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Leonardo Elia, Paolo Kunderfranco, Pierluigi Carullo, Marco Vacchiano, Floriana Maria Farina, Ignacio Fernando Hall, Stefano Mantero, Cristina Panico, Roberto Papait, Gianluigi Condorelli, Manuela Quintavalle
Adult vascular smooth muscle cells (VSMCs) possess the peculiar ability to de-differentiate in response to extracellular cues, such as vascular damage and inflammation. De-differentiated VSMCs are proliferative, migratory, and have decreased contractile capacity. VSMC dedifferentiation contributes not only to vascular repair, but also to cardiovascular pathologies, such as intimal hyperplasia/restenosis in coronary artery or peripheral vascular diseases and arterial aneurysm. We here demonstrate the role of ubiquitin-like, containing PHD and RING finger domains, 1 (UHRF1) as an epigenetic master regulator of VSMC plasticity...
March 20, 2018: Journal of Clinical Investigation
Huan Liu, Gang Wang, Wei Li, Xingzhong Liu, Erwei Li, Wen-Bing Yin
Trichoderma hypoxylon is a fungicolous species which produces rich secondary metabolites. However, no genetic transformation method is available for further studies. Here, we developed a marker-less transformation system based on the complementation of an uridine/uracil biosynthetic gene by protoplast transformation. An uridine/uracil auxotrophic mutant of Δthpyr4 was obtained by using a positive screening protocol with 5'-fluoroorotic acid as a selective reagent. To improve the homologous integration rates, the orthologues of ku70 and lig4 which play critical roles in non-homologous end-joining recombination were disrupted...
March 19, 2018: Microbiology
A M Vaira, H S Lim, G Bauchan, C J Gulbronson, L Miozzi, N Vinals, A Natilla, J Hammond
The Lolium latent virus (LoLV) major coat protein sequence contains a typical chloroplast transit peptide (cTP) domain. In infected Nicotiana benthamiana leaf tissue, LoLV coat proteins can be detected at the chloroplast. In transient expression, several N-terminal deletions of the CP sequence, increasing in length, result in disruption of the domain functionality, markedly affecting intracellular localization. A yeast two-hybrid-based study using LoLV CP as bait identified several potentially interacting Arabidopsis host proteins, most of them with chloroplast-linked pathways...
March 20, 2018: Journal of General Virology
Nigani Willie, Rajeev K Mehlotra, Rosalind E Howes, Tovonahary A Rakotomanga, Stephanie Ramboarina, Arsène C Ratsimbasoa, Peter A Zimmerman
Plasmodium falciparum histidine-rich protein 2 (PfHRP2) forms the basis of many current malaria rapid diagnostic tests (RDTs). However, the parasites lacking part or all of the pfhrp2 gene do not express the PfHRP2 protein and are, therefore, not identifiable by PfHRP2-detecting RDTs. We evaluated the performance of the SD Bioline Malaria Ag P.f/Pan RDT together with pfhrp2 variation in Madagascar. Genomic DNA isolated from 260 patient blood samples were polymerase chain reaction (PCR)-amplified for the parasite 18S rRNA and pfhrp2 genes...
March 19, 2018: American Journal of Tropical Medicine and Hygiene
Bo Geum Choi, Su Kyung Hwang, Jung Eun Kwon, Yeo Hyang Kim
BACKGROUND AND OBJECTIVES: The purpose of the present study was to investigate the advantages and disadvantages of verifying genetic abnormalities using array comparative genomic hybridization (a-CGH) immediately after diagnosis of congenital heart disease (CHD). METHODS: Among neonates under the age of 28 days who underwent echocardiography from January 1, 2014 to April 30, 2016, neonates whose chromosomal and genomic abnormalities were tested using a-CGH in cases of an abnormal finding on echocardiography were enrolled...
