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https://www.readbyqxmd.com/read/28092682/limited-heterogeneity-of-known-driver-gene-mutations-among-the-metastases-of-individual-patients-with-pancreatic-cancer
#1
Alvin P Makohon-Moore, Ming Zhang, Johannes G Reiter, Ivana Bozic, Benjamin Allen, Deepanjan Kundu, Krishnendu Chatterjee, Fay Wong, Yuchen Jiao, Zachary A Kohutek, Jungeui Hong, Marc Attiyeh, Breanna Javier, Laura D Wood, Ralph H Hruban, Martin A Nowak, Nickolas Papadopoulos, Kenneth W Kinzler, Bert Vogelstein, Christine A Iacobuzio-Donahue
The extent of heterogeneity among driver gene mutations present in naturally occurring metastases-that is, treatment-naive metastatic disease-is largely unknown. To address this issue, we carried out 60× whole-genome sequencing of 26 metastases from four patients with pancreatic cancer. We found that identical mutations in known driver genes were present in every metastatic lesion for each patient studied. Passenger gene mutations, which do not have known or predicted functional consequences, accounted for all intratumoral heterogeneity...
January 16, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28092681/genomic-analysis-of-globally-diverse-mycobacterium-tuberculosis-strains-provides-insights-into-the-emergence-and-spread-of-multidrug-resistance
#2
Abigail L Manson, Keira A Cohen, Thomas Abeel, Christopher A Desjardins, Derek T Armstrong, Clifton E Barry, Jeannette Brand, Sinéad B Chapman, Sang-Nae Cho, Andrei Gabrielian, James Gomez, Andreea M Jodals, Moses Joloba, Pontus Jureen, Jong Seok Lee, Lesibana Malinga, Mamoudou Maiga, Dale Nordenberg, Ecaterina Noroc, Elena Romancenco, Alex Salazar, Willy Ssengooba, A A Velayati, Kathryn Winglee, Aksana Zalutskaya, Laura E Via, Gail H Cassell, Susan E Dorman, Jerrold Ellner, Parissa Farnia, James E Galagan, Alex Rosenthal, Valeriu Crudu, Daniela Homorodean, Po-Ren Hsueh, Sujatha Narayanan, Alexander S Pym, Alena Skrahina, Soumya Swaminathan, Martie Van der Walt, David Alland, William R Bishai, Ted Cohen, Sven Hoffner, Bruce W Birren, Ashlee M Earl
Multidrug-resistant tuberculosis (MDR-TB), caused by drug-resistant strains of Mycobacterium tuberculosis, is an increasingly serious problem worldwide. Here we examined a data set of whole-genome sequences from 5,310 M. tuberculosis isolates from five continents. Despite the great diversity of these isolates with respect to geographical point of isolation, genetic background and drug resistance, the patterns for the emergence of drug resistance were conserved globally. We have identified harbinger mutations that often precede multidrug resistance...
January 16, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28092679/genome-wide-analysis-of-p53-regulated-transcription-in-myc-driven-lymphomas
#3
C Tonelli, M J Morelli, A Sabò, A Verrecchia, L Rotta, T Capra, S Bianchi, S Campaner, B Amati
The tumour suppressor p53 is a transcription factor that controls cellular stress responses. Here, we dissected the transcriptional programmes triggered upon restoration of p53 in Myc-driven lymphomas, based on the integrated analysis of p53 genomic occupancy and gene regulation. p53 binding sites were identified at promoters and enhancers, both characterized by the pre-existence of active chromatin marks. Only a small fraction of these sites showed the 20 base-pair p53 consensus motif, suggesting that p53 recruitment to genomic DNA was primarily mediated through protein-protein interactions in a chromatin context...
