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https://www.readbyqxmd.com/read/29053887/low-foxg1-and-high-olig-2-labelling-indices-define-a-prognostically-favorable-subset-in-idh-mutant-gliomas
#1
Sarah Schäfer, Felix Behling, Marco Skardelly, Marilin Koch, Ines Ott, Frank Paulsen, Ghazaleh Tabatabai, Jens Schittenhelm
AIMS: Previous data suggest that expression of transcription factors FoxG1 and Olig-2 can separate hotspot H3F3A-mutant tumors in pediatric glioma. We evaluated their prognostic potential and feasibility for identifying H3F3A-mutant tumors among IDH-mutant/wildtype gliomas. METHODS: Immunohistochemistry of FoxG1/Olig-2 and ATRX in 471 cases of diffuse gliomas and molecular determination of IDH, H3F3A, MGMT and 1p/19 codeletion status. RESULTS: Mean percentage of FoxG1 positive tumor cells increased from 17% in WHO grade II to over 21% in grade III to 37% in grade IV tumors, while mean Olig-2 indices decreased from 29% to 28% to 17% respectively...
October 20, 2017: Neuropathology and Applied Neurobiology
https://www.readbyqxmd.com/read/29053860/clinicopathological-correlations-in-behavioural-variant-frontotemporal-dementia
#2
David C Perry, Jesse A Brown, Katherine L Possin, Samir Datta, Andrew Trujillo, Anneliese Radke, Anna Karydas, John Kornak, Ana C Sias, Gil D Rabinovici, Maria Luisa Gorno-Tempini, Adam L Boxer, Mary De May, Katherine P Rankin, Virginia E Sturm, Suzee E Lee, Brandy R Matthews, Aimee W Kao, Keith A Vossel, Maria Carmela Tartaglia, Zachary A Miller, Sang Won Seo, Manu Sidhu, Stephanie E Gaus, Alissa L Nana, Jose Norberto S Vargas, Ji-Hye L Hwang, Rik Ossenkoppele, Alainna B Brown, Eric J Huang, Giovanni Coppola, Howard J Rosen, Daniel Geschwind, John Q Trojanowski, Lea T Grinberg, Joel H Kramer, Bruce L Miller, William W Seeley
Accurately predicting the underlying neuropathological diagnosis in patients with behavioural variant frontotemporal dementia (bvFTD) poses a daunting challenge for clinicians but will be critical for the success of disease-modifying therapies. We sought to improve pathological prediction by exploring clinicopathological correlations in a large bvFTD cohort. Among 438 patients in whom bvFTD was either the top or an alternative possible clinical diagnosis, 117 had available autopsy data, including 98 with a primary pathological diagnosis of frontotemporal lobar degeneration (FTLD), 15 with Alzheimer's disease, and four with amyotrophic lateral sclerosis who lacked neurodegenerative disease-related pathology outside of the motor system...
October 6, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29053711/evaluation-of-spoligotyping-snps-and-customised-miru-vntr-combination-for-genotyping-mycobacterium-tuberculosis-clinical-isolates-in-madagascar
#3
Rondroarivelo Rasoahanitralisoa, Niaina Rakotosamimanana, David Stucki, Christophe Sola, Sebastien Gagneux, Voahangy Rasolofo Razanamparany
BACKGROUND: Combining different molecular typing methods for Mycobacterium tuberculosis complex (MTBC) can be a powerful tool for molecular epidemiology-based investigation of TB. However, the current standard method that provides high discriminatory power for such a combination, mycobacterial interspersed repetitive units-variable numbers of tandem repeats typing (MIRU-VNTR), is laborious, time-consuming and often too costly for many resource-limited laboratories. We aimed to evaluate a reduced set of loci for MIRU-VNTR typing in combination with spoligotyping and SNP-typing for routine molecular epidemiology of TB...
2017: PloS One
https://www.readbyqxmd.com/read/29053268/synthesis-pharmacology-and-molecular-modeling-studies-on-6-desoxo-n-methylmorphinans-as-potent-%C3%A2%C2%B5-opioid-receptor-agonists
#4
Maria Dumitrascuta, Tanila Ben Haddou, Elena Guerrieri, Stefan M Noha, Lea Schläfer, Helmut Schmidhammer, Mariana Spetea
Position 6 of the morphinan skeleton plays a key role on the µ-opioid receptor (MOR) activity in vitro and in vivo. We describe the consequence of the 6-carbonyl group deletion in N-methylmorphinan-6-ones 1-4 on ligand-MOR interaction, signaling and antinociception. While 6-desoxo compounds 1a, 2a and 4a show similar profiles to their 6-keto counterparts, the 6-desoxo-14-benzyloxy substituted 3a displays significantly increased MOR binding and agonist potency, and a distinct binding mode than its analogue 3...
