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https://www.readbyqxmd.com/read/29742964/efficient-generation-of-cynomolgus-monkey-induced-pluripotent-stem-cell-derived-intestinal-organoids-with-pharmacokinetic-functions
#1
Daichi Onozato, Misaki Yamashita, Ryosuke Fukuyama, Takumi Akagawa, Yuriko Kida, Akiko Koeda, Tadahiro Hashita, Takahiro Iwao, Tamihide Matsunaga
In preclinical studies, the cynomolgus monkey (CM) model is frequently used to predict the pharmacokinetics of drugs in the human small intestine, because of its evolutionary closeness to humans. Intestinal organoids that mimic the intestinal tissue have attracted attention in regenerative medicine and drug development. In this study, we generated intestinal organoids from CM induced pluripotent stem (CMiPS) cells and analysed their pharmacokinetic functions. CMiPS cells were induced into the hindgut; then, the cells were seeded on microfabricated culture vessel plates to form spheroids...
May 10, 2018: Stem Cells and Development
https://www.readbyqxmd.com/read/29736343/comparing-cmip-3-and-cmip-5-climate-projections-on-flooding-estimation-of-devils-lake-of-north-dakota-usa
#2
Gehendra Kharel, Andrei Kirilenko
Background: Water level fluctuations in endorheic lakes are highly susceptible to even slight changes in climate and land use. Devils Lake (DL) in North Dakota, USA is an endorheic system that has undergone multi-decade flooding driven by changes in regional climate. Flooding mitigation strategies have centered on the release of lake water to a nearby river system through artificial outlets, resulting in legal challenges and environmental concerns related to water quality, downstream flooding, species migration, stakeholder opposition, and transboundary water conflicts between the US and Canada...
2018: PeerJ
https://www.readbyqxmd.com/read/29699034/-association-between-obesity-and-dna-methylation-among-the-7-16-year-old-twins
#3
C X Li, Y Gao, W J Gao, C Q Yu, J Lyu, R R Lyu, J L Duan, Y Sun, X H Guo, S F Wang, B Zhou, G Wang, W H Cao, L M Li
Objective: On whole-genome scale, we tried to explore the correlation between obesity-related traits and DNA methylation sites, based on discordant monozygotic twin pairs. Methods: A total of 90 pairs of 6-17 year-old twins were recruited in Chaoyang district, Yanqing district and Fangshan district in Beijing in 2016. Information on twins was gathered through a self-designed questionnaire and results: from physical examination, including height, weight and waist circumference of the subjects under study. DNA methylation detection was chosen on the Illumina Human Methylation EPIC BeadChip...
April 10, 2018: Zhonghua Liu Xing Bing Xue za Zhi, Zhonghua Liuxingbingxue Zazhi
https://www.readbyqxmd.com/read/29691896/genome-wide-interaction-with-the-insulin-secretion-locus-mtnr1b-reveals-cmip-as-a-novel-type-2-diabetes-susceptibility-gene-in-african-americans
#4
Jacob M Keaton, Chuan Gao, Meijian Guan, Jacklyn N Hellwege, Nicholette D Palmer, James S Pankow, Myriam Fornage, James G Wilson, Adolfo Correa, Laura J Rasmussen-Torvik, Jerome I Rotter, Yii-Der I Chen, Kent D Taylor, Stephen S Rich, Lynne E Wagenknecht, Barry I Freedman, Maggie C Y Ng, Donald W Bowden
Although type 2 diabetes (T2D) results from metabolic defects in insulin secretion and insulin sensitivity, most of the genetic risk loci identified to date relates to insulin secretion. We reported that T2D loci influencing insulin sensitivity may be identified through interactions with insulin secretion loci, thereby leading to T2D. Here, we hypothesize that joint testing of variant main effects and interaction effects with an insulin secretion locus increases power to identify genetic interactions leading to T2D...
April 24, 2018: Genetic Epidemiology
https://www.readbyqxmd.com/read/29597287/opposite-genetic-effects-of-cmip-polymorphisms-on-the-risk-of-type-2-diabetes-and-obesity-a-family-based-study-in-china
#5
Yaying Cao, Tao Wang, Yiqun Wu, Juan Juan, Xueying Qin, Xun Tang, Tao Wu, Yonghua Hu
C-Maf Inducing Protein ( CMIP ) gene polymorphisms were reported to be associated with type 2 diabetes mellitus (T2DM). Whether the association between CMIP and T2DM is mediated via obesity-related phenotypes is still unclear. We analyzed the association of CMIP rs2925979 with T2DM and a comprehensive set of obesity-related phenotypes in 1576 families ascertained from a Chinese population. These families included a total of 3444 siblings (1582 with T2DM, 963 with prediabetes, and 899 with a normal glucose level)...
