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https://www.readbyqxmd.com/read/28817800/tia1-mutations-in-amyotrophic-lateral-sclerosis-and-frontotemporal-dementia-promote-phase-separation-and-alter-stress-granule-dynamics
#1
Ian R Mackenzie, Alexandra M Nicholson, Mohona Sarkar, James Messing, Maria D Purice, Cyril Pottier, Kavya Annu, Matt Baker, Ralph B Perkerson, Aishe Kurti, Billie J Matchett, Tanja Mittag, Jamshid Temirov, Ging-Yuek R Hsiung, Charles Krieger, Melissa E Murray, Masato Kato, John D Fryer, Leonard Petrucelli, Lorne Zinman, Sandra Weintraub, Marsel Mesulam, Julia Keith, Sasha A Zivkovic, Veronica Hirsch-Reinshagen, Raymond P Roos, Stephan Züchner, Neill R Graff-Radford, Ronald C Petersen, Richard J Caselli, Zbigniew K Wszolek, Elizabeth Finger, Carol Lippa, David Lacomis, Heather Stewart, Dennis W Dickson, Hong Joo Kim, Ekaterina Rogaeva, Eileen Bigio, Kevin B Boylan, J Paul Taylor, Rosa Rademakers
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are age-related neurodegenerative disorders with shared genetic etiologies and overlapping clinical and pathological features. Here we studied a novel ALS/FTD family and identified the P362L mutation in the low-complexity domain (LCD) of T cell-restricted intracellular antigen-1 (TIA1). Subsequent genetic association analyses showed an increased burden of TIA1 LCD mutations in ALS patients compared to controls (p = 8.7 × 10(-6)). Postmortem neuropathology of five TIA1 mutations carriers showed a consistent pathological signature with numerous round, hyaline, TAR DNA-binding protein 43 (TDP-43)-positive inclusions...
August 16, 2017: Neuron
https://www.readbyqxmd.com/read/28817799/human-astrocyte-maturation-captured-in-3d-cerebral-cortical-spheroids-derived-from-pluripotent-stem-cells
#2
Steven A Sloan, Spyros Darmanis, Nina Huber, Themasap A Khan, Fikri Birey, Christine Caneda, Richard Reimer, Stephen R Quake, Ben A Barres, Sergiu P Paşca
There is significant need to develop physiologically relevant models for investigating human astrocytes in health and disease. Here, we present an approach for generating astrocyte lineage cells in a three-dimensional (3D) cytoarchitecture using human cerebral cortical spheroids (hCSs) derived from pluripotent stem cells. We acutely purified astrocyte-lineage cells from hCSs at varying stages up to 20 months in vitro using immunopanning and cell sorting and performed high-depth bulk and single-cell RNA sequencing to directly compare them to purified primary human brain cells...
August 16, 2017: Neuron
https://www.readbyqxmd.com/read/28817787/evaluation-of-the-electron-transfer-flavoprotein-etf-as-an-antibacterial-target-in-burkholderia-cenocepacia
#3
Maria S Stietz, Christina Lopez, Osasumwen Osifo, Marcelo Tolmasky, Silvia T Cardona
There are hundreds of essential genes in multidrug resistant bacterial genomes, but only a few of their products are exploited as antibacterial targets. An example is the electron flavoprotein (ETF) which is required for growth and viability in <i>Burkholderia cenocepacia</i>. Here, we evaluated ETF as an antibiotic target for <i>Burkholderia cepacia</i> complex (Bcc). Depletion of the bacterial ETF during infection of <i>Caenorhabditis elegans</i> significantly extended survival of the nematodes, proving that ETF is essential for survival of <i>B...
