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

Geluidmonitor 2014

Het RIVM heeft in 2013 geluidmetingen verricht op 23 locaties langs rijkswegen en op 26 locaties langs spoorwegen. Langs rijkswegen bleek het gemiddelde geluidniveau substantieel (2,4 decibel) hoger te liggen dan de berekende waarde. Langs het spoor was er gemiddeld geen significant verschil (0,5 dB). Afhankelijk van de meetlocatie kunnen de verschillen groter of kleiner zijn. De verschillen langs rijkswegen worden veroorzaakt door het feit dat de wettelijk voorgeschreven rekenmethode uitgaat van stille banden op een droog wegdek bij een standaardtemperatuur van 20 graden Celsius. De omstandigheden zijn vaak ongunstiger. Daarnaast draagt de variatie in akoestische kwaliteit van het wegdek bij aan de verschillen. Het meetprogramma vloeit voort uit een motie van de Tweede Kamer naar aanleiding van geluidwetgeving uit 2012. De wet stelt grenswaarden aan het geluid langs rijkswegen en spoorwegen. De wegen spoorbeheerder (Rijkswaterstaat en ProRail) dienen met een jaarlijkse berekening aan te tonen hieraan te voldoen. Onderdeel van de wet is ook een validatie van de rekenuitkomsten met metingen. Het RIVM verricht hiertoe jaarlijks geluidmetingen en vergelijkt die met de berekende geluidproductie die de weg- en spoorbeheerder rapporteren. Dit rapport gaat in op de verschillen tussen reken en meetresultaten in 2013. Het rapport geeft ook de meetresultaten uit 2014 langs rijkswegen en spoorwegen op 92 meetlocaties. Deze zullen worden vergeleken met de rekenresultaten die door de weg- en spoorbeheerder gepubliceerd worden in september 2015. Hierover zal het RIVM in 2016 rapporteren. Als blijkt dat de verschillen tussen de meet- en rekenwaarden structureel zijn, is nader onderzoek nodig naar de gezondheidskundige relevantie voor de Nederlandse bevolking en naar de vraag of aanpassingen van de rekenmethode nodig zijn.In 2013 RIVM has conducted noise measurements at 23 locations along motorways and at 26 locations along railways. Along motorways, the average measured noise level was substantially (2,4 dB) higher than the calculated value. Along the track, on average no significant difference was found (0,5 dB). Depending on the measurement location, larger or smaller differences can be found. The differences along motorways are partly due to the calculation method, which is based on low-noise tires on dry surfaces at a standard temperature of 20 degrees Celsius. The average conditions are less favorable. Also the variation in acoustic quality of the road surface contributes to the differences. For rail, no clear causes of differences are yet to be declared. The measurement program stems from a motion of the House in response to noise legislation (Swung) proposed and accepted in 2012. This Act sets limits on noise along motorways and railways. The administrators, Rijkswaterstaat and ProRail, annually demonstrate by a statutory calculation to fulfill this requirement. The legislation also requires validation of the calculation results by measurements. To this aim RIVM annually conducts measurements and compares the results with the calculated noise production as reported by the road- and railway administrator. This report discusses the differences between calculation and measurement results in 2013. It also contains the measurement results from 2014, along motorways and railroads on a sample of 92 measuring sites. These results will be compared with the calculation results, after they are published in September 2015 by the road- and railway administrator. If it appears that the differences between measurement and calculation are structural, further research is needed into the health implications for the Dutch population and whether adjustments to the calculation methods are needed.Ministerie van I&

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