Architectural Control of Mesenchymal Stem Cell Phenotype Through Nuclear Actin

There is growing appreciation that architectural components of the nucleus regulate gene accessibility by altering chromatin organization. While nuclear membrane connector proteins link the mechanosensitive actin cytoskeleton to the nucleoskeleton, actin’s contribution to the inner architecture of the nucleus remains enigmatic. Control of actin transport into the nucleus, plus the presence of proteins that control actin structure (the actin tool-box) within the nucleus, suggests that nuclear actin may support biomechanical regulation of gene expression. Cellular actin structure is mechanoresponsive: actin cables generated through forces experienced at the plasma membrane transmit force into the nucleus. We posit that dynamic actin remodeling in response to such biomechanical cues provides a novel level of structural control over the epigenetic landscape. We here propose to bring awareness to the fact that mechanical forces can promote actin transfer into the nucleus and control structural arrangements as illustrated in mesenchymal stem cells, thereby modulating lineage commitment

Grammatical performance in children with dyslexia: the contributions of individual differences in phonological memory and statistical learning

Several studies have signaled grammatical difficulties in individuals with developmental dyslexia. These difficulties may stem from a phonological deficit, but may alternatively be explained through a domain-general deficit in statistical learning. This study investigates grammar in children with and without dyslexia, and whether phonological memory and/or statistical learning ability contribute to individual differences in grammatical performance. We administered the CELF word structure and recalling sentences subtests and measures of phonological memory (digit span, nonword repetition) and statistical learning (serial reaction time, nonadjacent dependency learning) among 8-to 11-year-old children with and without dyslexia (N = 50 per group). Consistent with previous findings, our results show subtle difficulties in grammar, as children with dyslexia achieved lower scores on the CELF (word structure: p =.0027, recalling sentences: p =.053). While the two phonological memory measures were found to contribute to individual differences in grammatical performance, no evidence for a relationship with statistical learning was found. An error analysis revealed errors in irregular morphology (e.g., plural and past tense), suggesting problems with lexical retrieval. These findings are discussed in light of theoretical accounts of the underlying deficit in dyslexia

Auditory statistical learning in children: Novel insights from an online measure

Nonadjacent dependency learning is thought to be a fundamental skill for syntax acquisition and often assessed via an offline grammaticality judgment measure. Asking judgments of children is problematic, and an offline task is suboptimal as it reflects only the outcome of the learning process, disregarding information on the learning trajectory. Therefore, and following up on recent methodological advancements in the online measurement of nonadjacent dependency learning in adults, the current study investigates if the recording of response times can be used to establish nonadjacent dependency learning in children. Forty-six children (mean age: 7.3 years) participated in a child-friendly adaptation of a nonadjacent dependency learning experiment (López-Barroso, Cucurell, Rodríguez-Fornells, & de Diego-Balaguer, 2016). They were exposed to an artificial language containing items with and without nonadjacent dependencies while their response times (online measure) were measured. After exposure, grammaticality judgments (offline measure) were collected. The results show that children are sensitive to nonadjacent dependencies, when using the online measure (the results of our offline measure did not provide evidence of learning). We therefore conclude that future studies can use online response time measures (perhaps in addition to the offline grammaticality judgments) to further investigate nonadjacent dependency learning in children

Resolving intertracer inconsistencies in soil ingestion estimation.

In this article we explore sources and magnitude of positive and negative error in soil ingestion estimates for children on a subject-week and trace element basis. Errors varied among trace elements. Yttrium and zirconium displayed predominantly negative error; titanium and vanadium usually displayed positive error. These factors lead to underestimation of soil ingestion estimates by yttrium and zirconium and a large overestimation by vanadium. The most reliable tracers for soil ingestion estimates were aluminum, silicon, and yttrium. However, the most reliable trace element for a specific subject-day (or week) would be the element with the least error during that time period. The present analysis replaces our previous recommendations that zirconium and titanium are the most reliable trace elements in estimating soil ingestion by children. This report identifies limitations in applying the biostatistical model based on data for adults to data for children. The adult-based model used data less susceptible to negative bias and more susceptible to source error (positive bias) for titanium and vanadium than the data for children. These factors contributed significantly to inconsistencies in model predictions of soil ingestion rates for children. Correction for error at the subject-day level provides a foundation for generation of subject-specific daily soil ingestion distributions and for linking behavior to soil ingestion

The Role of RUNX2 in Osteosarcoma Oncogenesis

Osteosarcoma is an aggressive but ill-understood cancer of bone that predominantly affects adolescents. Its rarity and biological heterogeneity have limited studies of its molecular basis. In recent years, an important role has emerged for the RUNX2 “platform protein” in osteosarcoma oncogenesis. RUNX proteins are DNA-binding transcription factors that regulate the expression of multiple genes involved in cellular differentiation and cell-cycle progression. RUNX2 is genetically essential for developing bone and osteoblast maturation. Studies of osteosarcoma tumours have revealed that the RUNX2 DNA copy number together with RNA and protein levels are highly elevated in osteosarcoma tumors. The protein is also important for metastatic bone disease of prostate and breast cancers, while RUNX2 may have both tumor suppressive and oncogenic roles in bone morphogenesis. This paper provides a synopsis of the current understanding of the functions of RUNX2 and its potential role in osteosarcoma and suggests directions for future study