August 17, 2017: Canadian Journal of Microbiology
https://www.readbyqxmd.com/read/28817735/association-of-gene-expression-with-biomass-content-and-composition-in-sugarcane
#4
Nam V Hoang, Agnelo Furtado, Angela J O'Keeffe, Frederik C Botha, Robert J Henry
About 64% of the total aboveground biomass in sugarcane production is from the culm, of which ~90% is present in fiber and sugars. Understanding the transcriptome in the sugarcane culm, and the transcripts that are associated with the accumulation of the sugar and fiber components would facilitate the modification of biomass composition for enhanced biofuel and biomaterial production. The Sugarcane Iso-Seq Transcriptome (SUGIT) database was used as a reference for RNA-Seq analysis of variation in gene expression between young and mature tissues, and between 10 genotypes with varying fiber content...
2017: PloS One
https://www.readbyqxmd.com/read/28817732/enhanced-inflammation-in-new-zealand-white-rabbits-when-mers-cov-reinfection-occurs-in-the-absence-of-neutralizing-antibody
#5
Katherine V Houser, Andrew J Broadbent, Lisa Gretebeck, Leatrice Vogel, Elaine W Lamirande, Troy Sutton, Kevin W Bock, Mahnaz Minai, Marlene Orandle, Ian N Moore, Kanta Subbarao
The Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic betacoronavirus that was first detected in humans in 2012 as a cause of severe acute respiratory disease. As of July 28, 2017, there have been 2,040 confirmed cases with 712 reported deaths. While many infections have been fatal, there have also been a large number of mild or asymptomatic cases discovered through monitoring and contact tracing. New Zealand white rabbits are a possible model for asymptomatic infection with MERS-CoV. In order to discover more about non-lethal infections and to learn whether a single infection with MERS-CoV would protect against reinfection, we inoculated rabbits with MERS-CoV and monitored the antibody and inflammatory response...
August 17, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28817720/targeting-of-cdk9-with-indirubin-3-monoxime-safely-and-durably-reduces-hiv-viremia-in-chronically-infected-humanized-mice
#6
Sandra Medina-Moreno, Thomas C Dowling, Juan C Zapata, Nhut M Le, Edward Sausville, Joseph Bryant, Robert R Redfield, Alonso Heredia
Successful propagation of HIV in the human host requires entry into a permissive cell, reverse transcription of viral RNA, integration into the human genome, transcription of the integrated provirus, and assembly/release of new virus particles. Currently, there are antiretrovirals against each of these viral steps, except for provirus transcription. An inhibitor of HIV transcription could both increase potency of treatment and suppress drug-resistant strains. Cellular cyclin-dependent kinase 9 (CDK9) serves as a cofactor for the HIV Tat protein and is required for effective transcription of the provirus...
2017: PloS One
https://www.readbyqxmd.com/read/28817702/global-gene-expression-analysis-of-the-response-of-physic-nut-jatropha-curcas-l-to-medium-and-long-term-nitrogen-deficiency
#7
Qi Kuang, Sheng Zhang, Pingzhi Wu, Yaping Chen, Meiru Li, Huawu Jiang, Guojiang Wu
Jatropha curcas L. is an important biofuel plant with excellent tolerance of barren environments. However, studies on the regulatory mechanisms that operate in this plant in response to nitrogen (N) shortage are scarce. In this study, genome-wide transcriptional profiles of the roots and leaves of 8-week old physic nut seedlings were analyzed after 2 and 16 days of N starvation. Enrichment results showed that genes associated with N metabolism, processing and regulation of RNA, and transport predominated among those showing alterations in expression...
2017: PloS One
https://www.readbyqxmd.com/read/28817650/snorna-and-pirna-expression-levels-modified-by-tobacco-use-in-women-with-lung-adenocarcinoma
#8
Natasha Andressa Nogueira Jorge, Gabriel Wajnberg, Carlos Gil Ferreira, Benilton de Sa Carvalho, Fabio Passetti
Lung cancer is one of the most frequent types of cancer worldwide. Most patients are diagnosed at advanced stage and thus have poor prognosis. Smoking is a risk factor for lung cancer, however most smokers do not develop lung cancer while 20% of women with lung adenocarcinoma are non-smokers. Therefore, it is possible that these two groups present differences besides the smoking status, including differences in their gene expression signature. The altered expression patterns of non-coding RNAs in complex diseases make them potential biomarkers for diagnosis and treatment...
