Differential Effects of the Home Language and Literacy Environment on Child Language and Theory of Mind and Their Relation to Socioeconomic Background.

In this study, we examined differential effects of facets of the home language and literacy environment that are known to be relevant to either language development (i.e., quantity and quality of language and literacy stimulation at home) or theory of mind (ToM) development (i.e., parental mental state language), on both children's language skills and their ToM understanding. Moreover, we investigated whether these relations are particularly relevant for children from homes with low socioeconomic status (SES) and whether they account for SES-related disparities in child language skills and ToM understanding. Using longitudinal data of a sample of 224 monolingual German preschool children (assessment of language skills at age 4;6 and 5;6 and ToM at age 5;6), we analyzed the effects of three facets of the home language and literacy environment on later child language and ToM understanding. These facets were book exposure as a measure for quantity of language and literacy stimulation at home, quality of verbal interaction, and parental mental state language assessed between ages 3 and 4. Path analyses showed that book exposure is related to both later ToM understanding and language skills at age 5;6 years; yet, this effect is mediated by earlier language skills at age 4;6 years. Furthermore, book exposure partly mediated the association between SES and language skills and, via earlier language skills at age 4;6, also the relation between SES and ToM. When focusing on children from lower SES families, book exposure and quality of verbal stimulation predicted children's later language skills at age 4;6. Book exposure also predicted change in language skills between age 4;6 and age 5;6. Further, book exposure proved to be significantly associated with children's ToM understanding at age 5;6 via the relation with language skills at 4;6 years. In addition, parental mental state language predicted children's ToM understanding at age 5;6 years. Our findings provide new evidence on how different facets of the home language and literacy environment are related to ToM and language development and their interrelation as well as their SES-related disparities.

Early Language Competencies and Advanced Measures of Mental State Understanding Are Differently Related to Listening and Reading Comprehension in Early Adolescence.

The present study tests a section of the DIET (direct and indirect effects model of text comprehension; Kim, 2017) model and focuses on the relations between early language skills, various facets of mental state understanding, and text comprehension. In a sample of 267 children, I analyzed the relations between language skills (vocabulary, sentence comprehension) at age 3;6, theory of mind (ToM) at age 5;6, mental state language and metacognitive knowledge at age 9;2, and children's listening and reading comprehension of texts at age 13;7 years. For reading comprehension, results favored a total mediation model that included only direct links from metacognitive knowledge and mental state language to reading comprehension. For listening comprehension, by contrast, a model that also included direct relations from language and ToM in preschool was favored. Metacognitive skills did not mediate the relation between early skills and later text comprehension but, along with mental state language, showed direct relations with reading comprehension beyond listening comprehension. Early language skills showed various indirect relations with later reading comprehension via ToM, mental state language, and listening comprehension, whereas ToM showed only small indirect relations with later reading comprehension via later listening comprehension. These different relations of the various components with later listening in contrast to reading comprehension are discussed.

Theory of mind, language, and reading: Developmental relations from early childhood to early adolescence.

This study longitudinally investigated the relation between theory of mind (ToM) and verbal language skills in 231 children from preschool to early adolescence. Further, links to reading comprehension of texts at age 13;7 (years;months) were examined. To assess ToM, children completed false belief tasks at 5;6 and the Strange Stories at 12;8. To assess language, children completed a receptive grammar/sentence comprehension test at 3;6 and 5;6, a receptive vocabulary test at 3;6, 5;6 and 12;8, as well as a test of listening comprehension of texts at 13;7. A bidirectional relation between early and advanced measures of children's language skills and ToM was found: Changes in ToM were predicted by language skills, especially by receptive grammar/sentence comprehension; changes in children's receptive vocabulary were predicted by early ToM. However, early ToM had no direct or indirect effect on later listening comprehension or reading comprehension after controlling for early language skills. Only children's advanced ToM had a small indirect effect on reading comprehension, via listening comprehension. The results are discussed in light of ToM stability over time, and theories on how language and ToM development are intertwined.

High-throughput rheological measurements with an optical stretcher.

The cytoskeleton is a major determinant of the mechanical strength and morphology of most cells. The composition and assembly state of this intracellular polymer network evolve during the differentiation of cells, and the structure is involved in many cellular functions and is characteristically altered in many diseases, including cancer. Here we exploit the deformability of the cytoskeleton as a link between molecular structure and biological function, to distinguish between cells in different states by using a laser-based optical stretcher (OS) coupled with microfluidic handling of cells. An OS is a cell-sized, dual-beam laser trap designed to nondestructively test the deformability of single suspended cells. Combined with microfluidic delivery, many cells can be measured serially in a short amount of time. With this tool it could be shown that optical deformability is sensitive enough to monitor subtle changes during the progression of cells from normal to cancerous and even a metastatic state. Stem cells can also be distinguished from more differentiated cells. The surprisingly low number of cells required for this assay reflects the tight regulation of the cytoskeleton by the cell. This suggests the possibility of using optical deformability as an inherent cell marker for basic cell biological investigation, diagnosis of disease, and sorting of stem cells from heterogeneous populations, obviating the need for external markers or special preparation. Many additional biological assays can be easily adapted to utilize this innovative physical method. This chapter details the setup and use of the microfluidic OS, the analysis and interpretation of data, and the results of a typical experiment.

