Insulin-like growth factor-1 is a negative modulator of glucagon secretion

Glucagon secretion involves a combination of paracrine, autocrine, hormonal, and autonomic neural mechanisms. Type 2 diabetes often presents impaired glucagon suppression by insulin and glucose. Insulin-like growth factor-I (IGF-1) has elevated homology with insulin, and regulates pancreatic β-cells insulin secretion. Insulin and IGF-1 receptors share considerable structure homology and function. We hypothesized the existence of a mechanism linking the inhibition of α-cells glucagon secretion to IGF-1. Herein, we evaluated the association between plasma IGF-1 and glucagon levels in 116 nondiabetic adults. After adjusting for age gender and BMI, fasting glucagon levels were positively correlated with 2-h post-load glycaemia, HOMA index and fasting insulin, and were negatively correlated with IGF-1 levels. In a multivariable regression, the variables independently associated to fasting glucagon were circulating IGF-1 levels, HOMA index and BMI, explaining 20.7% variation. To unravel the molecular mechanisms beneath IGF-1 and glucagon association, we investigated whether IGF-1 directly modulates glucagon expression and secretion in an in vitro model of α-cells. Our data showed that IGF-1 inhibits the ability of low glucose concentration to stimulate glucagon expression and secretion via activation of the phosphatidylinositol-3-kinase/Akt/FoxO1 pathway. Collectively, our results suggest a new regulatory role of IGF-1 on α-cells biological function

The Effects of Non-Indigenous Macrophytes on Native Biodiversity: Case Studies from Sicily

Biological invasions are widely recognized as a major threat to native biodiversity, ecosys tem functioning and services. Non-indigenous species (NIS) may in time become invasive (invasive alien species (IAS)), determining significant environmental, socioeconomic and human health impacts such as biodiversity loss and ecosystem service degradation. The Mediterranean islands, particu larly Sicily and the circum-Sicilian islands (northwestern Mediterranean Sea), which are important hotspots of biodiversity, are notably vulnerable to anthropogenic pressures such as biological in vasions. Therefore, monitoring NIS distribution as well as understanding their effects on native biodiversity is critical in these areas for planning effective conservation strategies. Here, we report four different case studies from Sicily that highlight how NIS may affect native biodiversity and habitats. The first three case studies were carried out within Marine Protected Areas (MPAs) and highlight (1) the ability of Caulerpa cylindracea to promote the establishment of other NIS, including biofouling worms belonging to the genus Branchiomma; (2) how the shift in habitat from the native Ericaria brachycarpa to the invasive Asparagopsis taxiformis may drastically erode the primary producer biomass and associated biodiversity; and (2) that the presence of Lophocladia lallemandii can affect the molluscan assemblage inhabiting the canopy-forming Gongolaria montagnei. The fourth case study, performed along the northwestern coast of Sicily, shows how Halophila stipulacea can affect the growth of the co-occurring native seagrass Cymodocea nodosa. Overall, these case studies demonstrate various ways in which NIS can interact with native biodiversity and habitats. Furthermore, they emphasize that MPAs are ineffective at preventing the introduction and spread of NIS

Homogeneous Photometry V: The Globular Cluster NGC 4147

New BVRI broad-band photometry and astrometry are presented for the globular cluster NGC 4147, based upon measurements derived from 524 ground-based CCD images mostly either donated by colleagues or retrieved from public archives. We have also reanalysed five exposures of the cluster obtained with WFPC2 on the Hubble Space Telescope in the F439W and F555W (B and V) filters. We present calibrated color-magnitude and color-color diagrams. Analysis of the color-magnitude diagram reveals morphogical properties generally consistent with published metal-abundance estimates for the cluster, and an age typical of other Galactic globular clusters of similar metallicity. We have also redetermined the periods and mean magnitudes for the RR Lyrae variables, including a new c-type variable reported here for the first time. Our data do not show clear evidence for photometric variability in candidate V18, recently reported by Arellano Ferro et al. (2004). These observations also support the non-variable status of candidates V5, V9, and V15. The union of our light-curve data with those of Newburn (1957), Mannino (1957) and Arellano Ferro et al. (op. cit.) permits the derivation of significantly improved periods. The mean periods and the Bailey period-amplitude diagrams support the classification of the cluster as Oosterhoff I despite its predominantly blue horizontal branch. The number ratio of c- to ab-type RR Lyrae stars, on the other hand, is unusually high for an Oosterhoff I cluster. The calibrated results have been made available through the first author's web site.Comment: 30 pages, 30 figures. PASP, in press. Uses 11/2004 version of emulateapj (included). For the full-resolution preprint, the reader is encouraged to download the ps file (123 pages, manuscript format) available at http://cadcwww.hia.nrc.ca/stetson/NGC4147/ms.ps.gz, or the pdf file (30 pages, preprint format) available at http://www.astro.puc.cl/~mcatelan/N4147/full-res.pd

