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single cell genomics

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https://www.readbyqxmd.com/read/28239471/gene-expression-markers-of-tumor-infiltrating-leukocytes
#1
Patrick Danaher, Sarah Warren, Lucas Dennis, Leonard D'Amico, Andrew White, Mary L Disis, Melissa A Geller, Kunle Odunsi, Joseph Beechem, Steven P Fling
BACKGROUND: Assays of the abundance of immune cell populations in the tumor microenvironment promise to inform immune oncology research and the choice of immunotherapy for individual patients. We propose to measure the intratumoral abundance of various immune cell populations with gene expression. In contrast to IHC and flow cytometry, gene expression assays yield high information content from a clinically practical workflow. Previous studies of gene expression in purified immune cells have reported hundreds of genes showing enrichment in a single cell type, but the utility of these genes in tumor samples is unknown...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28239416/biodegradation-of-alkaline-lignin-by-bacillus-ligniniphilus-l1
#2
Daochen Zhu, Peipei Zhang, Changxiao Xie, Weimin Zhang, Jianzhong Sun, Wei-Jun Qian, Bin Yang
BACKGROUND: Lignin is the most abundant aromatic biopolymer in the biosphere and it comprises up to 30% of plant biomass. Although lignin is the most recalcitrant component of the plant cell wall, still there are microorganisms able to decompose it or degrade it. Fungi are recognized as the most widely used microbes for lignin degradation. However, bacteria have also been known to be able to utilize lignin as a carbon or energy source. Bacillus ligniniphilus L1 was selected in this study due to its capability to utilize alkaline lignin as a single carbon or energy source and its excellent ability to survive in extreme environments...
2017: Biotechnology for Biofuels
https://www.readbyqxmd.com/read/28237401/unraveling-biophysical-interactions-of-radiation-pneumonitis-in-non-small-cell-lung-cancer-via-bayesian-network-analysis
#3
Yi Luo, Issam El Naqa, Daniel L McShan, Dipankar Ray, Ines Lohse, Martha M Matuszak, Dawn Owen, Shruti Jolly, Theodore S Lawrence, Feng-Ming Spring Kong, Randall K Ten Haken
BACKGROUND: In non-small-cell lung cancer radiotherapy, radiation pneumonitis≥grade 2 (RP2) depends on patients' dosimetric, clinical, biological and genomic characteristics. METHODS: We developed a Bayesian network (BN) approach to explore its potential for interpreting biophysical signaling pathways influencing RP2 from a heterogeneous dataset including single nucleotide polymorphisms, micro RNAs, cytokines, clinical data, and radiation treatment plans before and during the course of radiotherapy...
February 22, 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/28237031/single-nucleotide-polymorphisms-may-explain-the-contrasting-phenotypes-of-two-variants-of-a-multidrug-resistant-mycobacterium-tuberculosis-strain
#4
María Mercedes Bigi, Beatriz Lopez, Federico Carlos Blanco, María Del Carmen Sasiain, Silvia De la Barrera, Marcelo A Marti, Ezequiel Jorge Sosa, Darío Augusto Fernández Do Porto, Viviana Ritacco, Fabiana Bigi, Marcelo Abel Soria
Globally, about 4.5% of new tuberculosis (TB) cases are multi-drug-resistant (MDR), i.e. resistant to the two most powerful first-line anti-TB drugs. Indeed, 480,000 people developed MDR-TB in 2015 and 190,000 people died because of MDR-TB. The MDR Mycobacterium tuberculosis M family, which belongs to the Haarlem lineage, is highly prosperous in Argentina and capable of building up further drug resistance without impairing its ability to spread. In this study, we sequenced the whole genomes of a highly prosperous M-family strain (Mp) and its contemporary variant, strain 410, which produced only one recorded tuberculosis case in the last two decades...