October 20, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29053266/structure-activity-relationships-of-new-natural-product-based-diaryloxazoles-with-selective-activity-against-androgen-receptor-positive-breast-cancer-cells
#5
Andrew J Robles, Shelby McCowen, Shengxin Cai, Michaels Glassman, Francisco Ruiz, Robert H Cichewicz, Stanton F McHardy, Susan L Mooberry
Targeted therapies for ER+/PR+ and HER2-amplified breast cancers have improved patient survival, but there are no therapies for triple negative breast cancers (TNBC) that lack expression of estrogen and progesterone receptors (ER/PR), or amplification or overexpression of HER2. Gene expression profiling of TNBC has identified molecular subtypes and representative cell lines. An extract of the Texas native plant Amyris texana was found to have selective activity against MDA-MB-453 cells, a model of the luminal androgen receptor (LAR) subtype of TNBC...
October 20, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29052968/non-steroidal-estrogen-receptor-isoform-selective-biphenyls
#6
Seema Bhatnagar, Anjali Soni, Swati Kaushik, Megha Rikhi, T R Santhosh Kumar, B Jayaram
Estrogen receptor (ER) has been a therapeutic target to treat ER positive breast cancer, most notably by agents known as selective estrogen receptor modulators (SERMs). However, resistance and severe adverse effects of known drugs gave impetus to the search for newer agents with better therapeutic profile. ERα and ERβ are two isoforms sharing 56% identity, and having different physiological functions and expressions in various tissues. Only two residues differ in the active sites of the two isoforms motivating us to design isoform selective ligands...
October 20, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/29052681/thermodynamic-signatures-and-cluster-properties-of-self-assembly-in-systems-with-competing-interactions
#7
Andrew P Santos, Jakub Pe Combining Cedilla Kalski, Athanassios Z Panagiotopoulos
Colloidal particles, amphiphiles and functionalized nanoparticles are examples of systems that frequently exhibit short-range attraction coupled with long-range repulsion. We vary the ratio of attraction and repulsion in a simple isotropic model with competing interactions, using molecular simulations, and observe significant differences in the properties of the self-assembled clusters that form. We report conditions that lead to the self-assembly of clusters of a preferred size, accompanied by a change in the slope of the pressure with respect to density, similar to micelles formed by amphiphilic molecules...
October 20, 2017: Soft Matter
https://www.readbyqxmd.com/read/29052609/neuro-ophthalmic-side-effects-of-molecularly-targeted-cancer-drugs
#8
REVIEW
M T Bhatti, A K S Salama
The past two decades has been an amazing time in the advancement of cancer treatment. Molecularly targeted therapy is a concept in which specific cellular molecules (overexpressed, mutationally activated, or selectively expressed proteins) are manipulated in an advantageous manner to decrease the transformation, proliferation, and/or survival of cancer cells. In addition, increased knowledge of the role of the immune system in carcinogenesis has led to the development of immune checkpoint inhibitors to restore and enhance cellular-mediated antitumor immunity...
October 20, 2017: Eye
https://www.readbyqxmd.com/read/29052505/transcriptome-assembly-in-suaeda-aralocaspica-to-reveal-the-distinct-temporal-gene-mirna-alterations-between-the-dimorphic-seeds-during-germination
#9
Lei Wang, Hong-Ling Wang, Lan Yin, Chang-Yan Tian
BACKGROUND: Dimorphic seeds from Suaeda aralocaspica exhibit different germination behaviors that are thought to be a bet-hedging strategy advantageous in harsh and unpredictable environments. To understand the molecular mechanisms of Suaeda aralocaspica dimorphic seed germination, we applied RNA sequencing and small RNA sequencing for samples collected at three germination stages. RESULTS: A total of 79,414 transcripts were assembled using Trinity, of which 57...