January 16, 2017: Oncogene
https://www.readbyqxmd.com/read/28092667/oncogenic-braf-fusions-in-mucosal-melanomas-activate-the-mapk-pathway-and-are-sensitive-to-mek-pi3k-inhibition-or-mek-cdk4-6-inhibition
#4
H S Kim, M Jung, H N Kang, H Kim, C-W Park, S-M Kim, S J Shin, S H Kim, S G Kim, E K Kim, M R Yun, Z Zheng, K Y Chung, J Greenbowe, S M Ali, T-M Kim, B C Cho
Despite remarkable progress in cutaneous melanoma genomic profiling, the mutational landscape of primary mucosal melanomas (PMM) remains unclear. Forty-six PMMs underwent targeted exome sequencing of 111 cancer-associated genes. Seventy-six somatic nonsynonymous mutations in 42 genes were observed, and recurrent mutations were noted on eight genes, including TP53 (13%), NRAS (13%), SNX31 (9%), NF1 (9%), KIT (7%) and APC (7%). Mitogen-activated protein kinase (MAPK; 37%), cell cycle (20%) and phosphatidylinositol 3-kinase (PI3K)-mTOR (15%) pathways were frequently mutated...
January 16, 2017: Oncogene
https://www.readbyqxmd.com/read/28092646/ex-vivo-nonviral-gene-delivery-of-%C3%AE-opioid-receptor-to-attenuate-cancer-induced-pain
#5
Seiichi Yamano, Chi T Viet, Dongmin Dang, Jisen Dai, Shigeru Hanatani, Tadahiro Takayama, Hironori Kasai, Kentaro Imamura, Ron Campbell, Yi Ye, John C Dolan, William Myung Kwon, Stefan D Schneider, Brian L Schmidt
Virus-mediated gene delivery shows promise for the treatment of chronic pain. However, viral vectors have cytotoxicity. To avoid toxicities and limitations of virus-mediated gene delivery, we developed a novel nonviral hybrid vector: HIV-1 Tat peptide sequence modified with histidine and cysteine residues combined with a cationic lipid. The vector has high transfection efficiency with little cytotoxicity in cancer cell lines including HSC-3 (human tongue squamous cell carcinoma) and exhibits differential expression in HSC-3 (∼45-fold) relative to HGF-1 (human gingival fibroblasts) cells...
February 2017: Pain
https://www.readbyqxmd.com/read/28092512/a-hidden-markov-model-for-seismocardiography
#6
Johan Wahlstrom, Isaac Skog, Peter Handel, Farzad Khosrow-Khavar, Kouhyar Tavakolian, Phyllis K Stein, Arye Nehorai
We propose a hidden Markov model approach for processing seismocardiograms. The seismocardiogram morphology is learned using the expectation-maximization algorithm, and the state of the heart at a given time instant is estimated by the Viterbi algorithm. From the obtained Viterbi sequence, it is then straightforward to estimate instantaneous heart rate, heart rate variability measures, and cardiac time intervals (the latter requiring a small number of manual annotations). As is shown in the conducted experimental study, the presented algorithm outperforms the state-of-the-art in seismocardiogrambased heart rate and heart rate variability estimation Moreover, the isovolumic contraction time and the left ventricular ejection time are estimated with mean absolute errors of about 5 [ms] and 9 [ms], respectively...