March 2017: Tuberculosis
https://www.readbyqxmd.com/read/28236971/ligand-receptor-mediated-regulation-of-growth-in-plants
#5
Miyoshi Haruta, Michael R Sussman
Growth and development of multicellular organisms are coordinately regulated by various signaling pathways involving the communication of inter- and intracellular components. To form the appropriate body patterns, cellular growth and development are modulated by either stimulating or inhibiting these pathways. Hormones and second messengers help to mediate the initiation and/or interaction of the various signaling pathways in all complex multicellular eukaryotes. In plants, hormones include small organic molecules, as well as larger peptides and small proteins, which, as in animals, act as ligands and interact with receptor proteins to trigger rapid biochemical changes and induce the intracellular transcriptional and long-term physiological responses...
2017: Current Topics in Developmental Biology
https://www.readbyqxmd.com/read/28235956/genomic-complexity-and-targeted-genes-in-anaplastic-thyroid-cancer-cell-lines
#6
Eleanor Louise Woodward, Andrea Biloglav, Naveen Ravi, Minjun Yang, Lars Ekblad, Johan Wennerberg, Kajsa Paulsson
Anaplastic thyroid cancer (ATC) is a highly malignant disease with very short median survival times. Few studies have addressed the underlying somatic mutations, and the genomic landscape of ATC thus remains largely unknown. In the present study, we have ascertained copy number aberrations, gene fusions, gene expression patterns, and mutations in early-passage cells from ten newly established ATC cell lines using single nucleotide polymorphism (SNP) array analysis, RNA-sequencing and whole exome sequencing...
February 24, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28235832/one-thousand-somatic-snvs-per-skin-fibroblast-cell-set-baseline-of-mosaic-mutational-load-with-patterns-that-suggest-proliferative-origin
#7
Alexej Abyzov, Livia Tomasini, Bo Zhou, Nikolaos Vasmatzis, Gianfilippo Coppola, Mariangela Amenduni, Reenal Pattni, Michael Wilson, Mark Gerstein, Sherman Weissman, Alexander E Urban, Flora M Vaccarino
Few studies have been conducted to understand post-zygotic accumulation of mutations in cells of the healthy human body. We reprogrammed 32 skin fibroblast cells from families of donors into human induced pluripotent stem cell (hiPSC) lines. The clonal nature of hiPSC lines allows a high-resolution analysis of the genomes of the founder fibroblast cells without being confounded by the artifacts of single cell whole genome amplification. We estimate that on average a fibroblast cell in children has 1,035 mostly benign mosaic SNVs...
February 24, 2017: Genome Research
https://www.readbyqxmd.com/read/28231577/response-evaluation-in-head-and-neck-oncology-definition-and-prediction
#8
T K Hoffmann, P J Schuler, S Laban, R Grässlin, M Beer, A J Beer, U Friebe-Hoffmann, L Bullinger, P Möller, T Wiegel
Curative treatment of head and neck squamous cell carcinoma includes surgery and/or (chemo)radiation, whereas in the palliative setting, chemotherapy and/or immunotherapy represent(s) the standard approach. With regard to quality control, methods for determining treatment response are sorely needed. For surgical therapy, histopathology is the standard quality control. Established criteria for high-risk patients include resection margins of the primary tumor and extracapsular extension of lymph node metastases...
February 24, 2017: ORL; Journal for Oto-rhino-laryngology and its related Specialties
https://www.readbyqxmd.com/read/28229505/a-variant-in-a-cis-regulatory-element-enhances-claudin-14-expression-and-is-associated-with-pediatric-onset-hypercalciuria-and-kidney-stones
#9
Megan E Ure, Emma Heydari, Wanling Pan, Ajay Ramesh, Sabah Rehman, Catherine Morgan, Maury Pinsk, Robin Erickson, Johannes M Herrmann, Henrik Dimke, Emmanuelle Cordat, Mathieu Lemaire, Michael Walter, R Todd Alexander
The greatest risk factor for kidney stones is hypercalciuria, the etiology of which is largely unknown. A recent genome-wide association study (GWAS) linked hypercalciuria and kidney stones to a claudin-14 (CLDN14) risk haplotype. However, the underlying molecular mechanism was not delineated. Recently, renal CLDN14 expression was found to increase in response to increased plasma calcium, thereby inducing calciuria. We hypothesized therefore that some children with hypercalciuria and kidney stones harbor a CLDN14 variant that inappropriately increases gene expression...
