Divergent dysregulation of gene expression in murine models of fragile X syndrome and tuberous sclerosis

Background: Fragile X syndrome and tuberous sclerosis are genetic syndromes that both have a high rate of comorbidity with autism spectrum disorder (ASD). Several lines of evidence suggest that these two monogenic disorders may converge at a molecular level through the dysfunction of activity-dependent synaptic plasticity. Methods: To explore the characteristics of transcriptomic changes in these monogenic disorders, we profiled genome-wide gene expression levels in cerebellum and blood from murine models of fragile X syndrome and tuberous sclerosis. Results: Differentially expressed genes and enriched pathways were distinct for the two murine models examined, with the exception of immune response-related pathways. In the cerebellum of the Fmr1 knockout (Fmr1-KO) model, the neuroactive ligand receptor interaction pathway and gene sets associated with synaptic plasticity such as long-term potentiation, gap junction, and axon guidance were the most significantly perturbed pathways. The phosphatidylinositol signaling pathway was significantly dysregulated in both cerebellum and blood of Fmr1-KO mice. In Tsc2 heterozygous (+/−) mice, immune system-related pathways, genes encoding ribosomal proteins, and glycolipid metabolism pathways were significantly changed in both tissues. Conclusions: Our data suggest that distinct molecular pathways may be involved in ASD with known but different genetic causes and that blood gene expression profiles of Fmr1-KO and Tsc2+/− mice mirror some, but not all, of the perturbed molecular pathways in the brain

Obscured Activity: AGN, Quasars, Starbursts and ULIGs observed by the Infrared Space Observatory

Some of the most active galaxies in the Universe are obscured by large quantities of dust and emit a substantial fraction of their bolometric luminosity in the infrared. Observations of these infrared luminous galaxies with the Infrared Space Observatory (ISO) have provided a relatively unabsorbed view to the sources fuelling this active emission. The improved sensitivity, spatial resolution and spectroscopic capability of ISO over its predecessor Infrared Astronomical Satellite (IRAS), has enabled significant advances in the understanding of the infrared properties of active galaxies. ISO surveyed a wide range of active galaxies which, in the context of this review, includes those powered by intense bursts of star-formation as well as those containing a dominant active galactic nucleus (AGN). Mid infrared imaging resolved for the first time the dust enshrouded nuclei in many nearby galaxies, while a new era in infrared spectroscopy was opened by probing a wealth of atomic, ionic and molecular lines as well as broad band features in the mid and far infrared. This was particularly useful since it resulted in the understanding of the power production, excitation and fuelling mechanisms in the nuclei of active galaxies including the intriguing but so far elusive ultraluminous infrared galaxies. Detailed studies of various classes of AGN and quasars greatly improved our understanding of the unification scenario. Far-infrared imaging and photometry also revealed the presence of a new very cold dust component in galaxies and furthered our knowledge of the far-infrared properties of faint starbursts, ULIGs and quasars. We summarise almost nine years of key results based upon ISO data spanning the full range of luminosity and type of active galaxies.Comment: Accepted for publication in 'ISO science legacy - a compact review of ISO major achievements', Space Science Reviews - dedicated ISO issue. To be published by Springer in 2005. 62 pages (low resolution figures version). Higher resolution PDFs available from http://users.physics.uoc.gr/~vassilis/papers/VermaA.pdf or http://www.iso.vilspa.esa.es/science/SSR/Verma.pd

The continued need for animals to advance brain research

Policymakers aim to move toward animal-free alternatives for scientific research and have introduced very strict regulations for animal research. We argue that, for neuroscience research, until viable and translational alternatives become available and the value of these alternatives has been proven, the use of animals should not be compromised