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Yuki Haga, Motoharu Suzuki, Chisato Matsumura, Toshihiro Okuno, Masahiro Tsurukawa, Kazuo Fujimori, Narayanan Kannan, Roland Weber, Takeshi Nakano
In this study, we analyzed hydroxylated polychlorinated biphenyls (OH-PCBs) in urine of both PCB transport workers and PCB researchers. A method to monitor OH-PCB in urine was developed. Urine was solid-phase extracted with 0.1% ammonia/ methanol (v/v) and glucuronic acid/sulfate conjugates and then decomposed using β-glucuronidase/arylsulfatase. After alkaline digestion/derivatization, the concentration of OH-PCBs was determined by HRGC/HRMS-SIM. In the first sampling campaign, the worker's OH-PCB levels increased several fold after the PCB waste transportation work, indicating exposure to PCBs...
April 14, 2018: Environmental Science and Pollution Research International
Hui-Hua Chang, Aune Moro, Caroline Ei Ne Chou, David W Dawson, Samuel French, Andrea I Schmidt, James Sinnett-Smith, Fang Hao, O Joe Hines, Guido Eibl, Enrique Rozengurt
Pancreatic ductal adenocarcinoma (PDAC) is a particularly deadly disease. Chronic conditions, including obesity and type-2 diabetes are risk factors, thus making PDAC amenable to preventive strategies. We aimed to characterize the chemo-preventive effects of metformin, a widely used anti-diabetic drug, on PDAC development using the KrasG12D mouse model subjected to a diet high in fats and calories (HFCD). LSL-KrasG12D/+ ;p48-Cre (KC) mice were given control diet (CD), HFCD, or HFCD with 5 mg/ml metformin in drinking water for 3 or 9 months...
April 12, 2018: Scientific Reports
Florent Morfoisse, Florence Tatin, Benoit Chapût, Nicole Therville, Charlotte Vaysse, Raphael Métivier, Julie Malloizel-Delaunay, Francoise Pujol, Anne-Claire Godet, Fabienne De Toni, Frederic Boudou, Katia Grenier, David Dubuc, Eric Lacazette, Anne-Catherine Prats, Julie Guillermet-Guibert, Francoise Lenfant, Barbara Garmy-Susini
OBJECTIVE: Estrogens exert beneficial effect on the blood vascular system. However, their role on the lymphatic system has been poorly investigated. We studied the protective effect of the 17β estradiol-the most potent endogenous estrogen-in lymphedema-a lymphatic dysfunction, which results in a massive fluid and fat accumulation in the limb. APPROACH AND RESULTS: Screening of DNA motifs able to mobilize ERs (estrogen receptors) and quantitative real-time polymerase chain reaction analysis revealed that estradiol promotes transcriptional activation of lymphangiogenesis-related gene expression including VEGF (vascular endothelial growth factor)-D, VEGFR (VEGF receptor)-3, lyve-1, and HASs (hyaluronan synthases)...
April 12, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
I Vidovic-Zdrilic, K H Vining, A Vijaykumar, I Kalajzic, D J Mooney, M Mina
The goal of this study was to examine the effects of early and limited exposure of perivascular cells expressing α (αSMA) to fibroblast growth factor 2 (FGF2) in vivo. We performed in vivo fate mapping by inducible Cre-loxP and experimental pulp injury in molars to induce reparative dentinogenesis. Our results demonstrate that early delivery of exogenous FGF2 to exposed pulp led to proliferative expansion of αSMA-tdTomato+ cells and their accelerated differentiation into odontoblasts. In vivo lineage-tracing experiments showed that the calcified bridge/reparative dentin in FGF2-treated pulps were lined with an increased number of Dspp+ odontoblasts and devoid of BSP+ osteoblasts...