Reconfigurable microfluidic integration of a dual-beam laser trap with biomedical applications.

A dual-beam fiber laser trap, termed the optical stretcher when used to deform objects, has been combined with a capillary-based microfluidic system in order to serially trap and deform biological cells. The design allows for control over the size and position of the trap relative to the flow channel. Data is recorded using video phase contrast microscopy and is subsequently analyzed using a custom edge fitting routine. This setup has been regularly used with measuring rates of 50-100 cells/h. One such experiment is presented to compare the distribution of deformability found within a normal epithelial cell line to that of a cancerous one. In general, this microfluidic optical stretcher can be used for the characterization of cells by their viscoelastic signature. Possible applications include the cytological diagnosis of cancer and the gentle and marker-free sorting of stem cells from heterogeneous populations for therapeutic cell-based approaches in regenerative medicine.

Fluorescence ratio thermometry in a microfluidic dual-beam laser trap.

The dual-beam laser trap is a versatile tool with many possible applications. In order to characterize its thermal properties in a microfluidic trap geometry we have developed a non-intrusive fluorescence ratio technique using the temperature sensitive dye Rhodamine B and the temperature independent reference dye Rhodamine 110. We measured temperature distribution profiles in the trap with submicron spatial resolution on a confocal laser-scanning microscope. The maximum heating in the center of the trap amounts to (13 +/- 2) degrees C/W for a wavelength of lambda = 1064 nm and scales linearly with the applied power. The measurements correspond well with simulated temperature distributions.

Formation of a freely suspended membrane via a combination of interfacial reaction and wetting.

Applying poly(ethoxysiloxane) (a liquid non-water-soluble polymer that can be hydrolyzed and cross-linked by diluted acids) to an air/pH 1 water interface gave rise to thin homogeneous solid layers. These layers were strong enough to be transferable to electron microscopy grids with holes of dimensions up to 150 microm and covered the holes as freely suspended membranes. No homogeneous layers were formed at an air/pH 5 water interface. Brewster angle microscopy images show that the poly(ethoxysiloxane) is not spontaneously forming a wetting layer on water. It initially forms lenses, which slowly spread out within several hours. We conclude that the spreading occurs simultaneously with the hydrolysis and cross-linking of the poly(ethoxysiloxane) and that the reaction products finally assist the complete wetting of the water surface.

Optical deformability as an inherent cell marker for testing malignant transformation and metastatic competence.

The relationship between the mechanical properties of cells and their molecular architecture has been the focus of extensive research for decades. The cytoskeleton, an internal polymer network, in particular determines a cell's mechanical strength and morphology. This cytoskeleton evolves during the normal differentiation of cells, is involved in many cellular functions, and is characteristically altered in many diseases, including cancer. Here we examine this hypothesized link between function and elasticity, enabling the distinction between different cells, by using a microfluidic optical stretcher, a two-beam laser trap optimized to serially deform single suspended cells by optically induced surface forces. In contrast to previous cell elasticity measurement techniques, statistically relevant numbers of single cells can be measured in rapid succession through microfluidic delivery, without any modification or contact. We find that optical deformability is sensitive enough to monitor the subtle changes during the progression of mouse fibroblasts and human breast epithelial cells from normal to cancerous and even metastatic state. The surprisingly low numbers of cells required for this distinction reflect the tight regulation of the cytoskeleton by the cell. This suggests using optical deformability as an inherent cell marker for basic cell biological investigation and diagnosis of disease.

Characterizing single suspended cells by optorheology.

The measurement of the mechanical properties of individual cells has received much attention in recent years. In this paper we describe the application of optically induced forces with an optical stretcher to perform step-stress experiments on individual suspended fibroblasts. The conversion from creep-compliance to frequency-dependent complex shear modulus reveals characteristic viscoelastic signatures of the underlying cytoskeleton and its dynamic molecular properties. Both normal and cancerous fibroblasts display a single stress relaxation time in the observed time and frequency space that can be related to the transient binding of actin crosslinking proteins. In addition, shear modulus and steady-state viscosity of the shell-like actin cortex as the main module resisting small deformations are extracted. These values in combination with insight into the cells' architecture are used to explain their different deformability. This difference can then be exploited to distinguish normal from cancerous cells. The nature of the optical stretcher as an optical trap allows easy incorporation in a microfluidic system with automatic trapping and alignment of the cells, and thus a high measurement throughput. This carries the potential for using the microfluidic optical stretcher to investigate cellular processes involving the cytoskeleton and to diagnose diseases related to cytoskeletal alterations.