Eden Prairie, MN, United States
Eden Prairie, MN, United States
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Paulsen J.,University of Oslo | Sekelja M.,University of Oslo | Oldenburg A.R.,University of Oslo | Barateau A.,University Paris Diderot | And 9 more authors.
Genome Biology | Year: 2017

Current three-dimensional (3D) genome modeling platforms are limited by their inability to account for radial placement of loci in the nucleus. We present Chrom3D, a user-friendly whole-genome 3D computational modeling framework that simulates positions of topologically-associated domains (TADs) relative to each other and to the nuclear periphery. Chrom3D integrates chromosome conformation capture (Hi-C) and lamin-associated domain (LAD) datasets to generate structure ensembles that recapitulate radial distributions of TADs detected in single cells. Chrom3D reveals unexpected spatial features of LAD regulation in cells from patients with a laminopathy-causing lamin mutation. Chrom3D is freely available on github. © 2017 The Author(s).


Kontush A.,French Institute of Health and Medical Research | Kontush A.,University Pierre and Marie Curie | Kontush A.,Pitie Salpetriere University Hospital | Kontush A.,Ican Inc | And 11 more authors.
Handbook of Experimental Pharmacology | Year: 2015

A molecular understanding of high-density lipoprotein (HDL) will allow a more complete grasp of its interactions with key plasma remodelling factors and with cell-surface proteins that mediate HDL assembly and clearance. However, these particles are notoriously heterogeneous in terms of almost every physical, chemical and biological property. Furthermore, HDL particles have not lent themselves to high-resolution structural study through mainstream techniques like nuclear magnetic resonance and X-ray crystallography; investigators have therefore had to use a series of lower resolution methods to derive a general structural understanding of these enigmatic particles. This chapter reviews current knowledge of the composition, structure and heterogeneity of human plasma HDL. The multifaceted composition of the HDL proteome, the multiple major protein isoforms involving translational and posttranslational modifications, the rapidly expanding knowledge of the HDL lipidome, the highly complex world of HDL subclasses and putative models of HDL particle structure are extensively discussed. A brief history of structural studies of both plasma-derived and recombinant forms of HDL is presented with a focus on detailed structural models that have been derived from a range of techniques spanning mass spectrometry to molecular dynamics. © The Author(s) 2015.


Chandon P.,Ican Inc | Wansink B.,Cornell University
Nutrition Reviews | Year: 2012

Food marketing is often singled out as the leading cause of the obesity epidemic. The present review examines current food marketing practices to determine how exactly they may be influencing food intake, and how food marketers could meet their business objectives while helping people eat healthier. Particular attention is paid to the insights provided by recently published studies in the areas of marketing and consumer research, and those insights are integrated with findings from studies in nutrition and related disciplines. The review begins with an examination of the multiple ways in which 1) food pricing strategies and 2) marketing communication (including branding and food claims) bias food consumption. It then describes the effects of newer and less conspicuous marketing actions, focusing on 3) packaging (including the effects of package design and package-based claims) and 4) the eating environment (including the availability, salience, and convenience of food). Throughout, this review underscores the promising opportunities that food manufacturers and retailers have to make profitable "win-win" adjustments to help consumers eat better. © 2012 International Life Sciences Institute.


Camont L.,French Institute of Health and Medical Research | Camont L.,University Pierre and Marie Curie | Camont L.,Groupe Hospitalier Pitie Salpetriere | Camont L.,Ican Inc | And 27 more authors.
Arteriosclerosis, Thrombosis, and Vascular Biology | Year: 2013

OBJECTIVE - : High-density lipoprotein (HDL) displays multiple atheroprotective activities and is highly heterogeneous in structure, composition, and function; the molecular determinants of atheroprotective functions of HDL are incompletely understood. Because phospholipids represent a major bioactive lipid component of HDL, we characterized the phosphosphingolipidome of major normolipidemic HDL subpopulations and related it to HDL functionality. APPROACH AND RESULTS - : Using an original liquid chromatography-mass spectrometry/mass spectrometry methodology for phospholipid and sphingolipid profiling, 162 individual molecular lipid species were quantified across the 9 lipid subclasses, in the order of decreasing abundance, phosphatidylcholine>sphingomyelin>lysophosphatidylcholine> phosphatidylethanolamine>phosphatidylinositol>ceramide> phosphatidylserine>phosphatidylglycerol>phosphatidic acid. When data were expressed relative to total lipid, the contents of lysophosphatidylcholine and of negatively charged phosphatidylserine and phosphatidic acid increased progressively with increase in hydrated density of HDL, whereas the proportions of sphingomyelin and ceramide decreased. Key biological activities of HDL subpopulations, notably cholesterol efflux capacity from human THP-1 macrophages, antioxidative activity toward low-density lipoprotein oxidation, antithrombotic activity in human platelets, cell-free anti-inflammatory activity, and antiapoptotic activity in endothelial cells, were predominantly associated with small, dense, protein-rich HDL3. The biological activities of HDL particles were strongly intercorrelated, exhibiting significant correlations with multiple components of the HDL phosphosphingolipidome. Specifically, the content of phosphatidylserine revealed positive correlations with all metrics of HDL functionality, reflecting enrichment of phosphatidylserine in small, dense HDL3. CONCLUSIONS - : Our structure-function analysis thereby reveals that the HDL lipidome may strongly affect atheroprotective functionality. © 2013 American Heart Association, Inc.


