood Executive Functioning Inventory (CHEXI): Factor structure, measurement invariance, and correlates in US preschoolers.

This study tests the factor structure, measurement invariance, and correlates of the Childhood Executive Functioning Inventory (CHEXI) with a large and diverse sample of 3- to 5-year-olds (n = 844). Consistent with previous studies, a two-factor model that distinguishes working memory from inhibition provides the best fit to the observed data. This two-factor model has been shown to demonstrate strong measurement invariance for different subgroups of children (boys vs. girls, high vs. low income). Whereas boys tend to have greater working memory and inhibition difficulties (Cohen's d = 0.15 and 0.20, respectively), children from low-income households tend to have more working memory problems than their peers from high-income households (Cohen's d = 0.25). Finally, correlations between CHEXI scores, examiner reports of child behavior, and child performance on a battery of executive function (EF) tasks were investigated. CHEXI scores were found to be more consistently related to examiner reports of child behavior than child performance on EF tasks. Tthe strengths and weaknesses of the CHEXI as a questionnaire measure of EF are discussed, and directions for future research are suggested.

Unsupported Pt-Ni Aerogels with Enhanced High Current Performance and Durability in Fuel Cell Cathodes.

Highly active and durable oxygen reduction catalysts are needed to reduce the costs and enhance the service life of polymer electrolyte fuel cells (PEFCs). This can be accomplished by alloying Pt with a transition metal (for example Ni) and by eliminating the corrodible, carbon-based catalyst support. However, materials combining both approaches have seldom been implemented in PEFC cathodes. In this work, an unsupported Pt-Ni alloy nanochain ensemble (aerogel) demonstrates high current PEFC performance commensurate with that of a carbon-supported benchmark (Pt/C) following optimization of the aerogel's catalyst layer (CL) structure. The latter is accomplished using a soluble filler to shift the CL's pore size distribution towards larger pores which improves reactant and product transport. Chiefly, the optimized PEFC aerogel cathodes display a circa 2.5-fold larger surface-specific ORR activity than Pt/C and maintain 90 % of the initial activity after an accelerated stress test (vs. 40 % for Pt/C).

Examining an Executive Function Battery for Use with Preschool Children with Disabilities.

Performance-based assessments of EF for use with young children who have or are at risk for disabilities are lacking. The current study investigates the use of a computerized battery for children with subclinical behaviors (N = 846) across a variety of developmental disabilities and evaluates practical information about feasibility of task administration. Results reveal that children with disabilities performed similarly to their typically developing peers across a variety of metrics for evaluating the battery, ranging from percent correct scores to administrator quality ratings. Thus, the battery may be considered an easy-to-administer, performance-based assessment tool in which children with disabilities do not perform systemically worse than typically developing peers.

The test-retest reliability of the latent construct of executive function depends on whether tasks are represented as formative or reflective indicators.

This study investigates the test-retest reliability of a battery of executive function (EF) tasks with a specific interest in testing whether the method that is used to create a battery-wide score would result in differences in the apparent test-retest reliability of children's performance. A total of 188 4-year-olds completed a battery of computerized EF tasks twice across a period of approximately two weeks. Two different approaches were used to create a score that indexed children's overall performance on the battery-i.e., (1) the mean score of all completed tasks and (2) a factor score estimate which used confirmatory factor analysis (CFA). Pearson and intra-class correlations were used to investigate the test-retest reliability of individual EF tasks, as well as an overall battery score. Consistent with previous studies, the test-retest reliability of individual tasks was modest (rs ≈ .60). The test-retest reliability of the overall battery scores differed depending on the scoring approach (rmean = .72; rfactor_score = .99). It is concluded that the children's performance on individual EF tasks exhibit modest levels of test-retest reliability. This underscores the importance of administering multiple tasks and aggregating performance across these tasks in order to improve precision of measurement. However, the specific strategy that is used has a large impact on the apparent test-retest reliability of the overall score. These results replicate our earlier findings and provide additional cautionary evidence against the routine use of factor analytic approaches for representing individual performance across a battery of EF tasks.

Alloying Behavior of Self-Assembled Noble Metal Nanoparticles.

The atomic redistribution processes occurring in multiparticle nanostructures are hardly understood. To obtain a more detailed insight, we applied high-resolution microscopic, diffraction and spectroscopic characterization techniques to investigate the fine structure and elemental distribution of various bimetallic aerogels with 1:1 compositions, prepared by self-assembly of single monometallic nanoparticles. The system Au-Ag exhibited a complete alloy formation, whereas Pt-Pd aerogels formed a Pd-based network with embedded Pt particles. The assembly of Au and Pd nanoparticles resulted in a Pd-shell formation around the Au particles. This work confirms that bimetallic aerogels are subject to reorganization processes during their gel formation.