October 19, 2017: BMC Genomics
https://www.readbyqxmd.com/read/29052189/cell-type-specific-profiling-of-chromatin-modifications-and-associated-proteins
#10
Ana Karina Morao, Erwann Caillieux, Vincent Colot, François Roudier
Progression of a cell along a differentiation path is characterized by changes in gene expression profiles. Alterations of these transcriptional programs result from cell type-specific transcription factors that act in a dynamic chromatin environment. Understanding the precise contribution of these molecular factors during the differentiation process requires accessing specific cell types within a developing organ. This chapter describes a streamlined and alternative version of INTACT, a method enabling the isolation of specific cell populations by affinity-purification of tagged nuclei and the subsequent analysis of gene expression, transcription factor binding profiles, as well as chromatin state at a genome-wide scale...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29052182/profiling-developmentally-and-environmentally-controlled-chromatin-reprogramming
#11
Clara Bourbousse, Moussa Benhamed, Fredy Barneche
Dynamic reshuffling of the chromatin landscape is a recurrent theme orchestrated in many, if not all, plant developmental transitions and adaptive responses. Spatiotemporal variations of the chromatin properties on regulatory genes and on structural genomic elements trigger the establishment of distinct transcriptional contexts, which in some instances can epigenetically be inherited. Studies on plant cell plasticity during the differentiation of stem cells, including gametogenesis, or the specialization of vegetative cells in various organs, as well as the investigation of allele-specific gene regulation have long been impaired by technical challenges in generating specific chromatin profiles in complex or hardly accessible cell populations...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29051502/comparative-transcriptomics-reveal-developmental-turning-points-during-embryogenesis-of-a-hemimetabolous-insect-the-damselfly-ischnura-elegans
#12
Sabrina Simon, Sven Sagasser, Edoardo Saccenti, Mercer R Brugler, M Eric Schranz, Heike Hadrys, George Amato, Rob DeSalle
Identifying transcriptional changes during embryogenesis is of crucial importance for unravelling evolutionary, molecular and cellular mechanisms that underpin patterning and morphogenesis. However, comparative studies focusing on early/embryonic stages during insect development are limited to a few taxa. Drosophila melanogaster is the paradigm for insect development, whereas comparative transcriptomic studies of embryonic stages of hemimetabolous insects are completely lacking. We reconstructed the first comparative transcriptome covering the daily embryonic developmental progression of the blue-tailed damselfly Ischnura elegans (Odonata), an ancient hemimetabolous representative...
October 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29051346/data-driven-prioritization-and-review-of-targets-for-molecular-based-theranostic-approaches-in-pancreatic-cancer
#13
Marjory Koller, Elmire Hartmans, Derk Jan A de Groot, Xiao Juan Zhao, Gooitzen Michell van Dam, Wouter Nagengast, Rudolf S N Fehrmann
Molecular targeted therapeutical and imaging strategies directed at aberrant signaling-pathways in pancreatic tumor cells may improve the poor outcome of pancreatic ductal adenocarcinoma (PDA). Therefore, relevant molecular targets need to be identified. Methods: We collected publicly available expression profiles of patient derived normal pancreatic tissue (n = 77) and PDA samples (n = 103). Functional Genomic mRNA (FGmRNA) profiling was applied to predict target upregulation on the protein level. We prioritized these targets based on current status of (pre)-clinical therapeutical and imaging evaluation in PDA...
October 19, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29051230/iphemap-an-atlas-of-phenotype-to-genotype-relationships-of-human-ipsc-models-of-neurological%C3%A2-diseases
#14
Ethan W Hollingsworth, Jacob E Vaughn, Josh C Orack, Chelsea Skinner, Jamil Khouri, Sofia B Lizarraga, Mark E Hester, Fumihiro Watanabe, Kenneth S Kosik, Jaime Imitola
Disease modeling with induced pluripotent stem cells (iPSCs) is creating an abundance of phenotypic information that has become difficult to follow and interpret. Here, we report a systematic analysis of research practices and reporting bias in neurological disease models from 93 published articles. We find heterogeneity in current research practices and a reporting bias toward certain diseases. Moreover, we identified 663 CNS cell-derived phenotypes from 243 patients and 214 controls, which varied by mutation type and developmental stage in vitro We clustered these phenotypes into a taxonomy and characterized these phenotype-genotype relationships to generate a phenogenetic map that revealed novel correlations among previously unrelated genes...
October 19, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/29051215/kinome-and-transcriptome-profiling-reveal-broad-and-distinct-activities-of-erlotinib-sunitinib-and-sorafenib-in-the-mouse-heart-and-suggest-cardiotoxicity-from-combined-signal-transducer-and-activator-of-transcription-and-epidermal-growth-factor-receptor-inhibition
#15
Timothy J Stuhlmiller, Jon S Zawistowski, Xin Chen, Noah Sciaky, Steven P Angus, Sean T Hicks, Traci L Parry, Wei Huang, Ju Youn Beak, Monte S Willis, Gary L Johnson, Brian C Jensen
BACKGROUND: Most novel cancer therapeutics target kinases that are essential to tumor survival. Some of these kinase inhibitors are associated with cardiotoxicity, whereas others appear to be cardiosafe. The basis for this distinction is unclear, as are the molecular effects of kinase inhibitors in the heart. METHODS AND RESULTS: We administered clinically relevant doses of sorafenib, sunitinib (cardiotoxic multitargeted kinase inhibitors), or erlotinib (a cardiosafe epidermal growth factor receptor inhibitor) to mice daily for 2 weeks...