April 1, 2018: Journal of Dental Research
Chunlin Zuo, Lijun Wang, Raghavendra M Kamalesh, Margot E Bowen, Douglas C Moore, Mark S Dooner, Anthony M Reginato, Qian Wu, Christoph Schorl, Yueming Song, Matthew L Warman, Benjamin G Neel, Michael G Ehrlich, Wentian Yang
Chondrocytes and osteoblasts differentiate from a common mesenchymal precursor, the osteochondroprogenitor (OCP), and help build the vertebrate skeleton. The signaling pathways that control lineage commitment for OCPs are incompletely understood. We asked whether the ubiquitously expressed protein-tyrosine phosphatase SHP2 (encoded by Ptpn11 ) affects skeletal lineage commitment by conditionally deleting Ptpn11 in mouse limb and head mesenchyme using "Cre-loxP"-mediated gene excision. SHP2-deficient mice have increased cartilage mass and deficient ossification, suggesting that SHP2-deficient OCPs become chondrocytes and not osteoblasts...
2018: Bone Research
Natalie Eva Nieuwenhuizen, Frank Kirstein, Jennifer Claire Hoving, Frank Brombacher
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
April 11, 2018: Scientific Reports
He-Jing Bao, Shu-Dong Ma
OBJECTIVE: To investigate the regulatory role of classical Shh signaling pathway in the development of the epithelium and mesenchyme (bronchial cartilage and smooth muscles) during lung development in fetal mice. METHODS: Immunohistochemical technique was used to detect the expression of Shh signaling pathway receptor Smo and Pdgfr-α in murine fetal lungs to explore the spatial and temporal characteristics of their expression. Based on the interstitial specificity of Pdgfr-α expression, we constructed a Pdgfr-α-cre to establish a E12...
March 20, 2018: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
Darren Chern Jan Wong, Li Zhang, Isabelle Merlin, Simone D Castellarin, Gregory A Gambetta
BACKGROUND: The major intrinsic protein (MIP) family is a family of proteins, including aquaporins, which facilitate water and small molecule transport across plasma membranes. In plants, MIPs function in a huge variety of processes including water transport, growth, stress response, and fruit development. In this study, we characterize the structure and transcriptional regulation of the MIP family in grapevine, describing the putative genome duplication events leading to the family structure and characterizing the family's tissue and developmental specific expression patterns across numerous preexisting microarray and RNAseq datasets...
April 11, 2018: BMC Genomics
Yuichi Tamura, Carole Phan, Ly Tu, Morane Le Hiress, Raphaël Thuillet, Etienne-Marie Jutant, Elie Fadel, Laurent Savale, Alice Huertas, Marc Humbert, Christophe Guignabert
Pulmonary arterial hypertension (PAH) is characterized by a progressive accumulation of pulmonary artery smooth muscle cells (PA-SMCs) in pulmonary arterioles leading to the narrowing of the lumen, right heart failure, and death. Although most studies have supported the notion of a role for IL-6/glycoprotein 130 (gp130) signaling in PAH, it remains unclear how this signaling pathway determines the progression of the disease. Here, we identify ectopic upregulation of membrane-bound IL-6 receptor (IL6R) on PA-SMCs in PAH patients and in rodent models of pulmonary hypertension (PH) and demonstrate its key role for PA-SMC accumulation in vitro and in vivo...
April 9, 2018: Journal of Clinical Investigation
Archana Iyer, Lakshmi Subramanian, Shubha Tole
This protocol describes the technique of ex-vivo electroporation to target embryonic hippocampal progenitors in an organotypic slice preparation. This technique allows gene perturbation for examining developmental processes in the embryonic hippocampus while retaining the environment and connectivity of the cells. Gene perturbation can include Cre-mediated recombination, RNAi-mediated knockdown, gene overexpression, or a combination of any of these. Ex-vivo electroporation can be performed at a wide range of embryonic stages, giving temporal control to the experimenter...
March 20, 2018: Bio-protocol
Shaohua Fan, Yanyan Wang, Cun Wang, Haojie Jin, Zheng Wu, Jun Lu, Zifeng Zhang, Chunhui Sun, Qun Shan, Dongmei Wu, Juan Zhuang, Ning Sheng, Ying Xie, Mengqiu Li, Bin Hu, Jingyuan Fang, Yuanlin Zheng, Wenxin Qin
Homo sapienslongevity assurance homolog 2 of yeast LAG1 (LASS2) is expressed mostly in human liver. Here, we explored roles of LASS2 in pathogenesis of hepatic steatosis. Hepatocyte-specific LASS2 knockout (LASS2-/- ) mice were generated using Cre-LoxP system. LASS2-/- and wild-type (WT) mice were fed with chow or high-fat diet (HFD). We found LASS2-/- mice were resistant to HFD-induced hepatic steatosis and insulin resistance. In HFD-fed mice, LASS2 deficiency significantly inhibited p38 MAPK and ERK1/ERK2 signaling in mouse liver...
