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Lei Liu, Naoki Watanabe, Hiroyasu Akatsu, Masaki Nishimura
Decrease in brain amyloid-β (Aβ) accumulation is a leading strategy for treating Alzheimer's disease (AD). However, the intrinsic mechanism of the regulation of brain Aβ production is largely unknown. Previously, we reported that ILEI (also referred to as FAM3C) binds to the γ-secretase complex and suppresses Aβ production without inhibiting γ-secretase activity. In this study, we examined ILEI expression in mouse brain using immunohistochemistry and subcellular fractionation. Brain ILEI showed widespread expression in neurons and ependymal cells but not in glial and vascular endothelial cells...
August 25, 2016: Neuroscience
Jorma A Määttä, Ameya Bendre, Mervi Laanti, Kalman G Büki, Pia Rantakari, Päivi Tervola, Johanna Saarimäki, Matti Poutanen, Pirkko Härkönen, Kalervo Väänänen
Fam3c, a cytokine-like growth factor, has been suggested to have a role in epithelial-to-mesenchymal transition (EMT), tumor growth and metastasis. A single-nucleotide polymorphism affecting bone mineral density has been found in the first intron of the Fam3c gene in a study analyzing an Asian population cohort. Other independent studies on different population cohorts have found the fam3c locus to be associated with bone mineral density and fractures. In order to investigate the role of Fam3c in bone biology, we have generated a Fam3c knock-out (KO) mouse strain...
2016: BoneKEy Reports
Nils Halberg, Caitlin A Sengelaub, Kristina Navrazhina, Henrik Molina, Kunihiro Uryu, Sohail F Tavazoie
Enhanced secretion of tumorigenic effector proteins is a feature of malignant cells. The molecular mechanisms underlying this feature are poorly defined. We identify PITPNC1 as a gene amplified in a large fraction of human breast cancer and overexpressed in metastatic breast, melanoma, and colon cancers. Biochemical, molecular, and cell-biological studies reveal that PITPNC1 promotes malignant secretion by binding Golgi-resident PI4P and localizing RAB1B to the Golgi. RAB1B localization to the Golgi allows for the recruitment of GOLPH3, which facilitates Golgi extension and enhanced vesicular release...
March 14, 2016: Cancer Cell
Xinjian Peng, Enquan Xu, Weiwei Liang, Xiaolei Pei, Dixin Chen, Danfeng Zheng, Yang Zhang, Can Zheng, Pingzhang Wang, Shaoping She, Yan Zhang, Jing Ma, Xiaoning Mo, Yingmei Zhang, Dalong Ma, Ying Wang
The family with sequence similarity 3 (FAM3) gene family is a cytokine-like gene family with four members FAM3A, FAM3B, FAM3C and FAM3D. In this study, we found that FAM3D strongly chemoattracted human peripheral blood neutrophils and monocytes. To identify the FAM3D receptor, we used chemotaxis, receptor internalization, Ca(2+) flux and radioligand-binding assays in FAM3D-stimulated HEK293 cells that transiently expressed formyl peptide receptor (FPR)1 or FPR2 to show that FAM3D was a high affinity ligand of these receptors, both of which were highly expressed on the surface of neutrophils, and monocytes and macrophages...
May 1, 2016: Journal of Cell Science
Alessandra Chesi, Jonathan A Mitchell, Heidi J Kalkwarf, Jonathan P Bradfield, Joan M Lappe, Shana E McCormack, Vicente Gilsanz, Sharon E Oberfield, Hakon Hakonarson, John A Shepherd, Andrea Kelly, Babette S Zemel, Struan F A Grant
Childhood fractures are common, with the forearm being the most common site. Genome-wide association studies (GWAS) have identified more than 60 loci associated with bone mineral density (BMD) in adults but less is known about genetic influences specific to bone in childhood. To identify novel genetic factors that influence pediatric bone strength at a common site for childhood fractures, we performed a sex-stratified trans-ethnic genome-wide association study of areal BMD (aBMD) and bone mineral content (BMC) Z-scores measured by dual energy X-ray absorptiometry at the one-third distal radius, in a cohort of 1399 children without clinical abnormalities in bone health...