Biogeochemical and Optical Analysis of Coastal DOM for Satellite Retrieval of Terrigenous DOM in the U.S. Middle Atlantic Bight

Estuaries and coastal ocean waters experience a high degree of variability in the composition and concentration of particulate and dissolved organic matter (DOM) as a consequence of riverine/estuarine fluxes of terrigenous DOM, sediments, detritus and nutrients into coastal waters and associated phytoplankton blooms. Our approach integrates biogeochemical measurements (elemental content, molecular analyses), optical properties (absorption) and remote sensing to examine terrestrial DOM contributions into the U.S. Middle Atlantic Bight (MAB). We measured lignin phenol composition, DOC and CDOM absorption within the Chesapeake and Delaware Bay mouths, plumes and adjacent coastal ocean waters to derive empirical relationships between CDOM and biogeochemical measurements for satellite remote sensing application. Lignin ranged from 0.03 to 6.6 ug/L between estuarine and outer shelf waters. Our results demonstrate that satellite-derived CDOM is useful as a tracer of terrigenous DOM in the coastal ocea

Association between serum Mg2+ concentrations and cardiovascular organ damage in a cohort of adult subjects

Magnesium (Mg2+) levels are associated with insulin resistance, hypertension, atherosclerosis, and type 2 diabetes (T2DM). We evaluated the clinical utility of physiological Mg2+ in assessing subclinical cardiovascular organ damage including increased carotid artery intima-media thickness (c-IMT) and left ventricular mass index (LVMI) in a cohort of well-characterized adult non-diabetic individuals. Age-and gender-adjusted correlations between Mg2+ and metabolic parameters showed that Mg2+ circulating levels were correlated negatively with body mass index (BMI), fasting glucose, and 2h-oral glucose tolerance test (OGTT) glucose. Similarly, Mg2+ levels were significantly and negatively related to c-IMT and LVMI. A multivariate regression analysis revealed that age (β = 0.440; p < 0.0001), BMI (β = 0.225; p < 0.0001), and Mg2+ concentration (β = −0.122; p < 0.01) were independently associated with c-IMT. Age (β = 0.244; p = 0.012), Mg2+ (β = −0.177; p = 0.019), and diastolic blood pressure (β = 0.184; p = 0.038) were significantly associated with LVMI in women, while age (β = 0.211; p = 0.019), Mg2+ (β = −0.171; p = 0.038) and the homeostasis model assessment index of insulin resistance (HOMA-IR) (β = −0.211; p = 0.041) were the sole variables associated with LVMI in men. In conclusion, our data support the hypothesis that the assessment of Mg2+ as part of the initial work-up might help unravel the presence of subclinical organ damage in subjects at increased risk of cardiovascular complications

Inverse Classification for Comparison-based Interpretability in Machine Learning

In the context of post-hoc interpretability, this paper addresses the task of explaining the prediction of a classifier, considering the case where no information is available, neither on the classifier itself, nor on the processed data (neither the training nor the test data). It proposes an instance-based approach whose principle consists in determining the minimal changes needed to alter a prediction: given a data point whose classification must be explained, the proposed method consists in identifying a close neighbour classified differently, where the closeness definition integrates a sparsity constraint. This principle is implemented using observation generation in the Growing Spheres algorithm. Experimental results on two datasets illustrate the relevance of the proposed approach that can be used to gain knowledge about the classifier.Comment: preprin

Modeling the Dynamics and Export of Dissolved Organic Matter in the Northeastern U.S. Continental Shelf