April 4, 2018: Free Radical Biology & Medicine
Jinhu Xiong, Maria Almeida, Charles A O'Brien
The related transcriptional co-factors YAP (Yes-associated protein) and TAZ (transcriptional co-activator with PDZ-binding motif) have been proposed to either promote or inhibit osteoblast differentiation. Here we investigated the skeletal consequences of deleting YAP and TAZ at different stages of the osteoblast lineage using Prx1-Cre, Osx1-Cre, and Dmp1-Cre transgenic mice. Prx1-Cre-mediated deletion resulted in embryonic lethality. Mice lacking both copies of TAZ and one copy of YAP in cells targeted by Prx1-Cre were viable and displayed elevated bone mass associated increased bone formation...
April 4, 2018: Bone
Mikiko Ikehata, Atsushi Yamada, Koji Fujita, Yuko Yoshida, Tadashi Kato, Akiko Sakashita, Hiroaki Ogata, Takehiko Iijima, Masahiko Kuroda, Daichi Chikazu, Ryutaro Kamijo
Rac1 and Cdc42, Rho family low molecular weight G proteins, are intracellular signaling factors that transmit various information from outside to inside cells. Primarily, they are known to control various biological activities mediated by actin cytoskeleton reorganization, such as cell proliferation, differentiation, and apoptosis. In order to investigate the functions of Rac1 and Cdc42 in bone formation, we prepared cartilage-specific double conditional knockout mice, Rac1fl/fl ; Cdc42fl/fl ; Col2-Cre (Rac1: Cdc42 dcKO mice), which died just after birth, similar to Cdc42fl/fl ; Col2-Cre mice (Cdc42 cKO mice)...
April 4, 2018: Biochemical and Biophysical Research Communications
Katarina Špiranec, Wen Chen, Franziska Werner, Viacheslav O Nikolaev, Takashi Naruke, Franziska Koch, Andrea Werner, Petra Eder-Negrin, Rodrigo Diéguez-Hurtado, Ralf H Adams, Hideo A Baba, Hannes Schmidt, Kai Schuh, Boris V Skryabin, Kiavash Movahedi, Frank Schweda, Michaela Kuhn
Background -Peripheral vascular resistance has a major impact on arterial blood pressure levels. Endothelial C-type natriuretic peptide (CNP) participates in the local regulation of vascular tone but the target cells remain controversial. The cGMP-producing guanylyl cyclase-B (GC-B) receptor for CNP is expressed in vascular smooth muscle cells (VSMC). However, whereas endothelial cell-specific CNP knockout mice are hypertensive, mice with deletion of GC-B in VSMC have unaltered blood pressure. Methods -We analyzed whether the vasodilating response to CNP changes along the vascular tree, i...
April 6, 2018: Circulation
Rui Liu, Ashleigh King, Philippe Bouillet, David M Tarlinton, Andreas Strasser, Jörg Heierhorst
The proapoptotic BH3-only protein BIM ( Bcl2l11 ) plays key roles in the maintenance of multiple hematopoietic cell types. In mice, germline knockout or conditional pan-hematopoietic deletion of Bim results in marked splenomegaly and significantly increased numbers of B cells. However, it has remained unclear whether these abnormalities reflect the loss of cell-intrinsic functions of BIM within the B lymphoid lineage and, if so, which stages in the lifecycle of B cells are most impacted by the loss of BIM. Here, we show that B lymphoid-specific conditional deletion of Bim during early development (i...