March 2018: Korean Circulation Journal
Yingyi Liu, Shuo Zhang, Qi Xu, Jiajun Wu, Xinyan Zhai, Shuo Li, Jing Wang, Jianqiang Ni, Lin Yuan, Xiaohui Song, Bolin Zhao, Zhi Zhou, Chuanbin Wang, Lin Yang
Pseudorabies (PR) has been prevalent in Chinese swine breeding farms since the outbreak at the end of 2011. For investigating current prevalence of PR, a nationwide surveillance has been performed in this study. The swine serum samples were collected from 93, 100, 92, and 91 swine farms in China during 2013-2016, respectively. Since the extensive use of gE-deleted pseudorabies virus (PRV) vaccine, we could apply the PRV-gE antibody for determining wild-type virus infection and the PRV-gB antibody for evaluating vaccine immunization...
March 19, 2018: Tropical Animal Health and Production
Xiangchun Li, Weiqi Xu, Wei Kang, Sunny H Wong, Mengyao Wang, Yong Zhou, Xiaodong Fang, Xiuqing Zhang, Huanming Yang, Chi H Wong, Ka F To, Stephen L Chan, Matthew T V Chan, Joseph J Y Sung, William K K Wu, Jun Yu
Objective: Hepatocellular carcinoma (HCC) is a highly heterogeneous disease with a dismal prognosis. However, driver genes and prognostic markers in HCC remain to be identified. It is hoped that in-depth analysis of HCC genomes in relation to available clinicopathological information will give rise to novel molecular prognostic markers. Methods: We collected genomic data of 1,061 HCC patients from previous studies, and performed integrative analysis to identify significantly mutated genes and molecular prognosticators...
2018: Theranostics
Chun-Yuan Chen, Shan-Shan Rao, Lu Ren, Xiong-Ke Hu, Yi-Juan Tan, Yin Hu, Juan Luo, Yi-Wei Liu, Hao Yin, Jie Huang, Jia Cao, Zhen-Xing Wang, Zheng-Zhao Liu, Hao-Ming Liu, Si-Yuan Tang, Ran Xu, Hui Xie
Chronic non-healing wounds represent one of the most common complications of diabetes and need advanced treatment strategies. Exosomes are key mediators of cell paracrine action and can be directly utilized as therapeutic agents for tissue repair and regeneration. Here, we explored the effects of exosomes from human urine-derived stem cells (USC-Exos) on diabetic wound healing and the underlying mechanism. Methods: USCs were characterized by flow cytometry and multipotent differentiation potential analyses...
2018: Theranostics
Chuang Qu, Shuhui Gao, Hongwei Shao, Wenfeng Zhang, Huabben Bo, Xin Lu, Tianjiao Chen, Jing Kou, Yue Wang, Gui Si Chen, Shulin Huang, Han Shen
Cluster of differentiation (CD)147 is highly expressed in drug-resistant tumor cell lines and is involved in the formation of tumor drug resistance. Therefore, immunotherapy utilizing CD147 epitope peptides is a promising approach for the elimination of drug-resistant tumor cells. However, like most tumor-associated antigens (TAAs), CD147 belongs to the autoantigen category, and T cells that recognize high affinity, immunodominant epitopes from autoantigens are deleted though thymic negative selection. Furthermore, wild-type autoantigen peptides cannot effectively activate and expand T lymphocytes with lower affinity T cell receptors in vivo ...
April 2018: Oncology Letters
Jing Yuan, Xinshuang Yu, Aihua Wang, Yan Li, Fengjun Liu, Yao Wang, Shanmei Sun, Xiuyang Bing, Yiming Liu, Juan Du
For several years, the cause of autosomal recessive mental retardation has been attributed to the deletion or mutation of a gene named tumor suppressor candidate 3 (TUSC3). Previous research has identified that TUSC3 is a potential tumor suppressor gene in oral epidermoid carcinoma, lung cancer and esophageal cancer. However, to the best of our knowledge, no previously published data has existed on the expression of TUSC3 in gliomas. The present study focused on the expression of TUSC3 in brain gliomas. Additionally, the present study sought to identify he association between TUSC3 expression and the typical clinical and pathological disease manifestations of gliomas...