Continental shelves are believed to play a major role in carbon cycling due to their high productivity. Particulate organic carbon (POC) burial has been included in models as a carbon sink, but we show here that seasonally produced dissolved organic carbon (DOC) on the shelf can be exported to the open ocean by horizontal transport at similar rates (1-2 mol C/sq m/yr) in the southern U.S. Mid-Atlantic Bight (MAB). The dissolved organic matter (DOM) model imbedded in a coupled circulation-biogeochemical model reveals a double dynamics: the progressive release of dissolved organic nitrogen (DON) in the upper layer during summer increases the regenerated primary production by 30 to 300%, which, in turns ; enhances the DOC production mainly from phytoplankton exudation in the upper layer and solubilization of particulate organic matter (POM) deeper in the water column. This analysis suggests that DOM is a key element for better representing the ecosystem functioning and organic fluxes in models because DOM (1) is a major organic pool directly related to primary production, (2) decouples partially the carbon and nitrogen cycles (through carbon excess uptake, POM solubilization and DOM mineralization) and (3) is intimately linked to the residence time of water masses for its distribution and export

Antiproliferative properties and g-quadruplex-binding of symmetrical naphtho[1,2-b:8,7-b’]dithiophene derivatives

Background: G-quadruplex (G4) forming sequences are recurrent in telomeres and promoter regions of several protooncogenes. In normal cells, the transient arrangements of DNA in G-tetrads may regulate replication, transcription, and translation processes. Tumors are character-ized by uncontrolled cell growth and tissue invasiveness and some of them are possibly mediated by gene expression involving G-quadruplexes. The stabilization of G-quadruplex sequences with small molecules is considered a promising strategy in anticancer targeted therapy. Methods: Molecular virtual screening allowed us identifying novel symmetric bifunctionalized naphtho[1,2-b:8,7-b’]dithiophene ligands as interesting candidates targeting h-Telo and c-MYC G-quadruplexes. A set of unexplored naphtho-dithiophene derivatives has been synthesized and biologically tested through in vitro antiproliferative assays and spectroscopic experiments in solution. Results: The analysis of biological and spectroscopic data highlighted noteworthy cytotoxic effects on HeLa cancer cell line (GI50 in the low µM range), but weak interactions with G-quadruplex c-MYC promoter. Conclusions: The new series of naphtho[1,2-b:8,7-b’]dithiophene derivatives, bearing the pharmacophoric assump-tions necessary to stabilize G-quadruplexes, have been designed and successfully synthesized. The interesting antiproliferative results supported by computer aided rational approaches suggest that these studies are a significant starting point for a lead optimization process and the isolation of a more efficacious set of G-quadruplexes stabilizers

Antiproliferative properties and g-quadruplex-binding of symmetrical naphtho[1,2-b:8,7-b’]dithiophene derivatives

Background: G-quadruplex (G4) forming sequences are recurrent in telomeres and promoter regions of several protooncogenes. In normal cells, the transient arrangements of DNA in G-tetrads may regulate replication, transcription, and translation processes. Tumors are characterized by uncontrolled cell growth and tissue invasiveness and some of them are possibly mediated by gene expression involving G-quadruplexes. The stabilization of G-quadruplex sequences with small molecules is considered a promising strategy in anticancer targeted therapy. Methods: Molecular virtual screening allowed us identifying novel symmetric bifunctionalized naphtho[1,2-b:8,7-b’]dithiophene ligands as interesting candidates targeting h-Telo and c-MYC G-quadruplexes. A set of unexplored naphtho-dithiophene derivatives has been synthesized and biologically tested through in vitro antiproliferative assays and spectroscopic experiments in solution. Results: The analysis of biological and spectroscopic data highlighted noteworthy cytotoxic effects on HeLa cancer cell line (GI(50) in the low μM range), but weak interactions with G-quadruplex c-MYC promoter. Conclusions: The new series of naphtho[1,2-b:8,7-b’]dithiophene derivatives, bearing the pharmacophoric assumptions necessary to stabilize G-quadruplexes, have been designed and successfully synthesized. The interesting antiproliferative results supported by computer aided rational approaches suggest that these studies are a significant starting point for a lead optimization process and the isolation of a more efficacious set of G-quadruplexes stabilizers