Gene–Environment Interactions and Intermediate Phenotypes: Early Trauma and Depression

This review focuses on current research developments in the study of gene by early life stress (ELS) interactions and depression. ELS refers to aversive experiences during childhood and adolescence such as sexual, physical or emotional abuse, emotional or physical neglect as well as parental loss. Previous research has focused on investigating and characterizing the specific role of ELS within the pathogenesis of depression and linking these findings to neurobiological changes of the brain, especially the stress response system. The latest findings highlight the role of genetic factors that increase vulnerability or, likewise, promote resilience to depression after childhood trauma. Considering intermediate phenotypes has further increased our understanding of the complex relationship between early trauma and depression. Recent findings with regard to epigenetic changes resulting from adverse environmental events during childhood promote current endeavors to identify specific target areas for prevention and treatment schemes regarding the long-term impact of ELS. Taken together, the latest research findings have underscored the essential role of genotypes and epigenetic processes within the development of depression after childhood trauma, thereby building the basis for future research and clinical interventions

Project NUMTEST: Assessing basic number competence without language

Although numerical skills are essential in modern societies, 5- 7 % of the population suffer from mathematical learning disabilities. Due to the hierarchical nature of mathematical knowledge, screening during the earliest stages of learning is essential to intervene efficiently. While different screening tools exist, they rely on verbal instructions and task content, hampering their usefulness in linguistically heterogeneous young school populations. We developed a computerized task that requires subjects to encode both auditory and visual numerical information to successfully respond to the task’s demands. For task instruction, participants were presented a video showing a person correctly solving three easy items of the task, before moving on to a practice session of three different items. If any item was solved incorrectly, the entire practice session was repeated for the participant. We administered the task to a sample of first grade students and collected participant’s performance in standardized addition, subtraction and number comparison (1 & 2-digit) tasks. A multivariate analysis with practice repetition as between-subject factor on the four standardized control measures revealed that participants that repeated the practice session scored significantly lower in three out of four dependent measures. These results suggest that the immediate understanding (i.e. practice items solved correctly on the first try) of our task, requiring deductive reasoning and an abstract, format-independent representation of quantity, is able to differentiate between high and low performers on standardized measures of basic math competence non-verbally at an early stage of learning. Implications and limitations will be discussed

Project NUMTEST: Assessing basic number competence without language

While numerical skills are fundamental in modern societies, some estimated 5-7% of children suffer from a mathematical learning disorder, called developmental dyscalculia (DD). Nevertheless, universally valid diagnostic instruments are still lacking, as all current DD test batteries are based on language instructions. Consequently, their measurements are tightly linked to the specific language context of test administration and thus their results cannot easily be compared across countries. Here we are showing results of the first pilot study of a research project that aims to develop a test for basic math abilities that does not rely on language instruction and minimizes language use. To this aim, video and animation based instructions were implemented on touchscreen devices. A first version of the tasks has been tested with two samples of first grade children in Luxembourg’s fundamental schools, of which half completed the same tasks with traditional verbal instructions. Our results indicate that performance in the experimental group was similar or better than the control group using verbal instructions. Relationships between linguistic background and the sample’s performance on one hand and qualitative usability aspects of nonverbal task instruction and tablet-pc use with young children will be discussed

Predicting first-grade mathematics achievement: the contributions of domain-general cognitive abilities, nonverbal number sense, and early number competence

Early number competence, grounded in number-specific and domain-general abilities, is supposed to lay the foundation for later math achievement. Few longitudinal studies tested a comprehensive model for early math development. Using structural equation modeling and mediation analyses, we studied the influence of kindergarteners’ basic cognitive abilities (i.e., nonverbal number sense, working memory, fluid intelligence, and receptive vocabulary) and their early number competence (i.e., symbolic number skills) on first grade math achievement (arithmetic, shape and space, and number line estimation) assessed one year later. Latent regression models revealed that nonverbal number sense and working memory are central building blocks for developing early number competence in kindergarten and that early number competence is key for first grade math achievement. Fluid intelligence significantly predicted arithmetic and number line estimation while receptive vocabulary significantly predicted shape and space after controlling for early number competence. In sum we suggest that early math achievement draws on different constellations of number-specific and domain-general mechanisms