February 22, 2017: Human Mutation
https://www.readbyqxmd.com/read/28228523/vpx-overcomes-a-samhd1-independent-block-to-hiv-reverse-transcription-that-is-specific-to-resting-cd4-t-cells
#10
Hanna-Mari Baldauf, Lena Stegmann, Sarah-Marie Schwarz, Ina Ambiel, Maud Trotard, Margarethe Martin, Manja Burggraf, Gina M Lenzi, Helena Lejk, Xiaoyu Pan, Oliver I Fregoso, Efrem S Lim, Libin Abraham, Laura A Nguyen, Frank Rutsch, Renate König, Baek Kim, Michael Emerman, Oliver T Fackler, Oliver T Keppler
Early after entry into monocytes, macrophages, dendritic cells, and resting CD4 T cells, HIV encounters a block, limiting reverse transcription (RT) of the incoming viral RNA genome. In this context, dNTP triphosphohydrolase SAM domain and HD domain-containing protein 1 (SAMHD1) has been identified as a restriction factor, lowering the concentration of dNTP substrates to limit RT. The accessory lentiviral protein X (Vpx) proteins from the major simian immunodeficiency virus of rhesus macaque, sooty mangabey, and HIV-2 (SIVsmm/SIVmac/HIV-2) lineage packaged into virions target SAMHD1 for proteasomal degradation, increase intracellular dNTP pools, and facilitate HIV cDNA synthesis...
February 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28228384/impact-of-disseminated-neuroblastoma-cells-on-the-identification-of-the-relapse-seeding-clone
#11
M Reza Abbasi, Fikret Rifatbegovic, Clemens Brunner, Georg Mann, Andrea Ziegler, Ulrike Pötschger, Roman Crazzolara, Marek Ussowicz, Martin Benesch, Georg Ebetsberger-Dachs, Godfrey Chi-Fung Chan, Neil Jones, Ruth Ladenstein, Inge M Ambros, Peter F Ambros
PURPOSE: Tumor relapse is the most frequent cause of death in stage 4 neuroblastomas. Since genomic information on the relapse precursor cells could guide targeted therapy, our aim was to find the most appropriate tissue for identifying relapse-seeding clones. EXPERIMENTAL DESIGN: We analyzed 10 geographically and temporally separated samples of a single patient by SNP array and validated the data in 154 stage 4 patients. RESULTS: In the case study, aberrations unique to certain tissues and time points were evident besides concordant aberrations shared by all samples...
February 22, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28228136/circulating-tumor-cells-capture-disease-evolution-in-advanced-prostate-cancer
#12
Justin Lack, Marc Gillard, Maggie Cam, Gladell P Paner, David J VanderWeele
BACKGROUND: Genetic analysis of advanced cancer is limited by availability of representative tissue. Biopsies of prostate cancer metastasized to bone are invasive with low quantity of tumor tissue. The prostate cancer genome is dynamic, however, with temporal heterogeneity requiring repeated evaluation as the disease evolves. Circulating tumor cells (CTCs) offer an alternative, "liquid biopsy", though single CTC sequencing efforts are laborious with high failure rates. METHODS: We performed exome sequencing of matched treatment-naïve tumor tissue, castrate resistant tumor tissue, and pooled CTC samples, and compared mutations identified in each...
