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Priya Tripathi, Furong Deng, Anne M Scruggs, Yahong Chen, Steven K Huang
Exposure to particulate matter < 2.5 μm (PM2.5 ) is associated with a variety of airway diseases. Although studies have demonstrated that high doses of PM2.5 cause cytotoxicity and changes to gene expression in bronchial epithelial cells, the effect of lower doses and repeated exposure to PM2.5 are less well studied. Here, we treated BEAS-2B cells with varying doses of PM2.5 for 1-7 days and examined the expression of a variety of genes implicated in airway disorders. At high doses, PM2.5 increased the expression of IL6, TNF, TSLP, CSF2, PTGS2, IL4R, and SPINK5...
May 9, 2018: Toxicology in Vitro: An International Journal Published in Association with BIBRA
Ronit Machtinger, Jia Zhong, Abdallah Mansur, Michal Adir, Catherine Racowsky, Russ Hauser, Kasey Brennan, Oskar Karlsson, Andrea A Baccarelli
Phthalates are endocrine disrupting chemicals (EDCs) that can cross the placenta and affect the fetal epigenome. Among various epigenetic regulators of gene expression, long non-coding RNAs (lncRNAs) are important players that may also be involved in the manifestation of EDC toxicity. We sought to explore the association between maternal urinary phthalate metabolite concentrations and lncRNA expression in human placenta to better understand potential mechanisms through which lncRNAs participate in mediating phthalate toxicity...
January 29, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
Youming Zhang, Thanushiyan Poobalasingam, Laura L Yates, Simone A Walker, Martin S Taylor, Lauren Chessum, Jackie Harrison, Loukia Tsaprouni, Ian M Adcock, Clare M Lloyd, William O Cookson, Miriam F Moffatt, Charlotte H Dean
We previously identified dipeptidylpeptidase 10 ( DPP10 ) on chromosome 2 as a human asthma susceptibility gene, through positional cloning. Initial association results were confirmed in many subsequent association studies but the functional role of DPP10 in asthma remains unclear. Using the MRC Harwell N-ethyl-N-nitrosourea (ENU) DNA archive, we identified a point mutation in Dpp10 that caused an amino acid change from valine to aspartic acid in the β-propeller region of the protein. Mice carrying this point mutation were recovered and a congenic line was established ( Dpp10145D )...
January 29, 2018: Disease Models & Mechanisms
Fang-Fen Yuan, Xue Gu, Xin Huang, Yu-Wei Hou, Yan Zhong, Jun Lin, Jing Wu
Attention-deficit/hyperactivity disorder (ADHD) is an early onset childhood neurodevelopmental disorder with high heritability. A number of genetic risk factors and environment factors have been implicated in the pathogenesis of ADHD. Genes encoding for subtypes of voltage-dependent K channels (Kv) and accessory proteins to these channels have been identified in genome-wide association studies (GWAS) of ADHD. We conducted a two-stage case-control study to investigate the associations between five key genes (KChIP4, KChIP1, DPP10, FHIT, and KCNC1) and the risk of developing ADHD...
2017: PloS One
Bangli Hu, Cheng Shi, Hai-Xing Jiang, Shan-Yu Qin
BACKGROUND: Gene alterations are crucial to the molecular pathogenesis of pancreatic cancer. The present study was designed to identify the potential candidate genes in the pancreatic carcinogenesis. METHODS: Gene Expression Omnibus database (GEO) datasets of pancreatic cancer tissue were retrieval and the differentially expressed genes (DEGs) from individual microarray data were merged. Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, protein-protein interaction (PPI) networks, and gene coexpression analysis were performed...
October 2017: Medicine (Baltimore)
Annisa Shui Lam Mak, Annie Ting Gee Chiu, Gordon Ka Chun Leung, Christopher Chun Yu Mak, Yoyo Wing Yiu Chu, Gary Tsz Kin Mok, Wing Fai Tang, Kelvin Yuen Kwong Chan, Mary Hoi Yin Tang, Elizabeth Tak-Kwong Lau Yim, Kin Wai So, Victoria Qinchen Tao, Cheuk Wing Fung, Virginia Chun Nei Wong, Mohammed Uddin, So Lun Lee, Christian R Marshall, Stephen W Scherer, Anita Sik Yau Kan, Brian Hon Yin Chung
BACKGROUND: Array comparative genomic hybridization (aCGH) is recommended as a first-tier genetic test for children with autism spectrum disorder (ASD). However, interpretation of results can often be challenging partly due to the fact that copy number variants (CNVs) in non-European ASD patients are not well studied. To address this literature gap, we report the CNV findings in a cohort of Chinese children with ASD. METHODS: DNA samples were obtained from 258 Chinese ASD patients recruited from a child assessment center between January 2011 and August 2014...