January 9, 2017: IEEE Transactions on Bio-medical Engineering
https://www.readbyqxmd.com/read/28092033/purification-of-socs-suppressor-of-cytokine-signaling-sh2-domains-for-structural-and-functional-studies
#7
Nicholas P D Liau, Artem Laktyushin, Jeffrey J Babon
Src Homology 2 (SH2) domains are protein domains which have a high binding affinity for specific amino acid sequences containing a phosphorylated tyrosine residue. The Suppressors of Cytokine Signaling (SOCS) proteins use an SH2 domain to bind to components of certain cytokine signaling pathways to downregulate the signaling cascade. The recombinantly produced SH2 domains of various SOCS proteins have been used to undertake structural and functional studies elucidating the method of how such targeting occurs...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28091959/genetic-variation-in-mitochondrial-genes-of-the-tick-haemaphysalis-flava-collected-from-wild-hedgehogs-in-china
#8
Zhong-Bo Li, Tian-Yin Cheng, Xing-Li Xu, Lu-Lin Song, Guo-Hua Liu
The tick Haemaphysalis flava (Acari: Ixodidae) is an important ectoparasite, which causes direct damage to their hosts and also acts as a vector of various infectious disease agents in China. Despite its significance, the epidemiology, genetics and biology of H. flava has not been studied in detail. In the present study, the genetic variation in three mitochondrial (mt) DNA regions, namely cytochrome c oxidase subunit 1 (cox1) and NADH dehydrogenase subunit 1 and 4 (nad1 and nad4), was examined in H. flava ticks collected from wild hedgehogs in China...
January 16, 2017: Experimental & Applied Acarology
https://www.readbyqxmd.com/read/28091882/identification-of-some-main-streptococcus-iniae-associated-proteins-relationship
#9
Fatima El Aamri, José Ángel Guillén, Daniel Padilla, Félix Acosta, Fernando Real
The surface-associated proteins play a key role in bacterial physiology and pathogenesis, and are the major targets in the development of new vaccines. These proteins contribute to the adaptation of bacteria to different hosts and environments. To study differences at the genomic level, we first sequenced the whole genome of Streptococcus iniae from fish (IUSA-1 strain) and compared it to Streptococcus iniae from human (9117 strain), revealing a high similitude between both strains. To gain further insights into host- and environment-specific differences, we then studied proteins in silico and by High Performance Liquid Chromatography...
January 14, 2017: Veterinary Research Communications
https://www.readbyqxmd.com/read/28091763/the-prevalence-of-trypanosoma-cruzi-the-causal-agent-of-chagas-disease-in-texas-rodent-populations
#10
Adriana Aleman, Trina Guerra, Troy J Maikis, Matthew T Milholland, Ivan Castro-Arellano, Michael R J Forstner, Dittmar Hahn
Rodent species were assessed as potential hosts of Trypanosoma cruzi, the etiologic agent of Chagas disease, from five sites throughout Texas in sylvan and disturbed habitats. A total of 592 rodents were captured, resulting in a wide taxonomic representation of 11 genera and 15 species. Heart samples of 543 individuals were successfully analyzed by SybrGreen-based quantitative PCR (qPCR) targeting a 166 bp fragment of satellite DNA of T. cruzi. Eight rodents representing six species from six genera and two families were infected with T...
January 13, 2017: EcoHealth
https://www.readbyqxmd.com/read/28091676/hemispherical-platinum%C3%A2-%C3%A2-silver-core%C3%A2-%C3%A2-shell-nanoparticles-for-mirna-detection
#11
Elaine Spain, Kellie Adamson, Mohammad Elshahawy, Isabella Bray, Tia E Keyes, Raymond L Stallings, Robert J Forster
Defects within a self-assembled monolayer (SAM) of dodecanethiol on gold have been used as nucleation sites for the electrodeposition of mushroom shaped platinum nanoparticles (PtNPs). The top surfaces of these PtNPs were then decorated with a layer of silver creating a hemispherical - platinum : silver core : shell nanoparticle (Pt-AgNP). Thiolated probe strand miRNA was then immobilised onto the upper silver surface. These regioselectively modified particles were desorbed by applying a current jump to yield nanoparticles capable of hybridising to a complementary miRNA target with electrocatalysis occurring on the non-functionalized lower surface...
January 16, 2017: Analyst
https://www.readbyqxmd.com/read/28091414/acute-myeloid-leukemia-advancements-in-diagnosis-and-treatment
#12
REVIEW
Meng-Ge Yu, Hu-Yong Zheng
OBJECTIVE: Leukemia is the most common pediatric malignancy and a major cause of morbidity and mortality in children. Among all subtypes, a lack of consensus exists regarding the diagnosis and treatment of acute myeloid leukemia (AML). Patient survival rates have remained modest for the past three decades in AML. Recently, targeted therapy has emerged as a promising treatment. DATA SOURCES: We searched the PubMed database for recently published research papers on diagnostic development, target therapy, and other novel therapies of AML...