September 1, 2015: Human Molecular Genetics
Adam A Kraya, Shengfu Piao, Xiaowei Xu, Gao Zhang, Meenhard Herlyn, Phyllis Gimotty, Beth Levine, Ravi K Amaravadi, David W Speicher
Macroautophagy, a catabolic process of cellular self-digestion, is an important tumor cell survival mechanism and a potential target in antineoplastic therapies. Recent discoveries have implicated autophagy in the cellular secretory process, but potential roles of autophagy-mediated secretion in modifying the tumor microenvironment are poorly understood. Furthermore, efforts to inhibit autophagy in clinical trials have been hampered by suboptimal methods to quantitatively measure tumor autophagy levels. Here, we leveraged the autophagy-based involvement in cellular secretion to identify shed proteins associated with autophagy levels in melanoma...
2015: Autophagy
Lei Zhang, Hyung Jin Choi, Karol Estrada, Paul J Leo, Jian Li, Yu-Fang Pei, Yinping Zhang, Yong Lin, Hui Shen, Yao-Zhong Liu, Yongjun Liu, Yingchun Zhao, Ji-Gang Zhang, Qing Tian, Yu-ping Wang, Yingying Han, Shu Ran, Rong Hai, Xue-Zhen Zhu, Shuyan Wu, Han Yan, Xiaogang Liu, Tie-Lin Yang, Yan Guo, Feng Zhang, Yan-fang Guo, Yuan Chen, Xiangding Chen, Lijun Tan, Lishu Zhang, Fei-Yan Deng, Hongyi Deng, Fernando Rivadeneira, Emma L Duncan, Jong Young Lee, Bok Ghee Han, Nam H Cho, Geoffrey C Nicholson, Eugene McCloskey, Richard Eastell, Richard L Prince, John A Eisman, Graeme Jones, Ian R Reid, Philip N Sambrook, Elaine M Dennison, Patrick Danoy, Laura M Yerges-Armstrong, Elizabeth A Streeten, Tian Hu, Shuanglin Xiang, Christopher J Papasian, Matthew A Brown, Chan Soo Shin, André G Uitterlinden, Hong-Wen Deng
Aiming to identify novel genetic variants and to confirm previously identified genetic variants associated with bone mineral density (BMD), we conducted a three-stage genome-wide association (GWA) meta-analysis in 27 061 study subjects. Stage 1 meta-analyzed seven GWA samples and 11 140 subjects for BMDs at the lumbar spine, hip and femoral neck, followed by a Stage 2 in silico replication of 33 SNPs in 9258 subjects, and by a Stage 3 de novo validation of three SNPs in 6663 subjects. Combining evidence from all the stages, we have identified two novel loci that have not been reported previously at the genome-wide significance (GWS; 5...
April 1, 2014: Human Molecular Genetics
Seok Jin Kim, Insuk Sohn, In-Gu Do, Sin Ho Jung, Young Hyeh Ko, Hae Yong Yoo, Soonmyung Paik, Won Seog Kim
We performed the whole genome cDNA-mediated annealing, selection and ligation assay with 164 formalin-fixed paraffin-embedded (FFPE) tumor samples to develop robust prognostic gene expression profiles in patients with diffuse large B cell lymphoma. The prognostic gene expression profiles were developed and validated by a gradient lasso and leave-one-out cross-validation process. We identified a set of genes whose expression provided prognostic indicators from whole data set (PRKCDBP, CASP10, FAM3C, KCNK12, MAN1A2, PRND, RAB1A, TMEM39B, SLC6A6, MMP12, FEM1B, C3orh37, RBP1, HK1, LOC400464, KIAA0746, and SLC25A23)...
March 2014: Annals of Hematology
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No abstract text is available yet for this article.
2012: BoneKEy Reports
Jichun Yang, Youfei Guan
Nonalcoholic fatty liver disease (NAFLD) comprises a disease spectrum ranging from simple steatosis (fatty liver) and nonalcoholic steatohepatitis to fibrosis and cirrhosis. NAFLD has become the leading cause of chronic liver diseases as well as liver-related morbidity and mortality worldwide. NAFLD is also associated with increased risk of cardiovascular diseases, hyperlipidemia, and type 2 diabetes. Insulin resistance in adipose tissues and the liver plays crucial roles in the progression of NAFLD. The family with sequence similarity 3 (FAM3) gene family is a cytokine-like gene family with four members designated FAM3A, FAM3B, FAM3C, and FAM3D, respectively...
