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Tamara L Hendrickson
The introduction of manmade chemicals, including the herbicide atrazine, into the environment has led to the emergence of microorganisms with new biodegradation pathways. Esquirol et al. demonstrate that the AtzE enzyme catalyzes a central step in atrazine degradation and that expression of AtzE requires coexpression of the small protein AtzG. Remarkably, AtzG and AtzE appear to have evolved from GatC and GatA, components of an ancient enzyme involved in indirect tRNA aminoacylation, providing an elegant demonstration of metabolic repurposing...
May 18, 2018: Journal of Biological Chemistry
Wenlin Yuan, Jun Chen, Hongren Huang, Zhihui Cai, Qinjie Ling, Feng Huang, Zhi Huang
Arsenic (As) is a well-known environmental pollutant,while arsenic trioxide (ATO) has been proven to be an effective treatment for acute promyelocytic leukemia, however, the mechanism underlying its dual effects is not fully understood.Embryonic stem cells (ESCs) appear properties of stemness and serve as a popular model to investigate epigenetic modifiers includingenvironmental pollutants.Herein, the effect of low dose ATO on differentiation were evaluatedin vitro using a mouse ESCs (mESCs) cell line, CGR8...
May 16, 2018: Chemical Research in Toxicology
Maria Carmela Bonaccorsi di Patti, Antimo Cutone, Giovanni Musci
Fep1, the iron-dependent GATA-type transcriptional repressor of the methylotrophic yeast Pichia pastoris, has a dimeric structure and binds an iron-sulfur cluster of the [2Fe-2S] type. In this work, we extend the characterization of this protein by analysis of the optical and CD spectroscopic properties of a set of mutants where cysteines within the conserved Cys-X5 -Cys-X8- Cys-X2 -Cys motif have been targeted, in order to evaluate their role as [2Fe-2S] ligands. The results suggest that all four cysteine residues are essential because replacing them with serines in different combinations invariably produces a protein unable to correctly bind the [2Fe-2S] cluster...
May 14, 2018: Cell Biochemistry and Biophysics
Jing He, Xiaohong Zhang, Jiao Zhang, Ruizhong Zhang, Tianyou Yang, Jinhong Zhu, Huimin Xia, Yan Zou
Neuroblastoma is one of the most frequently occurring childhood cancers. The rs2168101 G>T polymorphism observed in the LMO1 gene is located at a conserved GATA transcription factor binding motif. This polymorphism was reported to be significantly associated with neuroblastoma susceptibility. However, whether this and other functional polymorphisms can affect neuroblastoma risk of Chinese children remains unknown. We conducted a two-center hospital-based case-control study with a total of 374 cases and 812 controls to assess the role of five LMO1 gene polymorphisms in the neuroblastoma risk...
2018: Journal of Cancer
Zongzhao Zhai, Jean-Philippe Boquete, Bruno Lemaitre
Intestinal infection triggers potent immune responses to combat pathogens and concomitantly drives epithelial renewal to maintain barrier integrity. Current models propose that epithelial renewal is primarily driven by damage caused by reactive oxygen species (ROS). Here we found that in Drosophila, the Imd-NF-κB pathway controlled enterocyte (EC) shedding upon infection, via a mechanism independent of ROS-associated apoptosis. Mechanistically, the Imd pathway synergized with JNK signaling to induce epithelial cell shedding specifically in the context of bacterial infection, requiring also the reduced expression of the transcription factor GATAe...
May 3, 2018: Immunity
Qin Zhu, Peifen Zheng, Jianying Zhou, Xinyu Chen, Yuliang Feng, Weifeng Wang, Feng Zhou, Qiaona He
Ulcerative colitis (UC) is a chronic, idiopathic, inflammatory bowel disease of the colon. T cell responses have been associated with the pathology of UC. Andrographis paniculata (AP) extract has been previously reported as an effective treatment of UC. The present study aimed to explore the effects of andrographolide, the primary active component of AP, on the T cell responses of patients with UC. Peripheral blood mononuclear cells (PBMCs) were isolated from patients with UC and treated with various concentrations of andrographolide (0, 10, 20 and 30 µg/ml)...
May 8, 2018: Molecular Medicine Reports
Mattias Möller, Yan Quan Lee, Karina Vidovic, Sven Kjellström, Linda Björkman, Jill R Storry, Martin L Olsson
The Xga blood group is differentially expressed on erythrocytes from males and females. The underlying gene, PBDX , was identified already in 1994 but the molecular background for Xga expression remains undefined. This gene, now designated XG , partly resides in the pseudoautosomal region 1 and encodes a protein of unknown function from the X chromosome. By comparing calculated Xga allele frequencies in different populations to 2,612 genetic variants in the XG region, rs311103 showed the strongest correlation to the expected distribution...