February 23, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28225830/ex-vivo-activation-of-cd4-t-cells-from-donors-on-suppressive-art-can-lead-to-sustained-production-of-infectious-hiv-1-from-a-subset-of-infected-cells
#13
John K Bui, Elias K Halvas, Elizabeth Fyne, Michele D Sobolewski, Dianna Koontz, Wei Shao, Brian Luke, Feiyu F Hong, Mary F Kearney, John W Mellors
The fate of HIV-infected cells after reversal of proviral latency is not well characterized. Simonetti, et al. recently showed that CD4+ T-cells containing intact proviruses can clonally expand in vivo and produce low-level infectious viremia. We hypothesized that reversal of HIV latency by activation of CD4+ T-cells can lead to the expansion of a subset of virus-producing cells rather than their elimination. We established an ex vivo cell culture system involving stimulation of CD4+ T-cells from donors on suppressive antiretroviral therapy (ART) with PMA/ionomycin (day 1-7), followed by rest (day 7-21), and then repeat stimulation (day 21-28), always in the presence of high concentrations of raltegravir and efavirenz to effectively block new cycles of viral replication...
February 22, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28225754/targeting-a-car-to-the-trac-locus-with-crispr-cas9-enhances-tumour-rejection
#14
Justin Eyquem, Jorge Mansilla-Soto, Theodoros Giavridis, Sjoukje J C van der Stegen, Mohamad Hamieh, Kristen M Cunanan, Ashlesha Odak, Mithat Gönen, Michel Sadelain
Chimeric antigen receptors (CARs) are synthetic receptors that redirect and reprogram T cells to mediate tumour rejection. The most successful CARs used to date are those targeting CD19 (ref. 2), which offer the prospect of complete remission in patients with chemorefractory or relapsed B-cell malignancies. CARs are typically transduced into the T cells of a patient using γ-retroviral vectors or other randomly integrating vectors, which may result in clonal expansion, oncogenic transformation, variegated transgene expression and transcriptional silencing...
February 22, 2017: Nature
https://www.readbyqxmd.com/read/28224622/slc2a3-single-nucleotide-polymorphism-and-duplication-influence-cognitive-processing-and-population-specific-risk-for-attention-deficit-hyperactivity-disorder
#15
Sören Merker, Andreas Reif, Georg C Ziegler, Heike Weber, Ute Mayer, Ann-Christine Ehlis, Annette Conzelmann, Stefan Johansson, Clemens Müller-Reible, Indrajit Nanda, Thomas Haaf, Reinhard Ullmann, Marcel Romanos, Andreas J Fallgatter, Paul Pauli, Tatyana Strekalova, Charline Jansch, Alejandro Arias Vasquez, Jan Haavik, Marta Ribasés, Josep Antoni Ramos-Quiroga, Jan K Buitelaar, Barbara Franke, Klaus-Peter Lesch
BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a common, highly heritable neurodevelopmental disorder with profound cognitive, behavioral, and psychosocial impairments with persistence across the life cycle. Our initial genome-wide screening approach for copy number variants (CNVs) in ADHD implicated a duplication of SLC2A3, encoding glucose transporter-3 (GLUT3). GLUT3 plays a critical role in cerebral glucose metabolism, providing energy for the activity of neurons, which, in turn, moderates the excitatory-inhibitory balance impacting both brain development and activity-dependent neural plasticity...
February 22, 2017: Journal of Child Psychology and Psychiatry, and Allied Disciplines
https://www.readbyqxmd.com/read/28223401/transcriptome-analyses-of-rhesus-monkey-pre-implantation-embryos-reveal-a-reduced-capacity-for-dna-double-strand-break-repair-in-primate-oocytes-and-early-embryos
#16
Xinyi Wang, Denghui Liu, Dajian He, Shengbo Suo, Xian Xia, Xiechao He, Jing-Dong Han, Ping Zheng
Pre-implantation embryogenesis encompasses several critical events including genome reprogramming, zygotic genome activation (ZGA), and cell fate commitment, most of which remain mechanistically unclear in primates. In addition, primates display a high rate of embryo wastage without any clear molecular basis. Understanding the factors involved in genome reprogramming and ZGA will help the generation of induced pluripotent stem cells with high efficiency. Moreover, explaining the molecular basis responsible for embryo wastage in primates will greatly expand our knowledge of species evolution...