2017: PloS One
https://www.readbyqxmd.com/read/28817612/expression-and-functional-implications-of-the-renal-apelinergic-system-in-rodents
#9
Anne-Marie O'Carroll, Sabrine Salih, Philip R Griffiths, Aarifah Bijabhai, Mark A Knepper, Stephen J Lolait
Apelin binds to the G protein-coupled apelin receptor (APJ; gene name aplnr) to modulate diverse physiological systems including cardiovascular function, and hydromineral and metabolic balance. Recently a second endogenous ligand for APJ, named apela, has been discovered. We confirm that apela activates signal transduction pathways (ERK activation) in cells expressing the cloned rat APJ. Previous studies suggest that exogenous apela is diuretic, attributable wholly or in part to an action on renal APJ. Thus far the cellular distribution of apela in the kidney has not been reported...
2017: PloS One
https://www.readbyqxmd.com/read/28817603/expression-of-the-mhc-class-ii-in-triple-negative-breast-cancer-is-associated-with-tumor-infiltrating-lymphocytes-and-interferon-signaling
#10
In Ah Park, Seong-Hye Hwang, In Hye Song, Sun-Hee Heo, Young-Ae Kim, Won Seon Bang, Hye Seon Park, Miseon Lee, Gyungyub Gong, Hee Jin Lee
Tumor-infiltrating lymphocytes (TILs) have been known for their strong prognostic and predictive significance in triple-negative breast cancer (TNBC). Several mechanisms for TIL influx in TNBC have been elucidated. Major histocompatibility complex class II (MHC-II) is an essential component of the adaptive immune system and is generally restricted to the surface of antigen-presenting cells. However, it has been reported that interferon-gamma signaling may induce MHC-II in almost all cell types, including those derived from cancer...
2017: PloS One
https://www.readbyqxmd.com/read/28817345/reverse-transcription-quantitative-polymerase-chain-reaction-for-detection-of-and-differentiation-between-rna-and-dna-of-hiv-1-based-lentiviral-vectors
#11
Melanie Pavlovic, Nina Koehler, Martina Anton, Anna Dinkelmeier, Maren Haase, Thorsten Stellberger, Ulrich Busch, Armin E Baiker
The purpose of the described method is the detection of and differentiation between RNA and DNA of human immunodeficiency virus (HIV)-derived lentiviral vectors (LV) in cell culture supernatants and swab samples. For the analytical surveillance of genetic engineering, operations methods for the detection of the HIV-1-based LV generations are required. Furthermore, for research issues, it is important to prove the absence of LV particles for downgrading experimental settings in terms of the biosafety level. Here, a quantitative polymerase chain reaction method targeting the long terminal repeat U5 subunit and the start sequence of the packaging signal ψ is described...
August 2017: Human Gene Therapy Methods
https://www.readbyqxmd.com/read/28817234/osmium-mediated-4su-to-c-transformation-as-key-to-study-rna-dynamics-by-sequencing-tuc-seq
#12
Christian Riml, Thomas Amort, Dietmar Rieder, Catherina Gasser, Alexandra Lusser, Ronald Micura
To understand the functional roles of RNA in the cell, it is essential to elucidate the dynamics of their production, processing and decay. A recent method for assessing mRNA dynamics is metabolic labeling with 4-thiouridine (4sU), followed by thio-selective attachment of affinity tags. Detection of labeled transcripts by affinity purification and hybridization to microarrays or by deep sequencing then reveals RNA expression levels. Here, we present a novel sequencing method that eliminates affinity purification and allows for direct assessment of 4sU labeled RNA...
