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Oren Rom, Guan Xu, Yanhong Guo, Yunhao Zhu, Huilun Wang, Jifeng Zhang, Yanbo Fan, Wenying Liang, Haocheng Lu, Yuhao Liu, Michael Aviram, Zhipeng Liu, Seongho Kim, Wanqing Liu, Xueding Wang, Y Eugene Chen, Luis Villacorta
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) and resulting nonalcoholic steatohepatitis (NASH) are reaching global epidemic proportions. Lack of non-invasive diagnostic tools and effective therapies constitute two of the major hurdles for a bona fide treatment and a reversal of NASH progression and/or regression of the disease. Nitro-oleic acid (OA-NO2 ) has been proven effective in multiple experimental models of inflammation and fibrosis. Thus, the potential benefit of in vivo administration of OA-NO2 to treat advanced NAFLD was tested herein in a model of long-term NASH diet-induced liver damage...
February 13, 2019: EBioMedicine
Gustavo Núñez-Acuña, Cristian Gallardo-Escárate
The salmon louse Lepeophtheirus salmonis is a marine ectoparasite that has a detrimental impact on salmon farms. Genomic knowledge of adult stages is critical to understand the reproductive success and lifecycle completion of this species. Here, we report a comprehensive characterization of the L. salmonis miRNome with emphasis on the sex-differences of the parasite. Small-RNA sequencing was conducted on males and females, and mRNA-sequencing was also conducted to identify miRNA-targets at these stages. Based on bioinformatics analyses, 3101 putative miRNAs were found in L...
February 13, 2019: Marine Genomics
Ruth Montalbo, Juan J Lozano, Laura Izquierdo, Mercedes Ingelmo-Torres, Carmen BaÑos, Joan Palou, Antoine G Van der Heijden, Rafael Medina, Joerg Schmidbauer, Aleix Prat, Maria J Ribal, Antonio Alcaraz, Lourdes Mengual
This study aimed to improve our previous urine gene expression classifiers focusing on the detection of non-high-risk non-muscle-invasive bladder cancer (NMIBC), and develop a new classifier able to decrease the frequency of cystoscopies during bladder cancer (BC) patients' surveillance. A total of 597 urines from BC patients, controls and patients in follow-up for BC (PFBC) were included. The study has 3 phases. In the urinary biomarker discovery phase, 84 urines from BC and control patients were retrospectively included and analyzed by RNA sequencing...
February 7, 2019: Translational Research: the Journal of Laboratory and Clinical Medicine
Izuma Nakayama, Eiji Shinozaki, Seiji Sakata, Noriko Yamamoto, Junko Fujisaki, Yusuke Muramatsu, Toru Hirota, Kengo Takeuchi, Shunji Takahashi, Kensei Yamaguchi, Tetsuo Noda
Gastric cancer in young adults has been pointed out to comprise a subgroup associated with distinctive clinicopathological features, including an equal gender distribution, advanced disease and diffuse-type histology. Comprehensive molecular analyses of gastric cancers have led to molecular-based classifications and to specific and effective treatment options available. The molecular traits of gastric cancers in young adults await investigations, which should provide a clue to explore therapeutic strategies...
February 16, 2019: Cancer Science
Xuejing Yang, Yedan Lu, Fuhong He, Fenxia Hou, Caihong Xing, Peiyu Xu, Qian-Fei Wang
Benzene, a widespread environmental pollutant, induces DNA double-strand breaks (DSBs) and DNA repair, which may further lead to oncogenic mutations, chromosomal rearrangements and leukemogenesis. However, the molecular mechanisms underlying benzene-induced DNA repair and carcinogenesis remain unclear. The human osteosarcoma cell line (U2OS/DR-GFP), which carries a GFP-based homologous recombination (HR) repair reporter, was treated with hydroquinone, one of the major benzene metabolites, to identify the potential effects of benzene on DSB HR repair...