May 10, 2018: Blood
Haibo Su, Zhen Zhang, Zijian Liu, Baozhou Peng, Cong Kong, Honghai Wang, Zhi Zhang, Ying Xu
Targeting of Mycobacterium tuberculosis (MTB) PE/PPE antigens that induce type 1 helper T cell (Th1) and Th17 responses represents a crucial strategy for the development of tuberculosis (TB) vaccines. However, only few PE/PPE antigens induce these responses. Here, we sought to determine how the cell wall-associated antigen PPE60 (Rv3478) activates dendritic cell (DC) maturation and T-cell differentiation. We observed that PPE60 induces DC maturation by augmenting the protein expression of cluster of differentiation 80 (CD80) and CD86, and major histocompatibility complex (MHC) class I and MHC class II on the cell surface...
May 8, 2018: Journal of Biological Chemistry
Malgorzata Gozdecka, Eshwar Meduri, Milena Mazan, Konstantinos Tzelepis, Monika Dudek, Andrew J Knights, Mercedes Pardo, Lu Yu, Jyoti S Choudhary, Emmanouil Metzakopian, Vivek Iyer, Haiyang Yun, Naomi Park, Ignacio Varela, Ruben Bautista, Grace Collord, Oliver Dovey, Dimitrios A Garyfallos, Etienne De Braekeleer, Saki Kondo, Jonathan Cooper, Berthold Göttgens, Lars Bullinger, Paul A Northcott, David Adams, George S Vassiliou, Brian J P Huntly
The histone H3 Lys27-specific demethylase UTX (or KDM6A) is targeted by loss-of-function mutations in multiple cancers. Here, we demonstrate that UTX suppresses myeloid leukemogenesis through noncatalytic functions, a property shared with its catalytically inactive Y-chromosome paralog, UTY (or KDM6C). In keeping with this, we demonstrate concomitant loss/mutation of KDM6A (UTX) and UTY in multiple human cancers. Mechanistically, global genomic profiling showed only minor changes in H3K27me3 but significant and bidirectional alterations in H3K27ac and chromatin accessibility; a predominant loss of H3K4me1 modifications; alterations in ETS and GATA-factor binding; and altered gene expression after Utx loss...
May 7, 2018: Nature Genetics
Jing Tong, Xi-Jiang Hu, Wen-Qian Cai, Xiang Dai, Lei Wang
Puerarin has long been used as a traditional Chinese medicine, which possesses various physiological properties, including anti-inflammation, anti-oxidative, anti-diabetic and anti-cancer activities. The aim of the current study was to investigate the effect of puerarin on delayed-type hypersensitivity (DTH) induced by ovalbumin (OVA) in mice and explore its underlying mechanisms. The results showed that puerarin significantly attenuated DTH, resulting from a decrement in footpad swelling, reduction in inflammatory cell as well as a decline in anti-OVA IgG in serum...
May 2018: Experimental and Therapeutic Medicine
A Afek, L Tagliafierro, O C Glenn, D B Lukatsky, R Gordan, O Chiba-Falek
Short structural variants-variants other than single nucleotide polymorphisms-are hypothesized to contribute to many complex diseases, possibly by modulating gene expression. However, the molecular mechanisms by which noncoding short structural variants exert their effects on gene regulation have not been discovered. Here, we study simple sequence repeats (SSRs), a common class of short structural variants. Previously, we showed that repetitive sequences can directly influence the binding of transcription factors to their proximate recognition sites, a mechanism we termed non-consensus binding...
May 5, 2018: Neurogenetics
Radha Charan Dash, Angela M Zaino, M Kyle Hadden
The binding affinity between the histone 3 (H3) tail and the ADD domain of ATRX (ATRXADD ) increases with the subsequent addition of methyl groups on lysine 9 on H3. To improve our understanding of how the difference in methylation state affects binding between H3 and the ATRXADD , we adopted a metadynamic approach to explore the recognition mechanism between the two proteins and identify the key intermolecular interactions that mediate this protein-peptide interaction (PPI). The non-methylated H3 peptide is recognized only by the PHD finger of ATRXADD while mono-, di-, and trimethylated H3 is recognized by both the PHD and GATA-like zinc finger of the domain...
May 3, 2018: Biochimica et Biophysica Acta
Gurupreet S Sethi, Amarjit S Naura
Persistent inflammation and remodeling of airways are the major hallmarks of asthma. Though airway inflammation diminishes in ovalbumin (OVA)-based mouse model of chronic asthma owing to immune-tolerance linked with repeated allergen exposure, which limits the application of the disease model. Accordingly, the present study was designed to develop a murine model of chronic asthma which presents persistent airway inflammation coupled with remodeling traits. Herein, OVA-sensitized BALB/c mice were challenged with increasing (modified protocol) or constant concentration (conventional protocol) of the allergen for 6 weeks; 3 times/week...
