Elevated fetal steroidogenic activity in autism

Autism affects males more than females, giving rise to the idea that the influence of steroid hormones on early fetal brain development may be one important early biological risk factor. Utilizing the Danish Historic Birth Cohort and Danish Psychiatric Central Register, we identified all amniotic fluid samples of males born between 1993 and 1999 who later received ICD-10 (International Classification of Diseases, 10th Revision) diagnoses of autism, Asperger syndrome or PDD-NOS (pervasive developmental disorder not otherwise specified) (n=128) compared with matched typically developing controls. Concentration levels of Δ4 sex steroids (progesterone, 17α-hydroxy-progesterone, androstenedione and testosterone) and cortisol were measured with liquid chromatography tandem mass spectrometry. All hormones were positively associated with each other and principal component analysis confirmed that one generalized latent steroidogenic factor was driving much of the variation in the data. The autism group showed elevations across all hormones on this latent generalized steroidogenic factor (Cohen's d=0.37, P=0.0009) and this elevation was uniform across ICD-10 diagnostic label. These results provide the first direct evidence of elevated fetal steroidogenic activity in autism. Such elevations may be important as epigenetic fetal programming mechanisms and may interact with other important pathophysiological factors in autism

The DAG1 transcription factor negatively regulates the seed-to-seedling transition in Arabidopsis acting on ABA and GA levels

BACKGROUND: In seeds, the transition from dormancy to germination is regulated by abscisic acid (ABA) and gibberellins (GAs), and involves chromatin remodelling. Particularly, the repressive mark H3K27 trimethylation (H3K27me3) has been shown to target many master regulators of this transition. DAG1 (DOF AFFECTING GERMINATION1), is a negative regulator of seed germination in Arabidopsis, and directly represses the GA biosynthetic gene GA3ox1 (gibberellin 3-β-dioxygenase 1). We set to investigate the role of DAG1 in seed dormancy and maturation with respect to epigenetic and hormonal control. RESULTS: We show that DAG1 expression is controlled at the epigenetic level through the H3K27me3 mark during the seed-to-seedling transition, and that DAG1 directly represses also the ABA catabolic gene CYP707A2; consistently, the ABA level is lower while the GA level is higher in dag1 mutant seeds. Furthermore, both DAG1 expression and protein stability are controlled by GAs. CONCLUSIONS: Our results point to DAG1 as a key player in the control of the developmental switch between seed dormancy and germination

A Methodology for the Diagnostic of Aircraft Engine Based on Indicators Aggregation

Aircraft engine manufacturers collect large amount of engine related data during flights. These data are used to detect anomalies in the engines in order to help companies optimize their maintenance costs. This article introduces and studies a generic methodology that allows one to build automatic early signs of anomaly detection in a way that is understandable by human operators who make the final maintenance decision. The main idea of the method is to generate a very large number of binary indicators based on parametric anomaly scores designed by experts, complemented by simple aggregations of those scores. The best indicators are selected via a classical forward scheme, leading to a much reduced number of indicators that are tuned to a data set. We illustrate the interest of the method on simulated data which contain realistic early signs of anomalies.Comment: Proceedings of the 14th Industrial Conference, ICDM 2014, St. Petersburg : Russian Federation (2014

Identification of Structural Variation in Chimpanzees Using Optical Mapping and Nanopore Sequencing.

Recent efforts to comprehensively characterize great ape genetic diversity using short-read sequencing and single-nucleotide variants have led to important discoveries related to selection within species, demographic history, and lineage-specific traits. Structural variants (SVs), including deletions and inversions, comprise a larger proportion of genetic differences between and within species, making them an important yet understudied source of trait divergence. Here, we used a combination of long-read and -range sequencing approaches to characterize the structural variant landscape of two additional Pan troglodytes verus individuals, one of whom carries 13% admixture from Pan troglodytes troglodytes. We performed optical mapping of both individuals followed by nanopore sequencing of one individual. Filtering for larger variants (>10 kbp) and combined with genotyping of SVs using short-read data from the Great Ape Genome Project, we identified 425 deletions and 59 inversions, of which 88 and 36, respectively, were novel. Compared with gene expression in humans, we found a significant enrichment of chimpanzee genes with differential expression in lymphoblastoid cell lines and induced pluripotent stem cells, both within deletions and near inversion breakpoints. We examined chromatin-conformation maps from human and chimpanzee using these same cell types and observed alterations in genomic interactions at SV breakpoints. Finally, we focused on 56 genes impacted by SVs in >90% of chimpanzees and absent in humans and gorillas, which may contribute to chimpanzee-specific features. Sequencing a greater set of individuals from diverse subspecies will be critical to establish the complete landscape of genetic variation in chimpanzees

Nanoparticles in the treatment of chronic lung diseases

Nanoparticles, although considered a topic of modern medicine, actually have an interesting history. Currently, advances in nanomedicine hold great promise as drug carrier systems for sustained release and targeted delivery of diverse therapeutic agents. Nanoparticles can be defined as complex drug carrier systems which incorporate and protect a certain drug or particle. Nanoparticles can be administered via different routes, such as intravenous injection, oral administration, or pulmonary inhalation. Even though the use of nano-carriers via pulmonary inhalation is heavily debated, this system represents an attractive alternative to the intravenous or oral routes, due to the unique anatomical and physiological features of the lungs and the minimal interactions between the targeted site and other organs. Some of the widely used nano-carriers for the treatment of chronic pulmonary diseases, via pulmonary route, are as follows: polymeric nanoparticles, liposomal nano-carriers, solid lipid nanoparticles, and submicron emulsions. Nano-carrier systems provide the advantage of sustained-drug release in the lung tissue resulting in reduced dosing frequency and improved patient compliance. Further studies focusing on understanding the mechanisms of action of nanoparticles and improving their chemical structure are required in order to better understand the potential long-term risk of excipient toxicity and nanoscale carriers

Couch-based motion compensation: modelling, simulation and real-time experiments

Abstract The paper presents a couch-based active motion compensation strategy evaluated in simulation and validated experimentally using both a research and a clinical Elekta Precise Table™. The control strategy combines a Kalman filter to predict the surrogate motion used as a reference by a linear model predictive controller with the control action calculation based on estimated position and velocity feedback provided by an observer as well as predicted couch position and velocity using a linearized state space model. An inversion technique is used to compensate for the dead-zone nonlinearity. New generic couch models are presented and applied to model the Elekta Precise Table™ dynamics and nonlinearities including dead zone. Couch deflection was measured for different manufacturers and found to be up to 25 mm. A feed-forward approach is proposed to compensate for such couch deflection. Simultaneous motion compensation for longitudinal, lateral and vertical motions was evaluated using arbitrary trajectories generated from sensors or loaded from files. Tracking errors were between 0.5 and 2 mm RMS. A dosimetric evaluation of the motion compensation was done using a sinusoidal waveform. No notable differences were observed between films obtained for a fixed- or motion-compensated target. Further dosimetric improvement could be made by combining gating, based on tracking error together with beam on/off time, and PSS compensation.</jats:p