February 16, 2019: Carcinogenesis
Bastien Nguyen, David Venet, Matteo Lambertini, Christine Desmedt, Roberto Salgado, Hugo Mark Horlings, Françoise Rothé, Christos Sotiriou
BACKGROUND: Although parity and age at first pregnancy are among the most known extrinsic factors that modulate breast cancer risk, their impact on the biology of subsequent breast cancer has never been explored in depth. Recent data suggest that pregnancy-induced tumor protection is different according to breast cancer subtypes, with parity and young age at first pregnancy being associated with a marked reduction in the risk of developing luminal subtype but not triple negative breast cancer...
February 15, 2019: Breast Cancer Research: BCR
Haisheng Ding, Huiling Zhao, Guanglong Cheng, Yongxin Yang, Xiaofei Wang, Xiaowei Zhao, Yunxia Qi, Dongwei Huang
BACKGROUND: Hair fibre length is an important economic trait of rabbits in fur production. However, molecular mechanisms regulating rabbit hair growth have remained elusive. RESULTS: Here we aimed to characterise the skin traits and gene expression profiles of short-hair and long-hair rabbits by histological and transcriptome analyses. Haematoxylin-eosin staining was performed to observe the histological structure of the skin of short-hair and long-hair rabbits...
February 15, 2019: BMC Genomics
Simone Mayer, Jiadong Chen, Dmitry Velmeshev, Andreas Mayer, Ugomma C Eze, Aparna Bhaduri, Carlos E Cunha, Diane Jung, Arpana Arjun, Emmy Li, Beatriz Alvarado, Shaohui Wang, Nils Lovegren, Michael L Gonzales, Lukasz Szpankowski, Anne Leyrat, Jay A A West, Georgia Panagiotakos, Arturo Alvarez-Buylla, Mercedes F Paredes, Tomasz J Nowakowski, Alex A Pollen, Arnold R Kriegstein
In the developing human neocortex, progenitor cells generate diverse cell types prenatally. Progenitor cells and newborn neurons respond to signaling cues, including neurotransmitters. While single-cell RNA sequencing has revealed cellular diversity, physiological heterogeneity has yet to be mapped onto these developing and diverse cell types. By combining measurements of intracellular Ca2+ elevations in response to neurotransmitter receptor agonists and RNA sequencing of the same single cells, we show that Ca2+ responses are cell-type-specific and change dynamically with lineage progression...
February 7, 2019: Neuron
Renée R C E Schreurs, Martin E Baumdick, Adrian F Sagebiel, Max Kaufmann, Michal Mokry, Paul L Klarenbeek, Nicola Schaltenberg, Fenja L Steinert, Jorik M van Rijn, Agata Drewniak, Sarah-May M L The, Roel Bakx, Joep P M Derikx, Niek de Vries, Willemijn E Corpeleijn, Steven T Pals, Nicola Gagliani, Manuel A Friese, Sabine Middendorp, Edward E S Nieuwenhuis, Konrad Reinshagen, Teunis B H Geijtenbeek, Johannes B van Goudoever, Madeleine J Bunders
Although the fetal immune system is considered tolerogenic, preterm infants can suffer from severe intestinal inflammation, including necrotizing enterocolitis (NEC). Here, we demonstrate that human fetal intestines predominantly contain tumor necrosis factor-α (TNF-α)+ CD4+ CD69+ T effector memory (Tem) cells. Single-cell RNA sequencing of fetal intestinal CD4+ T cells showed a T helper 1 phenotype and expression of genes mediating epithelial growth and cell cycling. Organoid co-cultures revealed a dose-dependent, TNF-α-mediated effect of fetal intestinal CD4+ T cells on intestinal stem cell (ISC) development, in which low T cell numbers supported epithelial development, whereas high numbers abrogated ISC proliferation...