Taking Language out of the Equation: The Assessment of Basic Math Competence Without Language

While numerical skills are fundamental in modern societies, some estimated 5–7% of children suffer from mathematical learning difficulties (MLD) that need to be assessed early to ensure successful remediation. Universally employable diagnostic tools are yet lacking, as current test batteries for basic mathematics assessment are based on verbal instructions. However, prior research has shown that performance in mathematics assessment is often dependent on the testee's proficiency in the language of instruction which might lead to unfair bias in test scores. Furthermore, language-dependent assessment tools produce results that are not easily comparable across countries. Here we present results of a study that aims to develop tasks allowing to test for basic math competence without relying on verbal instructions or task content. We implemented video and animation-based task instructions on touchscreen devices that require no verbal explanation. We administered these experimental tasks to two samples of children attending the first grade of primary school. One group completed the tasks with verbal instructions while another group received video instructions showing a person successfully completing the task. We assessed task comprehension and usability aspects both directly and indirectly. Our results suggest that the non-verbal instructions were generally well understood as the absence of explicit verbal instructions did not influence task performance. Thus we found that it is possible to assess basic math competence without verbal instructions. It also appeared that in some cases a single word in a verbal instruction can lead to the failure of a task that is successfully completed with non-verbal instruction. However, special care must be taken during task design because on rare occasions non-verbal video instructions fail to convey task instructions as clearly as spoken language and thus the latter do not provide a panacea to non-verbal assessment. Nevertheless, our findings provide an encouraging proof of concept for the further development of non-verbal assessment tools for basic math competence

Separation of atomic and molecular ions by ion mobility with an RF carpet

Gas-filled stopping cells are used at accelerator laboratories for the thermalization of high-energy radioactive ion beams. Common challenges of many stopping cells are a high molecular background of extracted ions and limitations of extraction efficiency due to space-charge effects. At the FRS Ion Catcher at GSI, a new technique for removal of ionized molecules prior to their extraction out of the stopping cell has been developed. This technique utilizes the RF carpet for the separation of atomic ions from molecular contaminant ions through their difference in ion mobility. Results from the successful implementation and test during an experiment with a 600~MeV/u $^{124}$Xe primary beam are presented. Suppression of molecular contaminants by three orders of magnitude has been demonstrated. Essentially background-free measurement conditions with less than $1~\%$ of background events within a mass-to-charge range of 25 u/e have been achieved. The technique can also be used to reduce the space-charge effects at the extraction nozzle and in the downstream beamline, thus ensuring high efficiency of ion transport and highly-accurate measurements under space-charge-free conditions.Comment: 8 pages, 4 figure

Rac1 Regulates the NLRP3 Inflammasome Which Mediates IL-1beta Production in Chlamydophila pneumoniae Infected Human Mononuclear Cells

Chlamydophila pneumoniae causes acute respiratory tract infections and has been associated with development of asthma and atherosclerosis. The production of IL-1β, a key mediator of acute and chronic inflammation, is regulated on a transcriptional level and additionally on a posttranslational level by inflammasomes. In the present study we show that C. pneumoniae-infected human mononuclear cells produce IL-1β protein depending on an inflammasome consisting of NLRP3, the adapter protein ASC and caspase-1. We further found that the small GTPase Rac1 is activated in C. pneumoniae-infected cells. Importantly, studies with specific inhibitors as well as siRNA show that Rac1 regulates inflammasome activation in C. pneumoniae-infected cells. In conclusion, C. pneumoniae infection of mononuclear cells stimulates IL-1β production dependent on a NLRP3 inflammasome-mediated processing of proIL-1β which is controlled by Rac1