2018: Frontiers in Immunology
Zaineb Hamzaoui, Alain Ocampo-Sosa, Marta Fernandez Martinez, Sarrah Landolsi, Sana Ferjani, Elaa Maamar, Mabrouka Saidani, Amine Slim, Luis Martinez-Martinez, Ilhem Boutiba-Ben Boubaker
In K. pneumoniae, the loss of the two major outer membrane porins (OMPs) OmpK35 and OmpK36 confers resistance to carbapenem in strains producing extended spectrum β-lactamases or plasmid-mediated AmpC-type β-lactamases. At Charles Nicolle hospital of Tunis, all carbapenem-resistant Enterobacteriaceae (CRE) were collected over a 6-year period. The aim of this work was to investigate the mechanisms responsible for carbapenem resistance in non-carbapenemase-producing K. pneumoniae (NCPK) strains. Among the 334 CRE collected strains between 2010 and 2015, 44 (13...
April 2, 2018: International Journal of Antimicrobial Agents
Mikako Kawashima, Koichiro Taguchi, Yoshihiko Kitada, Masahiro Yamauchi, Takahide Ikeda, Kazuo Kajita, Daisuke Murakami, Hideyuki Okada, Yoshihiro Uno, Ichiro Mori, Tatsuo Ishizuka, Hiroyuki Morita
AIMS: We have developed and validated a novel scoring system to predict insulin requirement for optimal control of blood glucose during glucocorticoid (GC) treatments, by retrospective analyses of clinical parameters before GC treatment. METHODS: Three hundred-three adults (the Developing set) undergoing their first treatment of prednisolone (PSL) were divided into two groups, depending on treatment with or without insulin. Independent risk factors for insulin requirement were identified by a stepwise logistic regression analysis after univariate analyses between the two groups...
April 3, 2018: Diabetes Research and Clinical Practice
Xiao-Yan Cao, Xiao-Xin Zhang, Min-Wei Yang, Li-Peng Hu, Shu-Heng Jiang, Guang-Ang Tian, Li-Li Zhu, Qing Li, Yong-Wei Sun, Zhi-Gang Zhang
Pancreatic Ductal Adenocarcinoma (PADC) metastasis is the leading cause of morality of this severe malignant tumor. Proteases are key players in the degradation of extracellular matrix which promotes the cascade of tumor metastasis. As a kind of serine proteases, the kallikrein family performs vital function on the cancer proteolysis scene, which have been proved in diverse malignant tumors. However, the specific member of kallikrein family and its function in PDAC remain unexplored. In this study, by data mining of GEO datasets, we have identified KLK10 is upregulated gene in PDAC...
April 2, 2018: Biochemical and Biophysical Research Communications
Kate Russell Woodworth, Maroya Spalding Walters, Lindsey M Weiner, Jonathan Edwards, Allison C Brown, Jennifer Y Huang, Sarah Malik, Rachel B Slayton, Prabasaj Paul, Catherine Capers, Marion A Kainer, Nancy Wilde, Alicia Shugart, Garrett Mahon, Alexander J Kallen, Jean Patel, L Clifford McDonald, Arjun Srinivasan, Michael Craig, Denise M Cardo
BACKGROUND: Approaches to controlling emerging antibiotic resistance in health care settings have evolved over time. When resistance to broad-spectrum antimicrobials mediated by extended-spectrum β-lactamases (ESBLs) arose in the 1980s, targeted interventions to slow spread were not widely promoted. However, when Enterobacteriaceae with carbapenemases that confer resistance to carbapenem antibiotics emerged, directed control efforts were recommended. These distinct approaches could have resulted in differences in spread of these two pathogens...
April 6, 2018: MMWR. Morbidity and Mortality Weekly Report
Amy Morgan, Mary O'Gara, Claudia Crilly Bellucci, Sebastian Linde, Meredith Albert, Arthur Curtis, Pravin Patel, Kathleen A Kapp-Simon
OBJECTIVE: The objective of this study was to investigate the impact of international adoption (IA), age at palatoplasty (PR age), and velopharyngeal sufficiency (VPS) on articulation outcomes. DESIGN: This was a cross-sectional, prospective, observational study. SETTING: Outpatient hospital clinic. PARTICIPANTS: Fifty-one IA and 65 not-adopted (NA) children between the ages of 3 and 9 with nonsyndromic cleft palate with or without cleft lip...
January 1, 2018: Cleft Palate-craniofacial Journal
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