August 2013: Journal of Gastroenterology and Hepatology
Patrik Johansson, Jenny Bernström, Tracy Gorman, Linda Oster, Stefan Bäckström, Fritz Schweikart, Bingze Xu, Yafeng Xue, Lovisa Holmberg Schiavone
The FAM3 superfamily is predicted to contain classical four-helix bundle cytokines, featuring a typical up-up-down-down fold. Two members of FAM3 have been extensively studied. FAM3B PANDER has been shown to regulate glucose homeostasis and β cell function, whereas the homologous FAM3C ILEI has been shown to be involved in epithelial-mesenchymal transition and cancer. Here, we present a three-dimensional structure of a FAM3 protein, murine PANDER. Contrary to previous suggestions, PANDER exhibits a globular β-β-α fold...
February 5, 2013: Structure
Jun Zhu, Jun Qiu, Gregg Magrane, Malak Abedalthagafi, Andrea Zanko, Mahin Golabi, Farid F Chehab
We characterized the t(7;22)(q32;q11.2) chromosomal translocation in an obese female with coarse features, short stature, developmental delay and a hypoplastic fifth digit. While these clinical features suggest Coffin-Siris Syndrome (CSS), we excluded a CSS diagnosis by exome sequencing based on the absence of deleterious mutations in six chromatin-remodeling genes recently shown to cause CSS. Thus, molecular characterization of her translocation could delineate genes that underlie other syndromes resembling CSS...
2012: PloS One
Yi-Hsiang Hsu, Douglas P Kiel
CONTEXT: The primary goals of genome-wide association studies (GWAS) are to discover new molecular and biological pathways involved in the regulation of bone metabolism that can be leveraged for drug development. In addition, the identified genetic determinants may be used to enhance current risk factor profiles. EVIDENCE ACQUISITION: There have been more than 40 published GWAS on skeletal phenotypes, predominantly focused on dual-energy x-ray absorptiometry-derived bone mineral density (BMD) of the hip and spine...
October 2012: Journal of Clinical Endocrinology and Metabolism
Hou-Feng Zheng, Jon H Tobias, Emma Duncan, David M Evans, Joel Eriksson, Lavinia Paternoster, Laura M Yerges-Armstrong, Terho Lehtimäki, Ulrica Bergström, Mika Kähönen, Paul J Leo, Olli Raitakari, Marika Laaksonen, Geoffrey C Nicholson, Jorma Viikari, Martin Ladouceur, Leo-Pekka Lyytikäinen, Carolina Medina-Gomez, Fernando Rivadeneira, Richard L Prince, Harri Sievanen, William D Leslie, Dan Mellström, John A Eisman, Sofia Movérare-Skrtic, David Goltzman, David A Hanley, Graeme Jones, Beate St Pourcain, Yongjun Xiao, Nicholas J Timpson, George Davey Smith, Ian R Reid, Susan M Ring, Philip N Sambrook, Magnus Karlsson, Elaine M Dennison, John P Kemp, Patrick Danoy, Adrian Sayers, Scott G Wilson, Maria Nethander, Eugene McCloskey, Liesbeth Vandenput, Richard Eastell, Jeff Liu, Tim Spector, Braxton D Mitchell, Elizabeth A Streeten, Robert Brommage, Ulrika Pettersson-Kymmer, Matthew A Brown, Claes Ohlsson, J Brent Richards, Mattias Lorentzon
We aimed to identify genetic variants associated with cortical bone thickness (CBT) and bone mineral density (BMD) by performing two separate genome-wide association study (GWAS) meta-analyses for CBT in 3 cohorts comprising 5,878 European subjects and for BMD in 5 cohorts comprising 5,672 individuals. We then assessed selected single-nucleotide polymorphisms (SNPs) for osteoporotic fracture in 2,023 cases and 3,740 controls. Association with CBT and forearm BMD was tested for ∼2.5 million SNPs in each cohort separately, and results were meta-analyzed using fixed effect meta-analysis...