August 17, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28817179/autophagy-induction-plays-a-protective-role-against-hypoxic-stress-in-human-dental-pulp-cells
#13
Sam-Young Park, Eun-Gene Sun, Yeonju Lee, Min-Seok Kim, Jae Hyung Kim, Won-Jae Kim, Ji-Yeon Jung
Human dental pulp exposed to hypoxic conditions induces cell death accompanied by autophagy. However, the role of hypoxia-induced autophagy in human dental pulp cells (HDPCs) is unclear. The present study aimed to investigate the role of autophagy in hypoxia-induced apoptosis of HDPCs. Cobalt chloride (CoCl2 ) treated HDPCs, to mimic hypoxic conditions, decreased cell viability. Also, apoptosis-related signal molecules, cleaved caspase-3 and PARP levels, were enhanced in CoCl2 -treated HDPCs. HDPCs exposed to CoCl2 also promoted autophagy, showing upregulated p62 and microtubule-associated protein 1 light chain 3 (LC3)-II levels, typical autophagic markers, and increased acidic autophagolysosomal vacuoles...
August 17, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28817151/comprehensive-analysis-of-long-noncoding-rna-mrna-co-expression-patterns-in-thyroid-cancer
#14
Yaying Du, Wenfei Xia, Jinjun Zhang, Dongyi Wan, Zhifang Yang, Xingrui Li
Novel molecular-targeted treatments show great prospects for radioiodine-refractory and surgically inoperable thyroid carcinomas. While aberrations in protein-coding genes are a focus in molecular thyroid cancer medicine, the impact of oncogenes on the expression of long noncoding RNAs (lncRNAs) has been largely uncharacterized. We aimed to identify the expression patterns of lncRNAs and mRNAs in high-throughput molecular profiles of 18 papillary thyroid cancer (PTC) patients. We identified 452 mRNAs and 240 unannotated lncRNAs that were differentially expressed in PTC...
August 17, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28816938/advanced-glycation-end-products-promote-chrebp-expression-and-cell-proliferation-in-liver-cancer-cells-by-increasing-reactive-oxygen-species
#15
Hanbei Chen, Yakui Li, Yemin Zhu, Lifang Wu, Jian Meng, Ning Lin, Dianqiang Yang, Minle Li, WenJin Ding, Xuemei Tong, Qing Su
The aim of the study was to elucidate the mechanism by which advanced glycation end products (AGEs) promote cell proliferation in liver cancer cells.We treated liver cancer HepG2 cells with 200 mg/L AGEs or bovine serum albumin (BSA) and assayed for cell viability, cell cycle, and apoptosis. We performed real-time PCR and Western blot analysis for RNA and protein levels of carbohydrate responsive element-binding protein (ChREBP) in AGEs- or BSA-treated HepG2 cells. We analyzed the level of reactive oxygen species (ROS) in HepG2 cells treated with AGEs or BSA...
August 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28816721/drop-in-cd4-counts-below-200-cells-%C3%A2%C2%B5l-after-reaching-or-starting-from-values-higher-than-350-cells-%C3%A2%C2%B5l-in-hiv-infected-patients-with-virological-suppression
#16
Nicola Gianotti, Giulia Marchetti, Andrea Antinori, Annalisa Saracino, Andrea Gori, Giuliano Rizzardini, Miriam Lichtner, Alessandra Bandera, Cristina Mussini, Enrico Girardi, Antonella d'Arminio Monforte, Alessandro Cozzi-Lepri
BACKGROUND: Aim of the study was to quantify the risk of a drop in CD4+ counts below 200 cells/µL after reaching values >350 cells/µL on antiretroviral therapy (or after starting antiretroviral therapy with CD4+ count >350 cells/µL) in the absence of virological failure. SETTING: Ambulatory care services, Italy. METHODS: Prospective cohort study of patients enrolled in the ICONA Foundation Study cohort who started ART with >350 CD4+/μL, or with ≤350 CD4+/µL and reached values >350 cells/µL after virological suppression (VS, defined by two consecutive viral loads ≤50 copies/mL)...