February 21, 2017: Genome Research
https://www.readbyqxmd.com/read/28223393/novel-bacterial-topoisomerase-inhibitors-with-potent-broad-spectrum-activity-against-drug-resistant-bacteria
#17
Cédric Charrier, Anne-Marie Salisbury, Victoria J Savage, Thomas Duffy, Emmanuel Moyo, Nathan Chaffer-Malam, Nicola Ooi, Rebecca Newman, Jonathan Cheung, Richard Metzger, David McGarry, Mark Pichowicz, Ralph Sigerson, Ian R Cooper, Gary Nelson, Hayley S Butler, Mark Craighead, Andrew J Ratcliffe, Stuart A Best, Neil R Stokes
The Novel Bacterial Topoisomerase Inhibitor class is an investigational type of antibacterial inhibitor of DNA gyrase and topoisomerase IV that do not have cross-resistance with the quinolones. Here, we report the evaluation of the in vitro properties of a new series of this type of small molecules. Exemplar compounds selectively and potently inhibited the catalytic activities of Escherichia coli DNA gyrase and topoisomerase IV but did not block the DNA breakage-reunion step. Compounds showed broad-spectrum inhibitory activity against a wide range of Gram-positive and Gram-negative pathogens, including biodefence microorganisms, and Mycobacterium tuberculosis No cross-resistance with quinolone-resistant Staphylococcus aureus and E...
February 21, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28223389/analysis-of-serial-isolates-of-mcr-1-positive-escherichia-coli-reveals-a-highly-active-isapl1-transposon
#18
Erik Snesrud, Ana C Ong, Brendan Corey, Yoon I Kwak, Robert Clifford, Todd Gleeson, Shannon Wood, Timothy J Whitman, Emil P Lesho, Mary Hinkle, Patrick Mc Gann
The emergence of the transferable colistin resistance gene mcr-1 is of global concern. The insertion sequence (IS) Apl1 is a key component in the mobilization of this gene, but its role remains poorly understood.Six Escherichia coli were cultured from the same patient over one month in Germany and the USA after a brief hospitalization in Bahrain for an unconnected illness. Four carried mcr-1 by real-time PCR, but two were negative. Two additional mcr-1-negative E. coli were collected during follow-up surveillance nine months later...
February 21, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28222737/dynamic-genome-scale-metabolic-modeling-of-the-yeast-pichia-pastoris
#19
Francisco Saitua, Paulina Torres, José Ricardo Pérez-Correa, Eduardo Agosin
BACKGROUND: Pichia pastoris shows physiological advantages in producing recombinant proteins, compared to other commonly used cell factories. This yeast is mostly grown in dynamic cultivation systems, where the cell's environment is continuously changing and many variables influence process productivity. In this context, a model capable of explaining and predicting cell behavior for the rational design of bioprocesses is highly desirable. Currently, there are five genome-scale metabolic reconstructions of P...
February 21, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28222723/rapid-precise-quantification-of-bacterial-cellular-dimensions-across-a-genomic-scale-knockout-library
#20
Tristan Ursell, Timothy K Lee, Daisuke Shiomi, Handuo Shi, Carolina Tropini, Russell D Monds, Alexandre Colavin, Gabriel Billings, Ilina Bhaya-Grossman, Michael Broxton, Bevan Emma Huang, Hironori Niki, Kerwyn Casey Huang
BACKGROUND: The determination and regulation of cell morphology are critical components of cell-cycle control, fitness, and development in both single-cell and multicellular organisms. Understanding how environmental factors, chemical perturbations, and genetic differences affect cell morphology requires precise, unbiased, and validated measurements of cell-shape features. RESULTS: Here we introduce two software packages, Morphometrics and BlurLab, that together enable automated, computationally efficient, unbiased identification of cells and morphological features...
February 21, 2017: BMC Biology
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