March 28, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29398736/inflated-uncertainty-in-multimodel-based-regional-climate-projections
#6
Marianne Sloth Madsen, Peter L Langen, Fredrik Boberg, Jens Hesselbjerg Christensen
Multimodel ensembles are widely analyzed to estimate the range of future regional climate change projections. For an ensemble of climate models, the result is often portrayed by showing maps of the geographical distribution of the multimodel mean results and associated uncertainties represented by model spread at the grid point scale. Here we use a set of CMIP5 models to show that presenting statistics this way results in an overestimation of the projected range leading to physically implausible patterns of change on global but also on regional scales...
November 28, 2017: Geophysical Research Letters
https://www.readbyqxmd.com/read/29056249/nephrutix-a-randomized-double-blind-placebo-vs-rituximab-controlled-trial-assessing-t-cell-subset-changes-in-minimal-change-nephrotic-syndrome
#7
Ahmed Boumediene, Pauline Vachin, Kelhia Sendeyo, Julie Oniszczuk, Shao-Yu Zhang, Carole Henique, Andre Pawlak, Vincent Audard, Mario Ollero, Vincent Guigonis, Djillali Sahali
Minimal-change nephrotic syndrome (MCNS) is an immune-mediated glomerular disease. We have analyzed the modifications on T-cell subsets in twenty-three patients who were highly steroid/calcineurin inhibitor and/or mycophenolate mofetil-dependent for frequently relapsing nephrotic syndrome (FRNS) and who were enrolled in a multicenter, double-blind, randomized, placebo vs Rituximab-controlled trial. Patients with FRNS entered the trial at remission and were randomly assigned to receive either Rituximab or placebo...
March 2018: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28944848/cmip-is-oncogenic-in-human-gastric-cancer-cells
#8
Jianlin Zhang, Jin Huang, Xingyu Wang, Weidong Chen, Qinqing Tang, Maoyong Fang, Yeben Qian
Gastric cancer is one of the most common cancers and the second leading cause of cancer‑associated mortality worldwide. Recurrence, metastasis and resistance to drug treatment are the main barrier to survival of patients with advanced stage gastric cancer. Further study of the molecular mechanisms involved will improve the therapeutic options for gastric cancer. In a previous study, c‑Maf was discovered as an oncogene transduced in the avian AS42 retrovirus, and was found to be overexpressed in multiple myeloma and angioimmunoblastic T‑cell lymphoma...
November 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28791377/c%C3%A2-maf-inducing-protein-inhibits-cofilin%C3%A2-1-activity-and-alters-podocyte-cytoskeleton-organization
#9
Lixia Yu, Jianming Ye, Qifeng Liu, Jianhua Feng, Xiaoxia Gu, Qiang Sun, Guoyuan Lu
The glomerular visceral epithelial cells, also termed podocytes, are key in maintaining the normal renal filtration barrier. Although it has been demonstrated that stimulation of c‑Maf inducing protein (CMIP) expression is involved in podocyte damage, the molecular events during this process remain unclear. In the current study, CMIP‑induced proximal signaling was investigated by focusing on its effect on cofilin‑1 activity in puromycin aminonucleoside (PA)‑damaged podocytes. An obvious elevation of CMIP expression and phosphorylated (p) cofilin‑1 levels was detected in cultured podocytes treated with PA and in glomeruli isolated from PA‑induced nephropathy rats...
October 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28504353/cmip-haploinsufficiency-in-two-patients-with-autism-spectrum-disorder-and-co-occurring-gastrointestinal-issues
#10
Minjie Luo, Jinbo Fan, Tara L Wenger, Margaret H Harr, Melissa Racobaldo, Surabhi Mulchandani, Holly Dubbs, Elaine H Zackai, Nancy B Spinner, Laura K Conlin
Autism spectrum disorder (ASD) is a genetically heterogeneous group of disorders characterized by impairments in social communication and restricted interests. Though some patients with ASD have an identifiable genetic cause, the cause of most ASD remains elusive. Many ASD susceptibility loci have been identified through clinical studies. We report two patients with syndromic ASD and persistent gastrointestinal issues who carry de novo deletions involving the CMIP gene detected by genome-wide SNP microarray and fluorescence in situ hybridization (FISH) analysis...