2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28090632/identification-of-highly-selective-mmp-14-inhibitory-fabs-by-deep-sequencing
#13
Tyler Lopez, Dong Hyun Nam, Evan Kaihara, Zahid Mustafa, Xin Ge
Matrix metalloproteinase (MMP)-14 is an important target for cancer treatment due to its critical roles in tumor invasion and metastasis. Previous failures of all compound-based broad-spectrum MMP inhibitors in clinical trials suggest that selectivity is the key for a successful therapy. With inherent high specificity, monoclonal antibodies (mAbs) therefore arise as attractive inhibitors able to target the particular MMP of interest. As a routine screening method, enzyme-linked immunosorbent assays (ELISA) have been applied to panned phage libraries for the isolation of mAbs inhibiting MMP-14...
January 16, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/28090276/overexpression-of-recombinant-human-teriparatide-rhpth-1-34-in-escherichia-coli-an-innovative-gene-fusion-approach
#14
Nahid Bakhtiari, Zahra Amini Bayat, Sepideh Sagharidouz, Mohsen Vaez
BACKGROUND: Parathyroid hormone is an 84-amino acid peptide secreted by the parathyroid glands. Its physiological role is maintenance of normal serum calcium level and bone remodeling. Biological activity of this hormone is related to N-terminal 1-34 amino acids. The recombinant form of hormone (1-34) has been approved for treatment of osteoporosis from 2002. In this study, a novel fusion partner has been developed for preparation of high yield recombinant 1-34 amino acids of hPTH. METHODS: Novel nucleotide cassette designed encoding a chimeric fusion protein comprising of a fusion partner consisting of a His-tag in N-terminal, 53 amino acids belong to Escherichia coli (E...
January 2017: Avicenna Journal of Medical Biotechnology
https://www.readbyqxmd.com/read/28090264/drought-stress-induced-changes-of-micrornas-in-diploid-and-autotetraploid-paulownia-tomentosa
#15
Xibing Cao, Guoqiang Fan, Lin Cao, Minjie Deng, Zhenli Zhao, Suyan Niu, Zhe Wang, Yuanlong Wang
Drought stress adversely affects plant productivity. Growth and timber production of Paulownia trees are limited under drought stress. Changes in gene expression patterns and miRNA in different ploidy of Paulownia tomentosa have been investigated. However, the responses of P. tomentosa to drought stress at the microRNA (miRNA) level have not been reported so far. To identify miRNA candidates and their target genes involved in the drought stress response in diploid and tetraploid P. tomentosa, four small RNA and four degradome libraries from diploid and autotetraploid P...
2017: Genes & Genomics
https://www.readbyqxmd.com/read/28089793/eggshell-palaeogenomics-palaeognath-evolutionary-history-revealed-through-ancient-nuclear-and-mitochondrial-dna-from-madagascan-elephant-bird-aepyornis-sp-eggshell
#16
Alicia Grealy, Matthew Phillips, Gifford Miller, M Thomas P Gilbert, Jean-Marie Rouillard, David Lambert, Michael Bunce, James Haile
Palaeognaths, the sister group of all other living birds (neognaths), were once considered to be vicariant relics from the breakup of the Gondwanan supercontinent. However, recent molecular studies instead argue for dispersal of volant ancestors across marine barriers. Resolving this debate hinges upon accurately reconstructing their evolutionary relationships and dating their divergences, which often relies on phylogenetic information from extinct relatives and nuclear genomes. Mitogenomes from the extinct elephant birds of Madagascar have helped inform the palaeognath phylogeny; however, nuclear information has remained unavailable...
