Somatostatin Is Expressed in FRTL-5 Thyroid Cells and Prevents Thyrotropin-Mediated Down-Regulation of the Cyclin-Dependent Kinase Inhibitor p27kip11

9 pages, 8 figures, 3 tables.Using RT and amplification, we have detected specific RNA transcripts encoding somatostatin in FRTL-5 thyroid cells. This observation indicates that within the thyroid context, expression of somatostatin is not restricted to the parafollicular C cells. Transfection of FRTL-5 cells with constructs containing either the complete somatostatin gene promoter or deletions carrying the cAMP response element-binding site allowed us to demonstrate that transcription of the somatostatin gene is hormonally regulated by TSH. Blockage of somatostatin by specific antibodies resulted in an increased capacity of TSH-induced FRTL-5 cell-conditioned medium to promote cell proliferation, demonstrating that under physiological conditions, somatostatin exerts a cytostatic effect on FRTL-5 cells growth. Somatostatin treatment of FRTL-5 cells resulted in a growth retardation, caused by a dose-response delay in the G1 phase of the cell cycle. This effect appears to be mediated by the cyclin-dependent kinase inhibitor p27kip1, which is clearly down-regulated in FRTL-5 cells treated with TSH and whose expression is reestablished by somatostatin in a dose-dependent manner. Participation of somatostatin in the control of FRTL-5 cell proliferation is in agreement with the detection of specific somatostatin receptor type 2. Flow cytometric assays reveal that FRTL-5 cells transformed with the K-ras oncogene are still sensitive to somatostatin treatment, whereas fully neoplastic FRT cells no longer respond to this peptide. Taking together, the results demonstrate the participation of an autocrine loop in the control of thyroid cell proliferation, and the possibility that this mechanism could be altered in the process of thyroid carcinogenesis.This work was supported by Grants DGICYT (PM97–0065), CAM (08.1/0025/1997), and Fundación Salud 2000 (Spain).Peer reviewe

Genome-wide identification of the genetic basis of amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a complex disease that leads to motor neuron death. Despite heritability estimates of 52%, genome-wide association studies (GWASs) have discovered relatively few loci. We developed a machine learning approach called RefMap, which integrates functional genomics with GWAS summary statistics for gene discovery. With transcriptomic and epigenetic profiling of motor neurons derived from induced pluripotent stem cells (iPSCs), RefMap identified 690 ALS-associated genes that represent a 5-fold increase in recovered heritability. Extensive conservation, transcriptome, network, and rare variant analyses demonstrated the functional significance of candidate genes in healthy and diseased motor neurons and brain tissues. Genetic convergence between common and rare variation highlighted KANK1 as a new ALS gene. Reproducing KANK1 patient mutations in human neurons led to neurotoxicity and demonstrated that TDP-43 mislocalization, a hallmark pathology of ALS, is downstream of axonal dysfunction. RefMap can be readily applied to other complex diseases

Wild-bird trade and exotic invasions: A new link of conservation concern?

Exotic invasions are viewed as a major threat to global biodiversity, but predicting potential invaders is still a difficult task. Here, we highlight a hitherto unnoticed link between the increasing demand for pet birds in developed countries and avian invasions. Paradoxically, it is not the most common caged bird species that seem to be the most successful invaders, but those that are caught in the wild and traded on the pet market. Captive-bred species appear to have lost their ability to return to nature. Thus, the risk of biological invasion in importing countries should inform the current debate over potential bans on the wild-bird trade worldwide. This is a new piece of an already complex puzzle, in which the social, economic, and environmental aspects of both the importing and exporting countries must be weighed before any policy or resource-management measure can be instituted. © The Ecological Society of America.Peer Reviewe