August 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28155637/cmip-a-software-package-capable-of-reconstructing-genome-wide-regulatory-networks-using-gene-expression-data
#11
Guangyong Zheng, Yaochen Xu, Xiujun Zhang, Zhi-Ping Liu, Zhuo Wang, Luonan Chen, Xin-Guang Zhu
BACKGROUND: A gene regulatory network (GRN) represents interactions of genes inside a cell or tissue, in which vertexes and edges stand for genes and their regulatory interactions respectively. Reconstruction of gene regulatory networks, in particular, genome-scale networks, is essential for comparative exploration of different species and mechanistic investigation of biological processes. Currently, most of network inference methods are computationally intensive, which are usually effective for small-scale tasks (e...
December 23, 2016: BMC Bioinformatics
https://www.readbyqxmd.com/read/28131026/preparation-and-characterization-of-ph-responsive-polyacrylamide-molecularly-imprinted-polymer-application-to-isolation-of-recombinant-and-wild-type-human-serum-albumin-from-biological-sources
#12
May A Abd El-Aal, Medhat A Al-Ghobashy, Faten Abdel Aziz Fathalla, Yasser S El-Saharty
In this work pH-responsive neutral and cationic polyacrylamide molecularly imprinted polymers (nMIP and cMIP, respectively) were prepared for separation of recombinant and wild type human serum albumin (HSA, pI 4.7) using mixture of polymerization initiators. The effect of pH during preparation and adsorption stages at pI(HSA) ±2.0 on binding capacity and selectivity; imprinting factor (IF) was thoroughly investigated. SE-HPLC and RP-HPLC were employed for thorough evaluation of the stability of HSA at the studied experimental conditions and for simultaneous determination of HSA and erythropoietin (EPO) in their mixtures, respectively...
March 1, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28062490/dna-methylation-and-high-density-lipoprotein-functionality-brief-report-the-regicor-study-registre-gironi-del-cor
#13
Sergi Sayols-Baixeras, Alvaro Hernáez, Issac Subirana, Carla Lluis-Ganella, Daniel Muñoz, Montserrat Fitó, Jaume Marrugat, Roberto Elosua
OBJECTIVE: The function of high-density lipoproteins (HDLs) may better reflect their atheroprotective role, compared with HDL-cholesterol levels. The association between DNA methylation and HDL function has not yet been established. APPROACH AND RESULTS: We designed an epigenome-wide association study including 645 individuals from the REGICOR study (Registre Gironi del Cor). We determined DNA methylation from peripheral blood cells using the HumanMethylation450 array...
March 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28011936/the-mhc-class-ii-immunopeptidome-of-lymph-nodes-in-health-and-in-chemically-induced-colitis
#14
Tim Fugmann, Adriana Sofron, Danilo Ritz, Franziska Bootz, Dario Neri
We recently described a mass spectrometry-based methodology that enables the confident identification of hundreds of peptides bound to murine MHC class II (MHCII) molecules. In this article, we describe its application to the characterization of MHCII-bound peptides isolated from lymph nodes (LNs) of C57BL/6 mice. More than 1000 peptides could be identified in individual analyses, allowing a direct comparison of the MHCII peptidome in different types of normal LNs or in animals with colitis. The peptide length distribution and consensus sequences in axillary, brachial, inguinal, and mesenteric LNs were virtually identical, and a substantial portion of identified peptides corresponded to proteins found in all LNs...
February 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28000910/-environmental-and-genetic-variables-related-with-alterations-in-language-acquisition-in-early-childhood
#15
REVIEW
A Moriano-Gutierrez, J Colomer-Revuelta, J Sanjuan, J M Carot-Sierra
INTRODUCTION: A great deal of research has addressed problems in the correct acquisition of language, but with few overall conclusions. The reasons for this lie in the individual variability, the existence of different measures for assessing language and the fact that a complex network of genetic and environmental factors are involved in its development. AIM: To review the environmental and genetic variables that have been studied to date, in order to gain a better under-standing of the causes of specific language impairment and create new evidence that can help in the development of screening systems for the early detection of these disorders...
January 1, 2017: Revista de Neurologia
https://www.readbyqxmd.com/read/27934933/decadal-shifts-of-east-asian-summer-monsoon-in-a-climate-model-free-of-explicit-ghgs-and-aerosols
#16
Renping Lin, Jiang Zhu, Fei Zheng
The East Asian summer monsoon (EASM) experienced decadal transitions over the past few decades, and the associated "wetter-South-drier-North" shifts in rainfall patterns in China significantly affected the social and economic development in China. Two viewpoints stand out to explain these decadal shifts, regarding the shifts either a result of internal variability of climate system or that of external forcings (e.g. greenhouse gases (GHGs) and anthropogenic aerosols). However, most climate models, for example, the Atmospheric Model Intercomparison Project (AMIP)-type simulations and the Coupled Model Intercomparison Project (CMIP)-type simulations, fail to simulate the variation patterns, leaving the mechanisms responsible for these shifts still open to dispute...