February 5, 2019: Immunity
Olivia Luige, Merita Murtola, Alice Ghidini, Roger Strömberg
Peptide nucleic acid (PNA)-neocuproine conjugates have been shown to efficiently catalyse the cleavage of RNA target sequences in the presence of Cu2+ ions in a site-specific manner. These artificial enzymes are designed to force the formation of a bulge in the RNA target, the sequence of which has been shown to be key to the catalytic activity. Here, we present a further investigation into the action of Cu2+ -dependent PNAzymes with respect to the dependence on bulge composition in 3- and 4-nucleotide bulge systems...
February 14, 2019: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Jiahao Zhang, Huachao Li, Qipeng Wu, Yueming Chen, Yanchao Deng, Zhicheng Yang, Luyong Zhang, Bing Liu
M2-type tumor-associated macrophages (TAMs) infiltration contributes to cancer malignant progression. However, the mechanisms for controlling recruitment and M2 polarization of macrophages by cancer cells are largely unclear. NADPH oxidase 4 (NOX4) is abundantly expressed in non-small cell lung cancer (NSCLC) and mediates cancer progression. NOXs are in close relation with cancer-related inflammation, nevertheless, whether tumoral NOXs influence microenvironmental macrophages remains undentified. This study found that there was a close association between NOX4 expression and macrophage chemotaxis in patients with NSCLC analyzed using TCGA RNA-sequencing data...
February 6, 2019: Redox Biology
Rachel A Minerath, Colleen M Dewey, Duane D Hall, Chad E Grueter
Thyroid hormone (TH) is a key regulator of transcriptional homeostasis in the heart. While hypothyroidism is known to result in adverse cardiac effects, the molecular mechanisms that modulate TH signaling are not completely understood. Mediator is a multiprotein complex that coordinates signal-dependent transcription factors with the basal transcriptional machinery to regulate gene expression. Mediator complex protein, Med13, represses numerous thyroid receptor (TR) response genes in the heart. Further, cardiac-specific overexpression of Med13 in mice that were treated with propylthiouracil (PTU), an inhibitor of the biosynthesis of the active TH, triiodothyronine (T3), resulted in resistance to PTU-dependent decreases in cardiac contractility...
February 12, 2019: Journal of Molecular and Cellular Cardiology
Andrew E Blum, Srividya Venkitachalam, Durgadevi Ravillah, Aruna K Chelluboyina, Ann Marie Kieber-Emmons, Lakshmeswari Ravi, Adam Kresak, Apoorva K Chandar, Sanford D Markowitz, Marcia I Canto, Jean S Wang, Nicholas J Shaheen, Yan Guo, Yu Shyr, Joseph E Willis, Amitabh Chak, Vinay Varadan, Kishore Guda
BACKGROUND & AIMS: Esophageal adenocarcinoma (EAC) is resistant to standard chemoradiation treatments and few targeted therapies are available. We used large-scale tissue profiling and pharmacogenetic analyses to identify deregulated signaling pathways in EAC tissues that might be targeted to slow tumor growth or progression. METHODS: We collected 397 biopsy specimens from patients with EAC and non-malignant Barrett's esophagus (BE), with or without dysplasia...
February 12, 2019: Gastroenterology
Lauren E Higdon, Steven Schaffert, Purvesh Khatri, Jonathan S Maltzman
Recently developed single-cell profiling technologies hold promise to provide new insights including analysis of population heterogeneity and linkage of antigen receptors with gene expression. These technologies produce complex data sets that require knowledge of bioinformatics for appropriate analysis. In this minireview, we discuss several single-cell immune profiling technologies for gene and protein expression, including cytometry by time-of-flight, RNA sequencing, and antigen receptor sequencing, as well as key considerations for analysis that apply to each...