PubMed | French Institute of Health and Medical Research, Ican Inc and University of Patras
Type: Journal Article | Journal: Biochemistry | Year: 2016

In addition to high-density lipoprotein cholesterol (HDL-C) levels, HDL quality also appears to be very important for atheroprotection. Analysis of various clinical paradigms suggests that the lipid and apolipoprotein composition of HDL defines its size, shape, and functions and may determine its beneficial effects on human health. Previously, we reported that like apolipoprotein A-I (Apoa1), apolipoprotein E (Apoe) is also capable of promoting the de novo biogenesis of HDL with the participation of ATP binding cassette A lipid transporter member 1 (Abca1) and plasma enzyme lecithin:cholesterol acyltransferase (Lcat), in a manner independent of a functional Apoa1. Here, we performed a comparative analysis of the functions of these HDL subpopulations. Specifically, Apoe and Apoa1 double-deficient (Apoe(-/-) Apoa1(-/-)) mice were infected with APOA1- or APOE3-expressing adenoviruses, and APOA1-containing HDL (APOA1-HDL) and APOE3-containing HDL (APOE3-HDL), respectively, were isolated and analyzed by biochemical and physicochemical methods. Western blot and lipidomic analyses indicated significant differences in the apolipoprotein and lipid composition of the two HDL species. Moreover APOE3-HDL presented a markedly reduced antioxidant potential and Abcg1-mediated cholesterol efflux capacity. Surprisingly, APOE3-HDL but not APOA1-HDL attenuated LPS-induced production of TNF in RAW264.7 cells, suggesting that the anti-inflammatory effects of APOA1 are dependent on APOE expression. Taken together, our data indicate that APOA1 and APOE3 recruit different apolipoproteins and lipids on the HDL particle, leading to structurally and functionally distinct HDL subpopulations. The distinct role of these two apolipoproteins in the modulation of HDL functionality may pave the way toward the development of novel pharmaceuticals that aim to improve HDL functionality.


PubMed | Hopital University Necker Enfants malades, AP HP, Ican Inc and University Pierre and Marie Curie
Type: | Journal: Clinical endocrinology | Year: 2016

Spontaneous resumption of ovarian function is not a rare phenomenon in patients with premature ovarian insufficiency (POI). The outcome of this resumption is not known.To describe the outcome following the resumption of ovarian function in POI patients.Cross sectional study.University medical centre.Cumulative incidence of ovarian function resumption and risk factors arresting this resumption during follow-up were determined in a large cohort of POI women.Five hundred and seven patients were included in the study, with a follow up of 3.444.05 years [0-29]. Of these, 117 (23%) had features of ovarian function resumption. The cumulative incidence of pregnancy was 3.5% among the whole cohort and 15.3% among patients with resumption of ovarian function. Fifty-five patients (47%) experienced an arrest of their resumption during the follow up period. In univariate analysis, high FSH and DHEA levels at initial evaluation were risk factors for the arrest of the resumption of ovarian function. In multivariate analysis, high FSH levels at the initial evaluation (1.89 [1.10-3.23], p=0.03) and older age at diagnosis (1.53 [1.01-2.33], p=0.04) were risk factors for the arrest of this resumption.Resumption of ovarian function is not a rare or brief phenomenon in POI women. The identification of predictive factors of this resumption, as well as its duration, increases our knowledge of the natural history of POI, and will improve the medical management, especially infertility counselling of these patients. This article protected by copyright. All rights reserved.


