Unsupervised network analysis of the plastic supraoptic nucleus transcriptome predicts caprin2 regulatory interactions

AbstractThe supraoptic nucleus (SON) is a group of neurons in the hypothalamus responsible for the synthesis and secretion of the peptide hormones vasopressin and oxytocin. Following physiological cues, such as dehydration, salt-loading and lactation, the SON undergoes a function related plasticity that we have previously described in the rat at the transcriptome level. Using the unsupervised graphical lasso (Glasso) algorithm, we reconstructed a putative network from 500 plastic SON genes in which genes are the nodes and the edges are the inferred interactions. The most active nodal gene identified within the network wasCaprin2.Caprin2encodes an RNA-binding protein that we have previously shown to be vital for the functioning of osmoregulatory neuroendocrine neurons in the SON of the rat hypothalamus. To test the validity of the Glasso network, we either overexpressed or knocked downCaprin2transcripts in differentiated rat pheochromocytoma PC12 cells and showed that these manipulations had significant opposite effects on the levels of putative target mRNAs. These studies suggest that the predicative power of the Glasso algorithm within anin vivosystem is accurate, and identifies biological targets that may be important to the functional plasticity of the SON.</jats:p

Prospects for SIMPLE 2000: A large-mass, low-background Superheated Droplet Detector for WIMP searches

SIMPLE 2000 (Superheated Instrument for Massive ParticLE searches) will consist of an array of eight to sixteen large active mass ($\sim15$ g) Superheated Droplet Detectors(SDDs) to be installed in the new underground laboratory of Rustrel-Pays d'Apt. Several factors make of SDDs an attractive approach for the detection of Weakly Interacting Massive Particles (WIMPs), namely their intrinsic insensitivity to minimum ionizing particles, high fluorine content, low cost and operation near ambient pressure and temperature. We comment here on the fabrication, calibration and already-competitive first limits from SIMPLE prototype SDDs, as well as on the expected immediate increase in sensitivity of the program, which aims at an exposure of $>$25 kg-day during the year 2000. The ability of modest-mass fluorine-rich detectors to explore regions of neutralino parameter space beyond the reach of the most ambitious cryogenic projects is pointed out.Comment: 19 pages, 10 figures included. New Journal of Physics, in pres

The Generation R Study: design and cohort update 2010

The Generation R Study is a population-based prospective cohort study from fetal life until young adulthood. The study is designed to identify early environmental and genetic causes of normal and abnormal growth, development and health during fetal life, childhood and adulthood. The study focuses on four primary areas of research: (1) growth and physical development; (2) behavioural and cognitive development; (3) diseases in childhood; and (4) health and healthcare for pregnant women and children. In total, 9,778 mothers with a delivery date from April 2002 until January 2006 were enrolled in the study. General follow-up rates until the age of 4 years exceed 75%. Data collection in mothers, fathers and preschool children included questionnaires, detailed physical and ultrasound examinations, behavioural observations, and biological samples. A genome wide association screen is available in the participating children. Regular detailed hands on assessment are performed from the age of 5 years onwards. Eventually, results forthcoming from the Generation R Study have to contribute to the development of strategies for optimizing health and healthcare for pregnant women and children