Executive function and IQ predict mathematical and attention problems in very preterm children

Objective of this study was to examine the impact of executive function (EF) on mathematical and attention problems in very preterm (gestational age ≤ 30 weeks) children. Participants were 200 very preterm (mean age 8.2 ± 2.5 years) and 230 term children (mean age 8.3 ± 2.3 years) without severe disabilities, born between 1996 and 2004. EFs assessed included verbal fluency, verbal working memory, visuospatial span, planning, and impulse control. Mathematics was assessed with the Dutch Pupil Monitoring System and parents and teachers rated attention problems using standardized behavior questionnaires. The impact of EF was calculated over and above processi

A quantitative LumiFluo assay to test inhibitory compounds blocking p53 degradation induced by human papillomavirus oncoprotein E6 in living cells

High-risk human papillomaviruses (HR-HPVs) are the causative agents for the onset of several epithelial cancers in humans. The deregulated expression of the viral oncoproteins E6 and E7 is the driving force sustaining the progression of malignant transformation in pre-neoplastic lesions. Targeting the viral E6 oncoprotein through inhibitory compounds can counteract the survival of cancer cells due to the reactivation of p53-mediated pathways and represents an intriguing strategy to treat HPV-associated neoplasias. Here, we describe the development of a quantitative and easy-to-perform assay to monitor the E6-mediated degradation of p53 in living cells to be used for small-molecule testing. This assay allows to unbiasedly determine whether a compound can protect p53 from the E6-mediated degradation in cells, through a simple 3-step protocol. We validated the assay by testing two small molecules, SAHA and RITA, reported to impair the E6-mediated p53 degradation. Interestingly, we observed that only SAHA efficiently rescued p53, while RITA could not provide the same degree of protection. The possibility to specifically and quantitatively monitor the ability of a selected compound to rescue p53 in a cellular context through our LumiFluo assay could represent an important step towards the successful development of anti-HPV drugs

Polycomb group proteins: navigators of lineage pathways led astray in cancer

Udgivelsesdato: 2009-NovThe Polycomb group (PcG) proteins are transcriptional repressors that regulate lineage choices during development and differentiation. Recent studies have advanced our understanding of how the PcG proteins regulate cell fate decisions and how their deregulation potentially contributes to cancer. In this Review we discuss the emerging roles of long non-coding RNAs (ncRNAs) and a subset of transcription factors, which we call cell fate transcription factors, in the regulation of PcG association with target genes. We also speculate about how their deregulation contributes to tumorigenesis

Ichnology of a marine regressive systems tract: the Middle Triassic of Svalbard

The Middle Triassic succession of Svalbard forms a pronounced second-order transgressive–regressive sequence. This is represented by deltaic sediments in western Spitsbergen, grading to deep restricted shelf deposits in central and eastern parts of the archipelago. Nine ichnogenera have been recognized, which form three local ichnofacies or trace fossil assemblages: a Thalassinoides assemblage that is dominant in low-energy shelf settings, a Taenidium– Rhizocorallium assemblage that occurs in intermediate-energy deltaic and shelf environments, and a Polykladichnus assemblage that dominates high-energy deltaic environments. These three trace fossil assemblages overlap, both as a result of fluctuations in energy level with time and because of differential preservation of the different tiers. The main control of the distribution of the assemblages is an upwards increase in energy regime during progradation of the deltaic sediments along western Spitsbergen, and a contemporaneous decrease in energy regime more distally. The succession has also experienced fluctuating oxygen levels during deposition, as evidenced by very high organic matter contents and mass mortality of juvenile bivalves. These anoxic periods have been interrupted by periods of bioturbation, with the development of extensive tiered ichnocoenoses. Phosphatization of Thalassinoides fills and subsequent modification of the phosphatic fill by compaction has brought about the formation of phosphate nodules. The typical Thalassinoides framework may be recognized on well-exposed bedding surfaces. The phosphate nodules also occur as conglomeratic lag deposits, commonly occurring at the base of siltstone beds, as a result of episodic heavy storms