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Jiayong Dong, Fei Teng, Wenyuan Guo, Jinghui Yang, Guoshan Ding, Zhiren Fu
BACKGROUND/AIMS: Long noncoding RNAs (lncRNAs) are aberrantly expressed in multiple malignant tumors involved in tumor growth and metastasis. Accumulating data show that small nucleolar RNA host gene (SNHG) 1/12/20 plays a key role in the progression of hepatocellular carcinoma (HCC). However, the molecular mechanisms by which SNHG8 contributes to HCC remain elusive and merit exploration. METHODS: The association between SNHG8 expression and the clinicopathological characteristics and prognoses in HCC patients was analysed by using qRT-PCR analysis and the data from The Cancer Genome Atlas...
2018: Cellular Physiology and Biochemistry
Imlimaong Aier, Rahul Semwal, Anju Sharma, Pritish Kumar Varadwaj
Pancreatic cancer remains the fourth leading cause of cancer-related death in the world, and will continue to become the number two cause of cancer-related death unless a remarkable breakthrough is achieved. With a slim chance of early diagnosis, surgery can only provide a median survival of 17-23 months. The presence of a dense stroma makes this cancer resilient to chemotherapy, with very few potent inhibitors like nab paclitaxelin available that can work in combination with chemotherapeutic agents. Survival rates, on the one hand, lie at 8...
December 8, 2018: Cancer Epidemiology
Clarissa Gerhauser, Francesco Favero, Thomas Risch, Ronald Simon, Lars Feuerbach, Yassen Assenov, Doreen Heckmann, Nikos Sidiropoulos, Sebastian M Waszak, Daniel Hübschmann, Alfonso Urbanucci, Etsehiwot G Girma, Vladimir Kuryshev, Leszek J Klimczak, Natalie Saini, Adrian M Stütz, Dieter Weichenhan, Lisa-Marie Böttcher, Reka Toth, Josephine D Hendriksen, Christina Koop, Pavlo Lutsik, Sören Matzk, Hans-Jörg Warnatz, Vyacheslav Amstislavskiy, Clarissa Feuerstein, Benjamin Raeder, Olga Bogatyrova, Eva-Maria Schmitz, Claudia Hube-Magg, Martina Kluth, Hartwig Huland, Markus Graefen, Chris Lawerenz, Gervaise H Henry, Takafumi N Yamaguchi, Alicia Malewska, Jan Meiners, Daniela Schilling, Eva Reisinger, Roland Eils, Matthias Schlesner, Douglas W Strand, Robert G Bristow, Paul C Boutros, Christof von Kalle, Dmitry Gordenin, Holger Sültmann, Benedikt Brors, Guido Sauter, Christoph Plass, Marie-Laure Yaspo, Jan O Korbel, Thorsten Schlomm, Joachim Weischenfeldt
Identifying the earliest somatic changes in prostate cancer can give important insights into tumor evolution and aids in stratifying high- from low-risk disease. We integrated whole genome, transcriptome and methylome analysis of early-onset prostate cancers (diagnosis ≤55 years). Characterization across 292 prostate cancer genomes revealed age-related genomic alterations and a clock-like enzymatic-driven mutational process contributing to the earliest mutations in prostate cancer patients. Our integrative analysis identified four molecular subgroups, including a particularly aggressive subgroup with recurrent duplications associated with increased expression of ESRP1, which we validate in 12,000 tissue microarray tumors...
December 10, 2018: Cancer Cell
Amanda Balboni Iniguez, Gabriela Alexe, Emily Jue Wang, Giovanni Roti, Sarvagna Patel, Liying Chen, Samuel Kitara, Amy Conway, Amanda L Robichaud, Björn Stolte, Pratiti Bandopadhayay, Amy Goodale, Sasha Pantel, Yenarae Lee, Dorian M Cheff, Matthew D Hall, Rajarshi Guha, Mindy I Davis, Marie Menard, Nicole Nasholm, William A Weiss, Jun Qi, Rameen Beroukhim, Federica Piccioni, Cory Johannessen, Kimberly Stegmaier
Drug resistance represents a major challenge to achieving durable responses to cancer therapeutics. Resistance mechanisms to epigenetically targeted drugs remain largely unexplored. We used bromodomain and extra-terminal domain (BET) inhibition in neuroblastoma as a prototype to model resistance to chromatin modulatory therapeutics. Genome-scale, pooled lentiviral open reading frame (ORF) and CRISPR knockout rescue screens nominated the phosphatidylinositol 3-kinase (PI3K) pathway as promoting resistance to BET inhibition...
December 10, 2018: Cancer Cell
Duohui Jing, Yizhou Huang, Xiaoyun Liu, Keith C S Sia, Julia C Zhang, Xiaolu Tai, Meng Wang, Cara E Toscan, Hannah McCalmont, Kathryn Evans, Chelsea Mayoh, Rebecca C Poulos, Miriam Span, Jianqing Mi, Chao Zhang, Jason W H Wong, Dominik Beck, John E Pimanda, Richard B Lock
Glucocorticoids play a critical role in the treatment of lymphoid malignancies. While glucocorticoid efficacy can be largely attributed to lymphocyte-specific apoptosis, its molecular basis remains elusive. Here, we studied genome-wide lymphocyte-specific open chromatin domains (LSOs), and integrated LSOs with glucocorticoid-induced RNA transcription and chromatin modulation using an in vivo patient-derived xenograft model of acute lymphoblastic leukemia (ALL). This led to the identification of LSOs critical for glucocorticoid-induced apoptosis...