2017: Molecular Autism
Hartmut Heinrich, Juliane Grunitz, Valeska Stonawski, Stefan Frey, Simone Wahl, Björn Albrecht, Tamme W Goecke, Matthias W Beckmann, Johannes Kornhuber, Peter A Fasching, Gunther H Moll, Anna Eichler
In order to better understand the underpinnings of attention-deficit/hyperactivity disorder (ADHD), we targeted the relationship of attentional, cognitive control and motivational processes with DNA methylation patterns of 60 candidate genes in boys at early school age. Participants (6 to 8 years; N = 82) were selected from a German longitudinal cohort (FRANCES). ADHD-related behaviour was assessed via maternal ratings. Performance and event-related potential measures (inter alia Cue-P3 and Nogo-P3), which were recorded in a motivational go/nogo task, indicated diminished attentional orienting, reduced inhibitory response control and a larger motivational effect on performance in ADHD already at this relatively young age...
June 19, 2017: Scientific Reports
Yen-Ling Kuo, Jen-Kun Cheng, Wen-Hsien Hou, Yu-Cheng Chang, Po-Hao Du, Jhao-Jun Jian, Ruey-Horng Rau, Jung-Hui Yang, Cheng-Chang Lien, Meei-Ling Tsaur
The K(+) channel pore-forming subunit Kv4.3 is expressed in a subset of nonpeptidergic nociceptors within the dorsal root ganglion (DRG), and knockdown of Kv4.3 selectively induces mechanical hypersensitivity, a major symptom of neuropathic pain. K(+) channel modulatory subunits KChIP1, KChIP2, and DPP10 are coexpressed in Kv4.3(+) DRG neurons, but whether they participate in Kv4.3-mediated pain control is unknown. Here, we show the existence of a Kv4.3/KChIP1/KChIP2/DPP10 complex (abbreviated as the Kv4 complex) in the endoplasmic reticulum and cell surface of DRG neurons...
April 19, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Juan J Nieto-Fontarigo, Francisco J González-Barcala, Esther San José, Pilar Arias, Montserrat Nogueira, Francisco J Salgado
Asthma is a heterogeneous and chronic inflammatory family of disorders of the airways with increasing prevalence that results in recurrent and reversible bronchial obstruction and expiratory airflow limitation. These diseases arise from the interaction between environmental and genetic factors, which collaborate to cause increased susceptibility and severity. Many asthma susceptibility genes are linked to the immune system or encode enzymes like metalloproteases (e.g., ADAM-33) or serine proteases. The S9 family of serine proteases (prolyl oligopeptidases) is capable to process peptide bonds adjacent to proline, a kind of cleavage-resistant peptide bonds present in many growth factors, chemokines or cytokines that are important for asthma...
August 25, 2016: Clinical Reviews in Allergy & Immunology
Yohei Shiina, Tomohiro Muto, Zhili Zhang, Ahmad Baihaqie, Takamasa Yoshizawa, Hye-In J Lee, Eulsoon Park, Shinya Tsukiji, Koichi Takimoto
Mammalian DPP6 (DPPX) and DPP10 (DPPY) belong to a family of dipeptidyl peptidases, but lack enzyme activity. Instead, these proteins form complexes with voltage-gated K(+) channels in Kv4 family to control their gating and other properties. Here, we find that the fly DPP10 ortholog acts as an ancillary subunit of Kv4 channels and digests peptides. Similarly to mammalian DPP10, the fly ortholog tightly binds to rat Kv4.3 protein. The association causes negative shifts in voltage dependence of channel activation and steady state inactivation...
May 20, 2016: Scientific Reports
L Wagner, C Klemann, M Stephan, S von Hörsten
Dipeptidyl peptidase (DPP) 4 (CD26, DPP4) is a multi-functional protein involved in T cell activation by co-stimulation via its association with adenosine deaminase (ADA), caveolin-1, CARMA-1, CD45, mannose-6-phosphate/insulin growth factor-II receptor (M6P/IGFII-R) and C-X-C motif receptor 4 (CXC-R4). The proline-specific dipeptidyl peptidase also modulates the bioactivity of several chemokines. However, a number of enzymes displaying either DPP4-like activities or representing structural homologues have been discovered in the past two decades and are referred to as DPP4 activity and/or structure homologue (DASH) proteins...
June 2016: Clinical and Experimental Immunology
Chau-Fu Cheng, Wan-Chen Wang, Chia-Yi Huang, Po-Hau Du, Jung-Hui Yang, Meei-Ling Tsaur
Subthreshold A-type K(+) currents (ISA s) have been recorded from the somata of nociceptors and spinal lamina II excitatory interneurons, which sense and modulate pain, respectively. Kv4 channels are responsible for the somatodendritic ISA s. Accumulative evidence suggests that neuronal Kv4 channels are ternary complexes including pore-forming Kv4 subunits and two types of auxiliary subunits: K(+) channel-interacting proteins (KChIPs) and dipeptidyl peptidase-like proteins (DPPLs). Previous reports have shown Kv4...
March 1, 2016: Journal of Comparative Neurology
Masahiro Kitazawa, Yoshihiro Kubo, Koichi Nakajo
Kv4 is a member of the voltage-gated K(+) channel family and forms a complex with various accessory subunits. Dipeptidyl aminopeptidase-like protein (DPP) is one of the auxiliary subunits for the Kv4 channel. Although DPP has been well characterized and is known to increase the current amplitude and accelerate the inactivation and recovery from inactivation of Kv4 current, it remains to be determined how many DPPs bind to one Kv4 channel. To examine whether the expression level of DPP changes the biophysical properties of Kv4, we expressed Kv4...