August 12, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28816625/possible-roles-of-%C3%AF-dependent-rna-polymerase-pausing-in-transcription-regulation
#17
Ivan Petushkov, Daria Esyunina, Andrey Kulbachinskiy
The σ subunit of bacterial RNA polymerase is required for promoter recognition during transcription initiation but may also regulate transcription elongation. The principal σ(70) subunit of Escherichia coli was shown to travel with RNA polymerase and induce transcriptional pausing at promoter-like motifs, with potential regulatory output. We recently demonstrated that an alternative σ(38) subunit can also induce RNA polymerase pausing. Here, we outline proposed regulatory roles of σ-dependent pausing in bacteria and discuss possible interplay between alternative σ variants and regulatory factors during transcription elongation...
August 17, 2017: RNA Biology
https://www.readbyqxmd.com/read/28816616/transfer-rna-mediated-enhancement-of-ribosomal-proteins-s6-kinases-signalling-for-cell-proliferation
#18
Nam Hoon Kwon, Mi Ran Lee, Jiwon Kong, Seung Kyun Park, Byung Joon Hwang, Byung Gyu Kim, Eun-Shin Lee, Hyeong-Gon Moon, Sunghoon Kim
While transfer RNAs (tRNAs) are known to transport amino acids to ribosome, new functions are being unveiled from tRNAs and their fragments beyond protein synthesis. Here we show that phosphorylation of 90-kDa RPS6K (ribosomal proteins S6 kinase) was enhanced by tRNA(Leu) overexpression under amino acids starvation condition. The phosphorylation of 90-kDa RPS6K was decreased by siRNA specific to tRNA(Leu) and was independent to mTOR (mammalian target of rapamycin) signalling. Among the 90-kDa RPS6K family, RSK1 (ribosomal S6 kinase 1) and MSK2 (mitogen-and stress-activated protein kinase 2) were the major kinases phosphorylated by tRNA(Leu) overexpression...
August 17, 2017: RNA Biology
https://www.readbyqxmd.com/read/28816609/evidence-of-diversity-site-and-host-specificity-of-sea-turtle-blood-flukes-digenea-schistosomatoidea-spirorchiidae-a-molecular-prospecting-study
#19
Brian A Stacy, Phoebe A Chapman, Allen M Foley, Ellis C Greiner, Lawrence H Herbst, Alan B Bolten, Paul A Klein, Charles A Manire, Elliott R Jacobson
Neospirorchis (Digenea: "Spirorchiidae") are blood flukes of sea turtles. Trematodes tentatively identified as Neospirorchis sp. infect various sites within sea turtles inhabiting waters of the southeastern United States, but efforts to obtain specimens adequate for morphologic study has proven difficult. Two genetic targets, the internal transcribed spacer region of the ribosomal RNA gene and the partial mitochrondrial cytochrome c oxidase subunit I gene, were used to investigate potential diversity among parasite specimens collected from stranded sea turtles...
August 17, 2017: Journal of Parasitology
https://www.readbyqxmd.com/read/28816603/analysis-of-the-small-non-protein-coding-rna-profile-of-mouse-spermatozoa-reveals-specific-enrichment-of-pirnas-within-mature-spermatozoa
#20
Kate Hutcheon, Eileen A McLaughlin, Simone J Stanger, Ilana R Bernstein, Matthew D Dun, Andrew L Eamens, Brett Nixon
Post-testicular sperm maturation and storage within the epididymis is a key determinant of gamete quality and fertilization competence. Here we demonstrate that mouse spermatozoa possess a complex small non-protein-coding RNA (sRNA) profile, the composition of which is markedly influenced by their epididymal transit. Thus, although miRNAs are highly represented in the spermatozoa of the proximal epididymis, this sRNA class is largely diminished in mature spermatozoa of the distal epididymis. Coincident with this, a substantial enrichment in Piwi-interacting RNA (piRNA) abundance in cauda spermatozoa was detected...
August 17, 2017: RNA Biology
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