February 15, 2019: American Journal of Transplantation
Marah C Runtsch, Morgan C Nelson, Soh-Hyun Lee, Warren Voth, Margaret Alexander, Ruozhen Hu, Jared Wallace, Charisse Petersen, Vanja Panic, Claudio J Villanueva, Kimberley J Evason, Kaylyn M Bauer, Timothy Mosbruger, Sihem Boudina, Mary Bronner, June L Round, Micah J Drummond, Ryan M O'Connell
Identifying regulatory mechanisms that influence inflammation in metabolic tissues is critical for developing novel metabolic disease treatments. Here, we investigated the role of microRNA-146a (miR-146a) during diet-induced obesity in mice. miR-146a is reduced in obese and type 2 diabetic patients and our results reveal that miR-146a-/- mice fed a high-fat diet (HFD) have exaggerated weight gain, increased adiposity, hepatosteatosis, and dysregulated blood glucose levels compared to wild-type controls. Pro-inflammatory genes and NF-κB activation increase in miR-146a-/- mice, indicating a role for this miRNA in regulating inflammatory pathways...
February 15, 2019: PLoS Genetics
Angela R Stermer, Gerardo Reyes, Susan J Hall, Kim Boekelheide
Testicular histology and semen parameters are considered the gold standards when determining male reproductive toxicity. Ethylene glycol monomethyl ether (EGME) is a testicular toxicant with well-described effects on histopathology and sperm parameters. To compare the predictivity and sensitivity of molecular biomarkers of testicular toxicity to the traditional endpoints, small RNAs in the sperm were analyzed by next generation RNA-sequencing (RNA-seq). Adult rats were exposed to 0, 50, 60, or 75 mg/kg EGME by oral gavage for 5 consecutive days...
February 15, 2019: Toxicological Sciences: An Official Journal of the Society of Toxicology
Jimmy F Zhang, Alex R Paciorkowski, Paul A Craig, Feng Cui
BACKGROUND: Functional characterization of single nucleotide variants (SNVs) involves two steps, the first step is to convert DNA to protein and the second step is to visualize protein sequences with their structures. As massively parallel sequencing has emerged as a leading technology in genomics, resulting in a significant increase in data volume, direct visualization of SNVs together with associated protein sequences/structures in a new user interface (UI) would be a more effective way to assess their potential effects on protein function...
February 15, 2019: BMC Bioinformatics
Patrick R Blackburn, Jaime I Davila, Rory A Jackson, Numrah Fadra, Mazen A Atiq, Beth A Pitel, Asha A Nair, Todd J Van De Walker, Mark G Hessler, Sara K Hovel, Rebecca N Wehrs, Karen J Fritchie, Robert B Jenkins, Kevin C Halling, Katherine B Geiersbach
Primary aneurysmal bone cyst (ABC) is a benign multiloculated cystic lesion of bone that is defined cytogenetically by USP6 gene rearrangements. Rearrangements involving USP6 are promoter swaps, usually generated by fusion of the non-coding upstream exons of different partner genes with exon 1 or 2 of USP6, thus leading to transcriptional upregulation of full-length USP6 coding sequence. Testing for USP6 rearrangements is used diagnostically to distinguish it from secondary ABC and other giant cell-rich primary bone tumors...
February 14, 2019: Genes, Chromosomes & Cancer
Liteng Yang, Xin Liu, Ning Zhang, Lifang Chen, Jingyi Xu, Wencheng Tang
Pulmonary fibrosis is a lethal inflammatory disease. In this study, we aimed to explore the potential-related circular RNAs (circRNAs) and genes that are associated with pulmonary fibrosis. Pulmonary fibrosis rat models were constructed and the fibrosis deposition was detected using hematoxylin and eosin and Masson staining. The differentially expressed circRNAs were obtained through RNA sequencing. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were further performed to uncover the key function and pathways in pulmonary fibrosis...
February 14, 2019: Journal of Cellular Biochemistry
Tracy A Sherwood, Kevan L Main, Dana L Wetzel
Red drum ( Sciaenops ocellatus ) is an estuarine Sciaenid with high commercial value and recreational demand. During the past 50 years, overfishing has caused declines in the population that resulted in the development of red drum commercial and stock enhancement aquaculture fisheries. Despite the potential high economic value in both wild and aquaculture commercial fisheries the availability of transcriptomic data for red drum in public databases is limited. The data here represents the transcriptome profiles of three tissues: liver, testis and head kidney from red drum...
February 2019: Data in Brief
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