Flanker performance in female college students with ADHD: a diffusion model analysis

Attention-deficit hyperactivity disorder (ADHD) is characterized by poor adaptation to environmental demands, which leads to various everyday life problems. The present study had four aims: (1) to compare performance in a flanker task in female college students with and without ADHD (N = 39) in a classical analyses of reaction time and error rate and studying the underlying processes using a diffusion model, (2) to compare the amount of focused attention, (3) to explore the adaptation of focused attention, and (4) to relate adaptation to psychological functioning. The study followed a 2-between (group: ADHD vs. control) × 2-within (flanker conflict: incongruent vs. congruent) × 2-within (conflict frequency: 20 vs. 80 %) design. Compared to a control group, the ADHD group displayed prolonged response times accompanied by fewer errors in a flanker task. Results from the diffusion model analyses revealed that the members of the ADHD group showed deficits in non-decisional processes (i.e., higher non-decision time) and leaned more toward accuracy than participants without ADHD (i.e., setting higher boundaries). The ADHD group showed a more focused attention and less adaptation to the task conditions which is related to psychological functioning. Deficient non-decisional processes and poor adaptation are in line with theories of ADHD and presumably typical for the ADHD population, although this has not been shown using a diffusion model. However, we assume that the cautious strategy of trading speed of for accuracy is specific to the subgroup of female college students with ADHD and might be interpreted as a compensation mechanism

Cohesin is required for higher-order chromatin conformation at the imprinted IGF2-H19 locus

Cohesin is a chromatin-associated protein complex that mediates sister chromatid cohesion by connecting replicated DNA molecules. Cohesin also has important roles in gene regulation, but the mechanistic basis of this function is poorly understood. In mammalian genomes, cohesin co-localizes with CCCTC binding factor (CTCF), a zinc finger protein implicated in multiple gene regulatory events. At the imprinted IGF2-H19 locus, CTCF plays an important role in organizing allele-specific higher-order chromatin conformation and functions as an enhancer blocking transcriptional insulator. Here we have used chromosome conformation capture (3C) assays and RNAi-mediated depletion of cohesin to address whether cohesin affects higher order chromatin conformation at the IGF2-H19 locus in human cells. Our data show that cohesin has a critical role in maintaining CTCF-mediated chromatin conformation at the locus and that disruption of this conformation coincides with changes in IGF2 expression. We show that the cohesin-dependent, higher-order chromatin conformation of the locus exists in both G1 and G2 phases of the cell cycle and is therefore independent of cohesin's function in sister chromatid cohesion. We propose that cohesin can mediate interactions between DNA molecules in cis to insulate genes through the formation of chromatin loops, analogous to the cohesin mediated interaction with sister chromatids in trans to establish cohesion

Simultaneous CXCL12 and ESR1 CpG island hypermethylation correlates with poor prognosis in sporadic breast cancer

<p>Abstract</p> <p>Background</p> <p>CXCL12 is a chemokine that is constitutively expressed in many organs and tissues. <it>CXCL12 </it>promoter hypermethylation has been detected in primary breast tumours and contributes to their metastatic potential. It has been shown that the oestrogen receptor α (<it>ESR1</it>) gene can also be silenced by DNA methylation. In this study, we used methylation-specific PCR (MSP) to analyse the methylation status in two regions of the <it>CXCL12 </it>promoter and <it>ESR1 </it>in tumour cell lines and in primary breast tumour samples, and correlated our results with clinicopathological data.</p> <p>Methods</p> <p>First, we analysed <it>CXCL12 </it>expression in breast tumour cell lines by RT-PCR. We also used 5-aza-2'-deoxycytidine (5-aza-CdR) treatment and DNA bisulphite sequencing to study the promoter methylation for a specific region of <it>CXCL12 </it>in breast tumour cell lines. We evaluated <it>CXCL12 </it>and <it>ESR1 </it>methylation in primary tumour samples by methylation-specific PCR (MSP). Finally, promoter hypermethylation of these genes was analysed using Fisher's exact test and correlated with clinicopathological data using the Chi square test, Kaplan-Meier survival analysis and Cox regression analysis.</p> <p>Results</p> <p><it>CXCL12 </it>promoter hypermethylation in the first region (island 2) and second region (island 4) was correlated with lack of expression of the gene in tumour cell lines. In the primary tumours, island 2 was hypermethylated in 14.5% of the samples and island 4 was hypermethylated in 54% of the samples. The <it>ESR1 </it>promoter was hypermethylated in 41% of breast tumour samples. In addition, the levels of ERα protein expression diminished with increased frequency of <it>ESR1 </it>methylation (p < 0.0001). This study also demonstrated that <it>CXCL12 </it>island 4 and <it>ESR1 </it>methylation occur simultaneously at a high frequency (p = 0.0220).</p> <p>Conclusions</p> <p>This is the first study showing a simultaneous involvement of epigenetic regulation for both <it>CXCL12 </it>and <it>ESR1 </it>genes in Brazilian women. The methylation status of both genes was significantly correlated with histologically advanced disease, the presence of metastases and death. Therefore, the methylation pattern of these genes could be used as a molecular marker for the prediction of breast cancer outcome.</p