The contribution of children's time-specific and longitudinal expressive language skills on developmental trajectories of executive function.

To investigate whether children's early language skills support the development of executive functions (EFs), the current study used an epidemiological sample (N=1121) to determine whether two key language indicators, vocabulary and language complexity, were predictive of EF abilities over the preschool years. We examined vocabulary and language complexity both as time-varying covariates that predicted time-specific indicators of EF at 36 and 60 months of age and as time-invariant covariates that predicted children's EF at 60 months and change in EF from 36 to 60 months. We found that the rate of change in children's vocabulary between 15 and 36 months was associated with both the trajectory of EF from 36 to 60 months and the resulting abilities at 60 months. In contrast, children's language complexity had a time-specific association with EF only at 60 months. These findings suggest that children's early gains in vocabulary may be particularly relevant for emerging EF abilities.

Interrelation Between Oxidative Stress and Complement Activation in Models of Age-Related Macular Degeneration.

Millions of individuals older than 50-years suffer from age-related macular degeneration (AMD). Associated with this multifactorial disease are polymorphisms of complement factor genes and a main environmental risk factor-oxidative stress. Until now the linkage between these risk factors for AMD has not been fully understood. Recent studies, integrating results on oxidative stress, complement activation, epidemiology and ocular pathology suggested the following sequence in AMD-etiology: initially, chronic oxidative stress results in modification of proteins and lipids in the posterior of the eye; these tissue alterations trigger chronic inflammation, involving the complement system; and finally, invasive immune cells facilitate pathology in the retina. Here, we summarize the results for animal studies which aim to elucidate this molecular interplay of oxidative events and tissue-specific complement activation in the eye.

Early communicative gestures prospectively predict language development and executive function in early childhood.

Using an epidemiological sample (N = 1,117) and a prospective longitudinal design, this study tested the direct and indirect effects of preverbal and verbal communication (15 months to 3 years) on executive function (EF) at age 4 years. Results indicated that whereas gestures (15 months), as well as language (2 and 3 years), were correlated with later EF (φs ≥ .44), the effect was entirely mediated through later language. In contrast, language had significant direct and indirect effects on later EF. Exploratory analyses indicated that the pattern of results was comparable for low- and not-low-income families. The results were consistent with theoretical accounts of language as a precursor of EF ability, and highlighted gesture as an early indicator of EF.

On the Validity of the Rapid Estimate of Adult Literacy in Medicine (REALM) Scale as a Measure of Health Literacy.

Originally developed to measure the literacy level of patients, the Rapid Estimate of Adult Literacy in Medicine (REALM) scale is one of the most widely used instruments to measure the construct of health literacy. This article critically examines the validity of the REALM as a measure of health literacy. Logical analysis of content coverage led to the conclusion that scores on the REALM should not be used to make inferences about a person's level of health literacy. Rather, the REALM should be used to make inferences about the ability of a person to read and pronounce health related terms. Evidence from an analysis of a sample of 1,037 respondents to the REALM with a cancer diagnosis supports the quality of the REALM as a measure of reading and pronunciation ability. Other uses of the REALM in health literacy research are discussed.

Cancer patients' information needs the first nine months after diagnosis.

OBJECTIVE: Cancer patients' information needs about disease, diagnostic tests, treatments, physical care, and psychosocial resources during treatment are examined. METHODS: Information needs of newly diagnosed, Stages II-IV cancer patients receiving treatment (N=138) were studied over nine months. Information needs were assessed using The Toronto Informational Needs Questionnaire (TINQ). There are five subscales for the TINQ: disease, diagnostic tests, treatment, physical and psychosocial. Health literacy and amount of information wanted were also measured. A repeated measures, univariate two-level model for longitudinal data was analyzed. Separate models for each subscale were constructed and covariates were examined simultaneously for associations with information needs. Models were estimated using FIML. RESULTS: Although significant reduction of needs was observed over time, total information needs remained high throughout. Gender (women), age (younger), race (African American), education (lesser), and marital status (married) were significantly associated with higher information needs over time. Cancer type and stage were not significantly associated. CONCLUSION: Cancer patients' information needs decrease yet remain high over time. Patients' information needs are highest near diagnosis and change throughout the course of their treatment. PRACTICE IMPLICATIONS: As patients obtain and understand information, they will continue to need information in new areas relevant to their care.