October 19, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29051190/molecular-basis-of-overdominance-at-a-flower-color-locus
#16
Amy M LaFountain, Wenjie Chen, Wei Sun, Shilin Chen, Harry A Frank, Baoqing Ding, Yao-Wu Yuan
Single-gene overdominance is one of the major mechanisms proposed to explain heterosis (i.e., hybrid vigor), the phenomenon that hybrid offspring between two inbred lines or varieties show superior phenotypes to both parents. Although sporadic examples of single-gene overdominance have been reported over the decades, the molecular nature of this phenomenon remains poorly understood and it is unclear whether any generalizable principle underlies the various cases. Through bulk segregant analysis, chemical profiling, and transgenic experiments, we show that loss-of-function alleles of the FLAVONE SYNTHASE (FNS) gene cause overdominance in anthocyanin-based flower color intensity in the monkeyflower species Mimulus lewisii FNS negatively affects flower color intensity by competing with the anthocyanin biosynthetic enzymes for the same substrates, yet positively affects flower color intensity by producing flavones, the colorless co-pigments required for anthocyanin stabilization, leading to enhanced pigmentation in the heterozyote (FNS/fns) relative to both homozygotes (FNS/FNS and fns/fns)...
October 19, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/29051059/first-report-of-the-staphylococcus-aureus-isolate-from-subclinical-bovine-mastitis-in-the-south-of-brazil-harboring-resistance-gene-dfrg-and-transposon-family-tn916-1545
#17
Louise Haubert, Isabela Schneid Kroning, Mariana Almeida Iglesias, Wladimir Padilha da Silva
The aim of this work was to identify at the molecular level the species of coagulase-positive staphylococci isolates from clinical and subclinical bovine mastitis samples in Southern Brazil, and to evaluate the antimicrobial resistance profile, as well as the presence of resistance genes. According to the PCR assay, all 31 isolates were classified as Staphylococcus aureus. The isolates were tested for resistance to penicillin, ampicillin, oxacillin, cefoxitin, cephalothin, ceftiofur, streptomycin, tobramycin, teicoplanin, erythromycin, clindamycin, enrofloxacin, sulfonamide, trimethoprim-sulfamethoxazole, trimethoprim, and tetracycline by the disk diffusion method...
October 16, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/29051008/dna-recombination-defects-in-kuwait-clinical-immunologic-and-genetic-profile
#18
Waleed Al-Herz, Michel J Massaad, Janet Chou, Luigi D Notarangelo, Raif S Geha
Defects in DNA Recombination due to mutations in RAG1/2 or DCLRE1C result in combined immunodeficiency (CID) with a range of disease severity. We present the clinical, immunologic and molecular characteristics of 21 patients with defects in RAG1, RAG2 or DCLRE1C, who accounted for 24% of combined immune deficiency cases in the Kuwait National Primary Immunodeficiency Disorders Registry. The distribution of the patients was as follow: 8 with RAG1 deficiency, 6 with RAG2 deficiency and 7 with DCLRE1C deficiency...
October 16, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29050338/tumor-infiltrating-b-cells-producing-antitumor-active-immunoglobulins-in-resected-hcc-prolong-patient-survival
#19
Stefan M Brunner, Timo Itzel, Christoph Rubner, Rebecca Kesselring, Eva Griesshammer, Matthias Evert, Andreas Teufel, Hans J Schlitt, Stefan Fichtner-Feigl
BACKGROUND & AIMS: The immunological microenvironment of HCC influences patient outcome, however, the role of B cells remains unclear. This study investigated effects of local B-cell infiltration in HCC cohorts on patient survival and immunological and molecular tumor microenvironment. RESULTS: Unsupervised gene expression analysis of full cancer transcriptomes (N=2158) revealed a highly co-regulated immunological cluster in HCC that mainly contained immunoglobulin fragments...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050337/comprehensive-immune-transcriptomic-analysis-in-bladder-cancer-reveals-subtype-specific-immune-gene-expression-patterns-of-prognostic-relevance
#20
Runhan Ren, Kathrin Tyryshkin, Charles H Graham, Madhuri Koti, D Robert Siemens
Recent efforts on genome wide profiling of muscle invasive bladder cancer (MIBC) have led to its classification into distinct genomic and transcriptomic molecular subtypes that exhibit variability in prognosis. Evolving evidence from recent immunotherapy trials has demonstrated the significance of pre-existing tumour immune profiles that could guide treatment decisions. To identify immune gene expression patterns associated with the molecular subtypes, we performed a comprehensive in silico immune transcriptomic profiling, utilizing transcriptomic data from 347 MIBC cases from The Cancer Genome Atlas (TCGA)...
September 19, 2017: Oncotarget
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