September 11, 2015: Journal of Biological Chemistry
Hanga Galfalvy, Fatemeh Haghighi, Colin Hodgkinson, David Goldman, Maria A Oquendo, Ainsley Burke, Yung-Yu Huang, Ina Giegling, Dan Rujescu, Alexandre Bureau, Gustavo Turecki, J John Mann
Genome wide array studies have reported limited success in identifying genetic markers conferring risk for suicidal behavior (SB). This may be attributable to study designs with primary outcome other than SB. We performed a GWAS on suicides and cases with a history of nonfatal suicide attempts compared with psychiatric controls and healthy volunteers. A consortium of USA, Canadian and German teams assembled two groups of cases (suicide attempters and suicides, N = 577) and non-attempter psychiatric and healthy controls (N = 1,233)...
October 2015: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
Michelle Cotterchio, Elizabeth Lowcock, Zoe Bider-Canfield, Mathieu Lemire, Celia Greenwood, Steven Gallinger, Thomas Hudson
BACKGROUND: Many epidemiology studies report that atopic conditions such as allergies are associated with reduced pancreas cancer risk. The reason for this relationship is not yet understood. This is the first study to comprehensively evaluate the association between variants in atopy-related candidate genes and pancreatic cancer risk. METHODS: A population-based case-control study of pancreas cancer cases diagnosed during 2011-2012 (via Ontario Cancer Registry), and controls recruited using random digit dialing utilized DNA from 179 cases and 566 controls...
2015: PloS One
Gustavo Arruda Bezerra, Elena Dobrovetsky, Alma Seitova, Sofiya Fedosyuk, Sirano Dhe-Paganon, Karl Gruber
The voltage-gated potassium channel family (Kv) constitutes the most diverse class of ion channels in the nervous system. Dipeptidyl peptidase 10 (DPP10) is an inactive peptidase that modulates the electrophysiological properties, cell-surface expression and subcellular localization of voltage-gated potassium channels. As a consequence, DPP10 malfunctioning is associated with neurodegenerative conditions like Alzheimer and fronto-temporal dementia, making this protein an attractive drug target. In this work, we report the crystal structure of DPP10 and compare it to that of DPP6 and DPP4...
2015: Scientific Reports
K Turnow, K Metzner, D Cotella, M J Morales, M Schaefer, T Christ, U Ravens, E Wettwer, S Kämmerer
The sustained component of the K(+) outward current in human atrial myocytes is believed to be due to the slowly inactivating ultra-rapid potassium current I Kur and not to the fast inactivating transient outward current Ito. Here we provide evidence for contribution of Ito to this late current due to the effects of dipeptidyl peptidase-like protein (DPP) 10 (DPP10a) interacting with Kv4.3 channels. We studied the late current component of Ito in human atrial myocytes and CHO cells co-expressing Kv4.3 or Kv4...
March 2015: Basic Research in Cardiology
Seung-Hyun Kim, Hyunna Choi, Moon-Gyung Yoon, Young-Min Ye, Hae-Sim Park
BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is an endotype of severe and eosinophilic adult asthma characterized by chronic rhinosinusitis with nasal polyps and hypersensitivity to aspirin and/or nonsteroidal anti-inflammatory drugs. A genetic contribution of dipeptidyl-peptidase 10 (DPP10) to asthma susceptibility and lung function decline has been reported. However, little is known about the role of DPP10 in the pathogenesis of AERD. OBJECTIVE: To identify genetic variants of DPP10 that confer susceptibility to AERD or severe asthma...
March 2015: Annals of Allergy, Asthma & Immunology
Divya Chhabra, Sunita Sharma, Alvin T Kho, Roger Gaedigk, Carrie A Vyhlidal, J Steven Leeder, Jarrett Morrow, Vincent J Carey, Scott T Weiss, Kelan G Tantisira, Dawn L DeMeo
In utero smoke exposure has been shown to have detrimental effects on lung function and to be associated with persistent wheezing and asthma in children. One potential mechanism of IUS effects could be alterations in DNA methylation, which may have life-long implications. The goal of this study was to examine the association between DNA methylation and nicotine exposure in fetal lung and placental tissue in early development; nicotine exposure in this analysis represents a likely surrogate for in-utero smoke...
November 2014: Epigenetics: Official Journal of the DNA Methylation Society
Wan-Chen Wang, Chau-Fu Cheng, Meei-Ling Tsaur
Subthreshold A-type K(+) currents (ISA s) have been recorded from the cell bodies of hippocampal and neocortical interneurons as well as neocortical pyramidal neurons. Kv4 channels are responsible for the somatodendritic ISA s. It has been proposed that neuronal Kv4 channels are ternary complexes including pore-forming Kv4 subunits, K(+) channel-interacting proteins (KChIPs), and dipeptidyl peptidase-like proteins (DPPLs). However, colocalization evidence was still lacking. The distribution of DPP10 mRNA in rodent brain has been reported but its protein localization remains unknown...
March 1, 2015: Journal of Comparative Neurology
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