April 2018: Oncology Letters
Gabrielle Bradshaw, Robbie R Lualhati, Cassie L Albury, Neven Maksemous, Deidre Roos-Araujo, Robert A Smith, Miles C Benton, David A Eccles, Rod A Lea, Heidi G Sutherland, Larisa M Haupt, Lyn R Griffiths
Background: We investigated the molecular etiology of a young male proband with confirmed immunodeficiency of unknown cause, presenting with recurrent bacterial and Varicella zoster viral infections in childhood and persistent lymphopenia into early adulthood. Aim: To identify causative functional genetic variants related to an undiagnosed primary immunodeficiency. Method: Whole genome microarray copy number variant (CNV) analysis was performed on the proband followed by whole exome sequencing (WES) and trio analysis of the proband and family members...
2018: Frontiers in Immunology
Joaquín Letelier, Elisa de la Calle-Mustienes, Joyce Pieretti, Silvia Naranjo, Ignacio Maeso, Tetsuya Nakamura, Juan Pascual-Anaya, Neil H Shubin, Igor Schneider, Juan Ramón Martinez-Morales, José Luis Gómez-Skarmeta
Despite their evolutionary, developmental and functional importance, the origin of vertebrate paired appendages remains uncertain. In mice, a single enhancer termed ZRS is solely responsible for Shh expression in limbs. Here, zebrafish and mouse transgenic assays trace the functional equivalence of ZRS across the gnathostome phylogeny. CRISPR/Cas9-mediated deletion of the medaka (Oryzias latipes) ZRS and enhancer assays identify the existence of ZRS shadow enhancers in both teleost and human genomes. Deletion of both ZRS and shadow ZRS abolishes shh expression and completely truncates pectoral fin formation...
March 19, 2018: Nature Genetics
Monica Traverso, Stefania Assereto, Serena Baratto, Michele Iacomino, Marina Pedemonte, Maria Cristina Diana, Marta Ferretti, Paolo Broda, Carlo Minetti, Elisabetta Gazzerro, Francesca Madia, Claudio Bruno, Federico Zara, Chiara Fiorillo
We present a 13-year-old patient with persistent increase of serum Creatine Kinase (CK) and myalgia after exertion. Skeletal muscle biopsy showed marked reduction of dystrophin expression leading to genetic analysis of DMD gene by MLPA, which detected a single deletion of exon 78. To the best of our knowledge, DMD exon 78 deletion has never been described in literature and, according to prediction, it should lead to loss of reading frame in the dystrophin gene. To further assess the actual effect of exon 78 deletion, we analysed cDNA from muscle mRNA...
March 19, 2018: Journal of Human Genetics
Tom Verbiest, Rosemary Finnon, Natalie Brown, Lourdes Cruz-Garcia, Paul Finnon, Grainne O'Brien, Eleanor Ross, Simon Bouffler, Cheryl L Scudamore, Christophe Badie
Epidemiological studies have demonstrated an increased leukemia incidence following ionizing radiation exposure, but to date, the target cells and underlying mechanisms of radiation leukemogenesis remain largely unidentified. We engineered a mouse model carrying a different fluorescent marker on each chromosome 2, located inside the minimum deleted region occurring after radiation exposure and recognized as the first leukemogenic event. Using this tailored model, we report that following radiation exposure, more than half of asymptomatic CBA Sfpi1 GFP/mCh mice presented with expanding clones of preleukemic hematopoietic cells harboring a hemizygous interstitial deletion of chromosome 2...
March 3, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Mone Zaidi, Maria New, Harry C Blair, Alberta Zallone, Ramkumarie Baliram, Terry F Davies, Christopher Cardozo, James Iqbal, Li Sun, Cliff Rosen, Tony Yuen
It has become increasingly clear that pituitary hormones that have traditionally been seen as regulators of single bodily processes, including endocrine functions, have additional roles in physiology. The global deletion of these hormones or their receptors in mice has yielded unexpected skeletal and metabolic phenotypes, which have been confirmed through traditional pharmacologic approaches. Initial reports showed that thyroid-stimulating hormone receptors were expressed on bone cells and that their haploinsufficiency in Tshr+/- mice caused osteopenia without affecting the thyroid function...