July 2012: PLoS Genetics
L-S Zhang, H-G Hu, Y-J Liu, J Li, P Yu, F Zhang, T-L Yang, Q Tian, Y-P Zheng, Y Guo, H-W Deng
SUMMARY: We tested whether two genetic variants were associated with BMD at multiple clinically relevant skeletal sites in Caucasians. We found that variant rs7776725 is consistently associated with hip, spine, wrist and whole-body BMD, which highlights the potential importance of this variant or linked variants for osteoporosis. INTRODUCTION: A recent genome-wide association study identified two single nucleotide polymorphisms (SNPs), rs7776725 and rs1721400, that were associated with bone mineral density (BMD) variation at the radius, tibia and calcaneus in a Korean population...
July 2012: Osteoporosis International
Matthew R Richardson, Zaneer M Segu, Marianne O Price, Xianyin Lai, Frank A Witzmann, Yehia Mechref, Mervin C Yoder, Francis W Price
Fuchs endothelial corneal dystrophy (FECD) is a progressive disorder characterized by corneal endothelial decompensation leading to corneal edema, clouding, and vision impairment. Despite improved understanding over the last century since its first description, the exact mechanism(s) behind the pathogenesis of FECD remain unknown, and surgical correction is the only effective treatment available. Previous studies have suggested a role for changes in aqueous humor (AH) composition in FECD pathogenesis, so to explore this possibility, we probed the AH proteome for alterations correlating with end-stage corneal disease...
2010: Molecular Vision
Tatsuya Katahira, Shiho Nakagiri, Koji Terada, Takahisa Furukawa
FAM3C is a secreted factor, which is involved in the epithelial to mesenchymal transition. In transcriptome profiling of the mouse retina using microarray, we found that FAM3C is highly expressed in the retina. FAM3C is expressed in the ganglion cell layer (GCL) of the retina. To explore the function of FAM3C in retinal development, we cloned Xenopus FAM3C (XFAM3C), and performed Xenopus gain- and loss-of-function analysis. Overexpression of XFAM3C resulted in retinal laminar disorganization and an increase in eye size...
February 12, 2010: Biochemical and Biophysical Research Communications
Bai-Yu Lee, Deepa Jethwaney, Birgit Schilling, Daniel L Clemens, Bradford W Gibson, Marcus A Horwitz
Mycobacterium tuberculosis and Mycobacterium bovis bacille Calmette-Guérin (BCG) alter the maturation of their phagosomes and reside within a compartment that resists acidification and fusion with lysosomes. To define the molecular composition of this compartment, we developed a novel method for obtaining highly purified phagosomes from BCG-infected human macrophages and analyzed the phagosomes by Western immunoblotting and mass spectrometry-based proteomics. Our purification procedure revealed that BCG grown on artificial medium becomes less dense after growth in macrophages...
January 2010: Molecular & Cellular Proteomics: MCP
Yoon Shin Cho, Min Jin Go, Young Jin Kim, Jee Yeon Heo, Ji Hee Oh, Hyo-Jeong Ban, Dankyu Yoon, Mi Hee Lee, Dong-Joon Kim, Miey Park, Seung-Hun Cha, Jun-Woo Kim, Bok-Ghee Han, Haesook Min, Younjhin Ahn, Man Suk Park, Hye Ree Han, Hye-Yoon Jang, Eun Young Cho, Jong-Eun Lee, Nam H Cho, Chol Shin, Taesung Park, Ji Wan Park, Jong-Keuk Lee, Lon Cardon, Geraldine Clarke, Mark I McCarthy, Jong-Young Lee, Jong-Koo Lee, Bermseok Oh, Hyung-Lae Kim
To identify genetic factors influencing quantitative traits of biomedical importance, we conducted a genome-wide association study in 8,842 samples from population-based cohorts recruited in Korea. For height and body mass index, most variants detected overlapped those reported in European samples. For the other traits examined, replication of promising GWAS signals in 7,861 independent Korean samples identified six previously unknown loci. For pulse rate, signals reaching genome-wide significance mapped to chromosomes 1q32 (rs12731740, P = 2...
May 2009: Nature Genetics
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