January 9, 2017: Molecular Phylogenetics and Evolution
https://www.readbyqxmd.com/read/28089613/high-frequency-of-hepatitis-e-virus-infection-in-swine-from-south-brazil-and-close-similarity-to-human-hev-isolates
#17
Ana Maria Passos-Castilho, Celso Francisco Hernandes Granato
Hepatitis E virus is responsible for acute and chronic liver infections worldwide. Swine hepatitis E virus has been isolated in Brazil, and a probable zoonotic transmission has been described, although data are still scarce. The aim of this study was to investigate the frequency of hepatitis E virus infection in pigs from a small-scale farm in the rural area of Paraná State, South Brazil. Fecal samples were collected from 170 pigs and screened for hepatitis E virus RNA using a duplex real-time RT-PCR targeting a highly conserved 70nt long sequence within overlapping parts of ORF2 and ORF3 as well as a 113nt sequence of ORF2...
January 3, 2017: Brazilian Journal of Microbiology: [publication of the Brazilian Society for Microbiology]
https://www.readbyqxmd.com/read/28089481/recommendations-for-mri-based-contouring-of-gross-tumor-volume-and-organs-at-risk-for-radiation-therapy-of-pancreatic-cancer
#18
H D Heerkens, W A Hall, X A Li, P Knechtges, E Dalah, E S Paulson, C A T van den Berg, G J Meijer, E J Koay, C H Crane, K Aitken, M van Vulpen, B A Erickson
PURPOSE: Local recurrence is a common and morbid event in patients with unresectable pancreatic adenocarcinoma. A more conformal and targeted radiation dose to the macroscopic tumor in nonmetastatic pancreatic cancer is likely to reduce acute toxicity and improve local control. Optimal soft tissue contrast is required to facilitate delineation of a target and creation of a planning target volume with margin reduction and motion management. Magnetic resonance imaging (MRI) offers considerable advantages in optimizing soft tissue delineation and is an ideal modality for imaging and delineating a gross tumor volume (GTV) within the pancreas, particularly as it relates to conformal radiation planning...
October 17, 2016: Practical Radiation Oncology
https://www.readbyqxmd.com/read/28089356/insertions-and-deletions-target-lineage-defining-genes-in-human-cancers
#19
Marcin Imielinski, Guangwu Guo, Matthew Meyerson
Certain cell types function as factories, secreting large quantities of one or more proteins that are central to the physiology of the respective organ. Examples include surfactant proteins in lung alveoli, albumin in liver parenchyma, and lipase in the stomach lining. Whole-genome sequencing analysis of lung adenocarcinomas revealed noncoding somatic mutational hotspots near VMP1/MIR21 and indel hotspots in surfactant protein genes (SFTPA1, SFTPB, and SFTPC). Extrapolation to other solid cancers demonstrated highly recurrent and tumor-type-specific indel hotspots targeting the noncoding regions of highly expressed genes defining certain secretory cellular lineages: albumin (ALB) in liver carcinoma, gastric lipase (LIPF) in stomach carcinoma, and thyroglobulin (TG) in thyroid carcinoma...
January 11, 2017: Cell
https://www.readbyqxmd.com/read/28088902/brain-tumor-segmentation-using-deep-belief-networks-and-pathological-knowledge
#20
Tianming Zhan, Yi Chen, Xunning Hong, Zhenyu Lu, Yunjie Chen
In this paper, we propose an automatic brain tumor segmentation method based on Deep Belief Networks (DBNs) and pathological knowledge. The proposed method is targeted against gliomas (both low and high grade) obtained in multi-sequence magnetic resonance images (MRIs). Firstly, a novel deep architecture is proposed to combine the multi-sequences intensities feature extraction with classification to get the classification probabilities of each voxel. Then, graph cut based optimization is executed on the classification probabilities to strengthen the spatial relationships of voxels...
January 12, 2017: CNS & Neurological Disorders Drug Targets
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