March 19, 2018: Journal of Endocrinology
Kai Li, Yue Zhang, Yuwei Zhang, Wenqing Jiang, Junhui Shen, Song Xu, Daozhang Cai, Jie Shen, Bin Huang, Mangmang Li, Qiancheng Song, Yu Jiang, Anling Liu, Xiaochun Bai
OBJECTIVES: To investigate the role of tyrosine kinase Fyn in the development of osteoarthritis (OA) and the underlying mechanisms, and to define whether targeting Fyn could prevent OA in mice. METHODS: Cartilage samples from normal and aged mice were analysed with proteome-wide screening. Fyn expression was examined with immunofluorescence in human and age-dependent or experimental mouse OA cartilage samples. Experimental OA in Fyn-knockout mice was induced by destabilisation of the medial meniscus...
March 19, 2018: Annals of the Rheumatic Diseases
Poorna Subramanian, Sahand Pirbadian, Mohamed Y El-Naggar, Grant J Jensen
Bacterial nanowires have garnered recent interest as a proposed extracellular electron transfer (EET) pathway that links the bacterial electron transport chain to solid-phase electron acceptors away from the cell. Recent studies showed that Shewanella oneidensis MR-1 produces outer membrane (OM) and periplasmic extensions that contain EET components and hinted at their possible role as bacterial nanowires. However, their fine structure and distribution of cytochrome electron carriers under native conditions remained unclear, making it difficult to evaluate the potential electron transport (ET) mechanism along OM extensions...
March 19, 2018: Proceedings of the National Academy of Sciences of the United States of America
Paul P Lin, Alec J Jaeger, Tung-Yun Wu, Sharon C Xu, Abraxa S Lee, Fanke Gao, Po-Wei Chen, James C Liao
The Embden-Meyerhoff-Parnas (EMP) pathway, commonly known as glycolysis, represents the fundamental biochemical infrastructure for sugar catabolism in almost all organisms, as it provides key components for biosynthesis, energy metabolism, and global regulation. EMP-based metabolism synthesizes three-carbon (C3) metabolites before two-carbon (C2) metabolites and must emit one CO2 in the synthesis of the C2 building block, acetyl-CoA, a precursor for many industrially important products. Using rational design, genome editing, and evolution, here we replaced the native glycolytic pathways in Escherichia coli with the previously designed nonoxidative glycolysis (NOG), which bypasses initial C3 formation and directly generates stoichiometric amounts of C2 metabolites...
March 19, 2018: Proceedings of the National Academy of Sciences of the United States of America
Rachel E Bosserman, Cristal Reyna Thompson, Kathleen R Nicholson, Patricia A Champion
Mycobacterium marinum is a non-tuberculous pathogen of poikilothermic fish and an opportunistic human pathogen. Like tuberculous mycobacteria, the M. marinum M strain requires the ESX-1 (ESAT-6 System 1) secretion system for virulence in host cells. EsxB and EsxA, two major virulence factors exported by the ESX-1 system, are encoded by the esxBA genes within the ESX-1 locus. Deletion of the esxBA genes abrogates ESX-1 export and attenuates M. marinum in ex vivo and in vivo models of infection. Interestingly, there are several duplications of the esxB and esxA genes ( esxB_1, esxB_2, esxA_1 , esxA_2, and esxA_3 ) in the M...
March 19, 2018: Journal of Bacteriology
Jeremy T Ritzert, Wyndham W Lathem
Bacterial pathogenesis depends on changes in metabolic and virulence gene expression in response to changes within a pathogen's environment. The plague-causing pathogen, Yersinia pestis, requires expression of the gene encoding the Pla protease for progression of pneumonic plague. The catabolite repressor protein Crp, a global transcriptional regulator, may serve as the activator of pla in response to changes within the lungs as disease progresses. By using gene reporter fusions, the spatial and temporal activation of the crp and pla promoters was measured in a mouse model of pneumonic plague...
March 19, 2018: Journal of Bacteriology
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