Protracted timescales of lower crustal growth at the fast-spreading East Pacific Rise

Author Posting. © The Author(s), 2011. This is the author's version of the work. It is posted here by permission of Nature Publishing Group for personal use, not for redistribution. The definitive version was published in Nature Geoscience 5 (2012): 275-278, doi:10.1038/ngeo1378.Formation of the oceanic crust at mid-ocean ridges is a fundamental component of plate tectonics. A majority of the crust at many ridges is composed of plutonic rocks that form by crystallization of mantle-derived magmas within the crust. Recent application of U/Pb dating to samples from in-situ oceanic crust has begun to provide exciting new insight into the timing, duration and distribution of magmatism during formation of the plutonic crust1-4. Previous studies have focused on samples from slow-spreading ridges, however, the time scales and processes of crustal growth are expected to vary with plate spreading rate. Here we present the first high-precision dates from plutonic crust formed at the fast-spreading East Pacific Rise (EPR). Individual zircon minerals yielded dates from 1.420–1.271 million years ago, with uncertainties of ± 0.006–0.081 million years. Within individual samples, zircons record a range of dates of up to ~0.124 million years, consistent with protracted crystallization or assimilation of older zircons from adjacent rocks. The variability in dates is comparable to data from the Vema lithospheric section on the Mid-Atlantic Ridge (MAR)3, suggesting that time scales of magmatic processes in the lower crust may be similar at slow- and fast-spreading ridges.This research was partially funded by NSF grant OCE-0727914 (SAB), a Cardiff University International Collaboration Award (CJL) and NERC grant NE/C509023/1 (CJM).2012-07-2

The Origin of Minus-end Directionality and Mechanochemistry of Ncd Motors

Adaptation of molecular structure to the ligand chemistry and interaction with the cytoskeletal filament are key to understanding the mechanochemistry of molecular motors. Despite the striking structural similarity with kinesin-1, which moves towards plus-end, Ncd motors exhibit minus-end directionality on microtubules (MTs). Here, by employing a structure-based model of protein folding, we show that a simple repositioning of the neck-helix makes the dynamics of Ncd non-processive and minus-end directed as opposed to kinesin-1. Our computational model shows that Ncd in solution can have both symmetric and asymmetric conformations with disparate ADP binding affinity, also revealing that there is a strong correlation between distortion of motor head and decrease in ADP binding affinity in the asymmetric state. The nucleotide (NT) free-ADP (?-ADP) state bound to MTs favors the symmetric conformation whose coiled-coil stalk points to the plus-end. Upon ATP binding, an enhanced flexibility near the head-neck junction region, which we have identified as the important structural element for directional motility, leads to reorienting the coiled-coil stalk towards the minus-end by stabilizing the asymmetric conformation. The minus-end directionality of the Ncd motor is a remarkable example that demonstrates how motor proteins in the kinesin superfamily diversify their functions by simply rearranging the structural elements peripheral to the catalytic motor head domain

Early Childhood Caries among a Bedouin community residing in the eastern outskirts of Jerusalem

<p>Abstract</p> <p>Background</p> <p>ECC is commonly prevalent among underprivileged populations. The Jahalin Bedouin are a severely deprived, previously nomadic tribe, dwelling on the eastern outskirts of Jerusalem. The aim of this study was to assess ECC prevalence and potentially associated variables.</p> <p>Methods</p> <p>102 children aged 12–36 months were visually examined for caries, mothers' anterior dentition was visually subjectively appraised, demographic and health behavior data were collected by interview.</p> <p>Results</p> <p>Among children, 17.6% demonstrated ECC, among mothers, 37.3% revealed "fairly bad" anterior teeth. Among children drinking bottles there was about twice the level of ECC (20.3%) than those breast-fed (13.2%). ECC was found only among children aged more than one year (p < 0.001); more prevalent ECC (55.6%) was found among large (10–13 children) families than among smaller families (1–5 children: 13.5%, 6–9 children: 15.6%) (p = 0.009); ECC was more prevalent among children of less educated mothers (p = 0.037); ECC was more prevalent among mothers with "fairly poor" anterior dentition (p = 0.04). Oral hygiene practices were poor.</p> <p>Conclusion</p> <p>ECC levels in this community were not very high but neither low. This changing population might be on the verge of a wider dental disease "epidemic". Public health efforts clearly need to be invested towards the oral health and general welfare of this community.</p