December 9, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27885729/new-biosourced-chiral-molecularly-imprinted-polymer-synthesis-characterization-and-evaluation-of-the-recognition-capacity-of-methyltestosterone
#17
Asma Saadaoui, Corinne Sanglar, Raouf Medimagh, Anne Bonhomme, Robert Baudot, Saber Chatti, Sylvain Marque, Damien Prim, Mongia Saïd Zina, Herve Casabianca
New biosourced chiral cross-linkers were reported for the first time in the synthesis of methyltestosterone (MT) chiral molecularly imprinted polymers (cMIPs). Isosorbide and isomannide, known as 1,4:3,6-dianhydrohexitols, were selected as starting diols. The cMIPs were synthesized following a noncovalent approach via thermal radical polymerization and monitored by Raman spectroscopy. These cross-linkers were fully characterized by (1) H and (13) C nuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectrometry...
April 2017: Journal of Molecular Recognition: JMR
https://www.readbyqxmd.com/read/27650733/repression-of-cmip-transcription-by-wt1-is-relevant-to-podocyte-health
#18
Anissa Moktefi, Shao-Yu Zhang, Pauline Vachin, Virginie Ory, Carole Henique, Vincent Audard, Catherine Rucker-Martin, Elodie Gouadon, Michael Eccles, Andreas Schedl, Laurence Heidet, Mario Ollero, Djillali Sahali, Andre Pawlak
The WT1 (Wilm's tumor suppressor) gene is expressed throughout life in podocytes and is essential for the functional integrity of the glomerular filtration barrier. We have previously shown that CMIP (C-Maf inducing protein) is overproduced in podocyte diseases and alters intracellular signaling. Here we isolated the proximal region of the human CMIP promoter and showed by chromatin immunoprecipitation assays and electrophoretic-mobility shift that Wilm's tumor protein (WT1) bound to 2 WT1 response elements, located at positions -290/-274 and -57/-41 relative to transcription start site...
December 2016: Kidney International
https://www.readbyqxmd.com/read/27104953/effects-of-genetic-loci-associated-with-central-obesity-on-adipocyte-lipolysis
#19
Rona J Strawbridge, Helmut Laumen, Anders Hamsten, Michaela Breier, Harald Grallert, Hans Hauner, Peter Arner, Ingrid Dahlman
OBJECTIVES: Numerous genetic loci have been associated with measures of central fat accumulation, such as waist-to-hip ratio adjusted for body mass index (WHRadjBMI). However the mechanisms by which genetic variations influence obesity remain largely elusive. Lipolysis is a key process for regulation of lipid storage in adipocytes, thus is implicated in obesity and its metabolic complications. Here, genetic variants at 36 WHRadjBMI-associated loci were examined for their influence on abdominal subcutaneous adipocyte lipolysis...
2016: PloS One
https://www.readbyqxmd.com/read/26590301/novel-working-hypothesis-for-pathogenesis-of-hematological-malignancies-combination-of-mutations-induced-cellular-phenotypes-determines-the-disease-cmip-dd
#20
REVIEW
Toshio Kitamura, Naoko Watanabe-Okochi, Yutaka Enomoto, Fumio Nakahara, Toshihiko Oki, Yukiko Komeno, Naoko Kato, Noriko Doki, Tomoyuki Uchida, Yuki Kagiyama, Katsuhiro Togami, Kimihito C Kawabata, Koutarou Nishimura, Yasutaka Hayashi, Reina Nagase, Makoto Saika, Tsuyoshi Fukushima, Shuhei Asada, Takeshi Fujino, Yuto Izawa, Sayuri Horikawa, Tomofusa Fukuyama, Yosuke Tanaka, Ryoichi Ono, Susumu Goyama, Tetsuya Nosaka, Jiro Kitaura, Daichi Inoue
Recent progress in high-speed sequencing technology has revealed that tumors harbor novel mutations in a variety of genes including those for molecules involved in epigenetics and splicing, some of which were not categorized to previously thought malignancy-related genes. However, despite thorough identification of mutations in solid tumors and hematological malignancies, how these mutations induce cell transformation still remains elusive. In addition, each tumor usually contains multiple mutations or sometimes consists of multiple clones, which makes functional analysis difficult...
January 2016: Journal of Biochemistry
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