May 2, 2018: International Immunopharmacology
Shiyao Wu, Yaou Zhou, Sijia Liu, Huali Zhang, Hui Luo, Xiaoxia Zuo, Tong Li
Previous research has demonstrated that nicotine have protective role in rheumatoid arthritis (RA). However, the immunologic mechanisms of nicotine's effect have not been fully elucidated. Herein, the effects of nicotine on the differentiation of Th1, Th2, and Th17 cells were assessed. Peripheral blood mononuclear cells (PBMCs) and CD4+T cells were separated from patients with RA. PBMCs were stimulated with anti-CD3/anti-CD28 in the absence or presence of nicotine. CD4+T cells were cultured in the Th cell differentiation condition in the absence of nicotine or nicotine and alpha- bungarotoxin (αBgt) (the antagonist of nicotine) combined...
April 28, 2018: European Journal of Pharmacology
Yanna Zhao, Xiaohua Sun, Xiaoling Yu, Ruilan Gao, Liming Yin
Aplastic anemia (AA) is usually treated with immunosuppressive agents, but their efficacy and safety are not satisfactory. Panax notoginseng saponins (PNS) promote the proliferation of hematopoietic stem/progenitor cells. This study aimed to examine the effects of leaf PNS (LPNS) on hematopoiesis and T cells in mouse models of AA. The experiments were performed in normal mice and AA mice (controls, cyclosporine, and low, medium, and high doses of LPNS). Hematopoietic cells were counted using colony formation assays...
April 2, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Daven N Jackson-Humbles, John Curtis Seely, Ronald A Herbert, David E Malarkey, Barry S McIntyre, Paul M Foster, Darlene Dixon
Congenital uterine wall cysts arising from paramesonephric (Müllerian) and mesonephric (Wolffian) ducts are typically incidental findings in most species. We used immunohistochemistry to characterize and determine the origin of uterine cysts in Sprague-Dawley (SD) rats from multigeneration studies conducted by the National Toxicology Program. Subserosal uterine cysts were observed in 20 of the 2,400 SD rats evaluated in five studies, and 10 cysts were characterized for this study. Single cysts were unilocular, fluid-filled, and occurred throughout the uterus...
January 1, 2018: Toxicologic Pathology
Cheng Tan, Xiaoyang Liu, Jiajun Chen
Purpose: This study aimed to investigate the underlying molecular mechanisms of Parkinson's disease (PD) by bioinformatics. Methods: Using the microarray dataset GSE72267 from the Gene Expression Omnibus database, which included 40 blood samples from PD patients and 19 matched controls, differentially expressed genes (DEGs) were identified after data preprocessing, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses...
2018: Parkinson's Disease
Miranda L Xu, Wilson K W Luk, Cathy W C Bi, Etta Y L Liu, Kevin Q Y Wu, Ping Yao, Tina T X Dong, Karl W K Tsim
Acetylcholinesterase (AChE; EC is known to hydrolyze acetylcholine at cholinergic synapses. In mammalian erythrocyte, AChE exists as a dimer (G2 ) and is proposed to play role in erythropoiesis. To reveal the regulation of AChE during differentiation of erythroblast, erythroblast-like cells (TF-1) were induced to differentiate by application of erythropoietin (EPO). The expression of AChE was increased in parallel to the stages of differentiation. Application of EPO in cultured TF-1 cells induced transcriptional activity of ACHE gene, as well as its protein product...
April 20, 2018: Journal of Neurochemistry
Adam J Dobson, Xiaoli He, Eric Blanc, Ekin Bolukbasi, Yodit Feseha, Mingyao Yang, Matthew D W Piper
Dietary restriction (DR) extends animal lifespan, but imposes fitness costs. This phenomenon depends on dietary essential amino acids (EAAs) and TOR signalling, which exert systemic effects. However, the roles of specific tissues and cell-autonomous transcriptional regulators in diverse aspects of the DR phenotype are unknown. Manipulating relevant transcription factors (TFs) specifically in lifespan-limiting tissues may separate the lifespan benefits of DR from the early-life fitness costs. Here, we systematically analyse transcription across organs of Drosophila subjected to DR or low TOR and predict regulatory TFs...
2018: NPJ Aging and Mechanisms of Disease
Jeoung-Eun Park, Sirshendu Majumdar, David D Brand, Edward F Rosloniec, Ae-Kyung Yi, John M Stuart, Andrew H Kang, Linda K Myers
The aim of this study was to understand how Syk affects peripheral T cell function. T cells from Syk-/- chimeric mice and DR1 Sykfl/fl CD4cre conditional mice gave strong CD3-induced Th1, Th2, and Th17 cytokine responses. However, an altered peptide ligand (APL) of human CII (256-276) with two substitutions (F263N, E266D), also called A12, elicited only Th2 cytokine responses from Sykfl/fl T cells but not Sykfl/fl- CD4cre T cells. Western blots revealed a marked increase in the phosphorylation of Syk, JNK and p38 upon A12/DR1 activation in WT or Sykfl/fl T cells but not in Sykfl/fl CD4-cre cells...
April 16, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
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