PubMed | 3 San Raffaele Research Institute, University of Trieste, Ican Inc, Childrens Hospital of Pittsburgh and University of Pittsburgh
Type: | Journal: The Journal of clinical endocrinology and metabolism | Year: 2016

To assess the frequency of variants, including biallelic pathogenic variants, in MCM8 and MCM9, other genes related to MCM8/9 and DNA damage repair (DDR) pathway in participants with primary ovarian insufficiency (POI).MCM8, MCM9 and genes encoding DDR proteins that have been implicated in reproductive aging were sequenced among POI participants.Academic research institution Participants: All were diagnosed with POI prior to the age of 40 and presented with elevated FSH levels.None Main Outcome Measures: We identified nucleotide variants in MCM8, MCM9, and genes thought to be involved in the DNA damage response pathway and/or implicated in reproductive aging.MCM8 was sequenced in 155 POI participants, while MCM9 was sequenced in 151 participants. Three out of 155 (2%) participants carried possibly damaging heterozygous variants in MCM8, while 7 of 151 (5%) individuals carried possibly damaging heterozygous variants in MCM9. One participant carried a novel homozygous variant, c.1651C>T, p.Gln551* in MCM9 which is predicted to introduce a premature stop codon in exon 9. Biallelic damaging heterozygous variants in both MCM8 and MCM9 were identified in one participant. Out of a total of 10 participants carrying damaging heterozygous variants in either MCM8 or MCM9, two individuals carried heterozygous damaging variants in genes associated with either MCM8-MCM9 or DDR pathway Conclusions: We identified a significant number of potentially damaging and novel variants in MCM8 and MCM9 among participants with POI, and examined multi-allelic association with variants in DDR and MCM8/MCM9 interactome genes.


Trademark
Ican Inc | Date: 2014-06-16

trash receptacles.


Trademark
Ican Inc | Date: 2010-02-03

Geothermal energy generation systems comprising heat exchangers, pumps, heat pumps, piping, and electrical and electronic apparatus and equipment all for use in generating energy obtained from alternative energy sources and replacement parts therefor; Solar energy generation systems comprising solar-powered electricity generators and motors, gears, drives for orientating solar panels, and electrical and electronic apparatus and equipment all for use in generating energy obtained from alternative energy sources and replacement parts therefor; Wind energy generation systems comprising wind-powered electricity generators, wind turbines, generators for wind turbines, propellers for wind-powered electricity generators, and electrical and electronic apparatus and equipment all for use in generating energy obtained from alternative energy sources and replacement parts therefor; structural components and replacement parts for each of the foregoing, namely, wind power turbines. Consulting services in the fields of energy usage management and conservation; Management and operations assistance for energy generation and co-generation systems, including geothermal energy systems, solar energy systems and wind energy systems. Consulting in the areas of energy distribution. Consulting services in the areas of energy production, generation, co-generation, and treatment of electrical energy for others. Inspection of facilities and plants for energy production, generation, co-generation, distribution, transportation, transmission, storage and treatment of electrical energy; Remote monitoring of facilities and plants for energy production, generation, co-generation, distribution, transportation, transmission, storage and treatment of electrical energy for others; Architectural and engineering services in the area of energy generation and co-generation systems, including geothermal energy systems, solar energy systems, wind energy systems, and components therefor.


Trademark
Ican Inc | Date: 2010-02-22

Geothermal energy generation systems comprising heat exchangers, pumps, heat pumps, piping, and electrical and electronic apparatus and equipment all for use in generating energy obtained from alternative energy sources and replacement parts therefor; Solar energy generation systems comprising solar-powered electricity generators and motors, gears, drives for orientating solar panels, and electrical and electronic apparatus and equipment all for use in generating energy obtained from alternative energy sources and replacement parts therefor; Wind energy generation systems comprising wind-powered electricity generators, wind turbines, generators for wind turbines, propellers for wind-powered electricity generators, and electrical and electronic apparatus and equipment all for use in generating energy obtained from alternative energy sources and replacement parts therefor; structural components and replacement parts for each of the foregoing, namely, wind power turbines. Consulting services in the fields of energy usage management and conservation; Management and operations assistance for energy generation and co-generation systems, including geothermal energy systems, solar energy systems and wind energy systems. Consulting in the areas of energy distribution. Consulting services in the areas of energy production, generation, co-generation and treatment of electrical energy for others. Inspection of facilities and plants for energy production, generation, co-generation, distribution, transportation, transmission, storage and treatment of electrical energy; Remote monitoring of facilities and plants for energy production, generation, co-generation, distribution, transportation, transmission, storage and treatment of electrical energy for others; Architectural and engineering services in the area of energy generation and co-generation systems, including geothermal energy systems, solar energy systems, wind energy systems, and components therefor.

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