Electrically Pumped Metallo-dielectric Pedestal Nanolasers

Electrically pumped metallo-dielectric nanolasers are demonstrated. Employing a two-step InP chemical etching, we obtain straight pedestal sidewalls and preferentially reduce the diameter of the n-doped InP cladding more than the p-doped one for optimized performance. © 2013 IEEE.DARPA; Defense Advanced Research Projects Agency; NSF; National Science Foundation; ARO; Army Research OfficeDing, K., Ning, C., Metallic subwavelength-cavity semiconductor nanolasers (2012) Light: Science & Applications, 1, pp. e20Nezhad, M.P., Simic, A., Bondarenko, O., Slutsky, B., Mizrahi, A., Feng, L., Lomakin, V., Fainman, Y., Roomtemperature subwavelength metallo-dielectric lasers (2010) Nature Photonics, 4, pp. 395-399Lee, J.H., Khajavikhan, M., Simic, A., Gu, Q., Bondarenko, O., Slutsky, B., Nezhad, M.P., Fainman, Y., Electrically pumped sub-wavelength metallo-dielectric pedestal pillar lasers (2011) Optics Express, 19, pp. 21524-21531Inamura, E., Miyamoto, Y., Tamura, S., Takasugi, T., Furuya, K., Wet chemical etching for ultrafine periodic structure: Rectangular InP corrugations of 70 nm pitch and 100 nm depth (1989) Japanese Journal of Applied Physics, 28, pp. 2193-219

Evolving Services from a Contractual Perspective

International audienceIn an environment of constant change, driven by competitionand innovation, a service can rarely remain stable - especially when it de-pends on other services to fulfill its functionality. However, uncontrolledchanges can easily break the existing relationships between a service andits environment (its customers and providers). In this paper we presentan approach that allows for the controlled evolution of a service by lever-aging the loosely-coupled nature of the SOA paradigm. More specifically,we formalize the notion of contracts between interacting services that en-able their independent evolution and we investigate under which criteriacan changes to a contract-bound service, or even to the contract itself,be transparent to the environment of the service.Keywords: service evolution, service contracts, compatibility, contractinvariance, contract evolutio

Longitudinal changes of ADHD symptoms in association with white matter microstructure: A tract-specific fixel-based analysis

BACKGROUND: Variation in the longitudinal course of childhood attention deficit/hyperactivity disorder (ADHD) coincides with neurodevelopmental maturation of brain structure and function. Prior work has attempted to determine how alterations in white matter (WM) relate to changes in symptom severity, but much of that work has been done in smaller cross-sectional samples using voxel-based analyses. Using standard diffusion-weighted imaging (DWI) methods, we previously showed WM alterations were associated with ADHD symptom remission over time in a longitudinal sample of probands, siblings, and unaffected individuals. Here, we extend this work by further assessing the nature of these changes in WM microstructure by including an additional follow-up measurement (aged 18 - 34 years), and using the more physiologically informative fixel-based analysis (FBA). METHODS: Data were obtained from 139 participants over 3 clinical and 2 follow-up DWI waves, and analyzed using FBA in regions-of-interest based on prior findings. We replicated previously reported significant models and extended them by adding another time-point, testing whether changes in combined ADHD and hyperactivity-impulsivity (HI) continuous symptom scores are associated with fixel metrics at follow-up. RESULTS: Clinical improvement in HI symptoms over time was associated with more fiber density at follow-up in the left corticospinal tract (lCST) (t(max) = 1.092, standardized effect[SE] = 0.044, p(FWE) = 0.016). Improvement in combined ADHD symptoms over time was associated with more fiber cross-section at follow-up in the lCST (t(max) = 3.775, SE = 0.051, p(FWE) = 0.019). CONCLUSIONS: Aberrant white matter development involves both lCST micro- and macrostructural alterations, and its path may be moderated by preceding symptom trajectory

Reduced fronto-striatal volume in attention-deficit/hyperactivity disorder in two cohorts across the lifespan

Attention-Deficit/Hyperactivity Disorder (ADHD) has been associated with altered brain anatomy in neuroimaging studies. However, small and heterogeneous study samples, and the use of region-of-interest and tissue-specific analyses have limited the consistency and replicability of these effects. We used a data-driven multivariate approach to investigate neuroanatomical features associated with ADHD in two independent cohorts: the Dutch NeuroIMAGE cohort (n = 890, 17.2 years) and the Brazilian IMpACT cohort (n = 180, 44.2 years). Using independent component analysis of whole-brain morphometry images, 375 neuroanatomical components were assessed for association with ADHD. In both discovery (corrected-p = 0.0085) and replication (p = 0.032) cohorts, ADHD was associated with reduced volume in frontal lobes, striatum, and their interconnecting white-matter. Current results provide further evidence for the role of the fronto-striatal circuit in ADHD in children, and for the first time show its relevance to ADHD in adults. The fact that the cohorts are from different continents and comprise different age ranges highlights the robustness of the findings