December 10, 2018: Cancer Cell
Zhiqiang Li, Pedram Razavi, Qing Li, Weiyi Toy, Bo Liu, Christina Ping, Wilson Hsieh, Francisco Sanchez-Vega, David N Brown, Arnaud F Da Cruz Paula, Luc Morris, Pier Selenica, Emily Eichenberger, Ronglai Shen, Nikolaus Schultz, Neal Rosen, Maurizio Scaltriti, Edi Brogi, Jose Baselga, Jorge S Reis-Filho, Sarat Chandarlapaty
Cyclin dependent kinase 4/6 (CDK4/6) inhibitors (CDK4/6i) are effective in breast cancer; however, drug resistance is frequently encountered and poorly understood. We conducted a genomic analysis of 348 estrogen receptor-positive (ER+ ) breast cancers treated with CDK4/6i and identified loss-of-function mutations affecting FAT1 and RB1 linked to drug resistance. FAT1 loss led to marked elevations in CDK6, the suppression of which restored sensitivity to CDK4/6i. The induction of CDK6 was mediated by the Hippo pathway with accumulation of YAP and TAZ transcription factors on the CDK6 promoter...
December 10, 2018: Cancer Cell
Joshua W Russo, Steven P Balk
In this issue of Cancer Cell, Gerhauser et al. analyze early-onset prostate cancers, showing roles for androgen receptor-driven rearrangements, an early APOBEC-driven mutational mechanism, and ESRP1 gene duplication. Through integration of whole-genome, transcriptome, and methylome data, they identify high-risk subgroups and develop an algorithm that may predict molecular evolution.
December 10, 2018: Cancer Cell
Katarina Zmajkovicova, Katalin Menyhart, Yasmina Bauer, Rolf Studer, Berengere Renault, Marie Schnoebelen, Matthias Bolinger, Oliver Nayler, John Gatfield
Idiopathic pulmonary fibrosis (IPF) is a life-threatening progressive disease characterized by loss of alveolar epithelial cells, inflammation and aberrant fibroblast activation. The two currently approved therapies do not halt or reverse tissue remodeling and therefore novel disease modifying mechanisms are needed. Our results describe YAP/TAZ inhibition through IP receptor activation as a novel mechanism that suppresses pro-fibrotic (myo)fibroblast activity. We investigated the anti-fibrotic properties of the selective prostacyclin (IP) receptor agonist ACT-333679 using primary human lung fibroblasts...
December 11, 2018: American Journal of Respiratory Cell and Molecular Biology
Eleni N Tsakiri, Sentiljana Gumeni, Kalliopi K Iliaki, Dimitra Benaki, Konstantinos Vougas, Gerasimos P Sykiotis, Vassilis G Gorgoulis, Emmanuel Mikros, Luca Scorrano, Ioannis P Trougakos
Metazoans viability depends on their ability to regulate metabolic processes and also to respond to harmful challenges by mounting anti-stress responses; these adaptations were fundamental forces during evolution. Central to anti-stress responses are a number of short-lived transcription factors that by functioning as stress sensors mobilize genomic responses aiming to eliminate stressors. We show here that increased expression of nuclear factor erythroid 2-related factor (Nrf2) in Drosophila activated cytoprotective modules and enhanced stress tolerance...
December 10, 2018: Aging Cell
Yusmiati Liau, Ignatius Chua, Martin A Kennedy, Simran Maggo
Angioedema is a rare adverse effect of the commonly used angiotensin converting enzyme inhibitors (ACEi) and is reported to occur with a prevalence of 0.1 - 0.7%. Although most ACEi-induced angioedema (ACEi-A) cases are mild, severe cases requiring intensive care and even resulting in death have been reported in the literature. The mechanisms underlying ACEi-A are not yet fully understood, but bradykinin and/or substance P accumulation resulting from inhibition of ACE, is believed to play a crucial role. ACEi-A occurs at variable frequencies across different racial groups, suggesting a genetic association to the development of ACEi-A...
December 8, 2018: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
Li-Jie Zhang, Cen Yan, Sarah Schouteden, Xiao-Juan Ma, Dong Zhao, Thorsten Peters, Catherine M Verfaillie, Ying-Mei Feng
RATIONALE: Previously we reported that although the HSPC frequency in bone marrow cells (BMC) was comparable between β2-/- and β2+/+ mice, transplantation of β2-/- BMC into lethally irradiated CD45.1 recipient resulted in more myeloid cell production than β2+/+ BMC. OBJECTIVE: To address if integrin β2 deficiency skews granulocyte/macrophage progenitor (GMP) proliferation. METHODS AND RESULTS: FACS analysis demonstrated that GMP frequency and cell number were higher and megakaryocyte/erythrocyte progenitor (MEP) frequency and cell number were lower in β2-/- mice than β2+/+ mice...
December 11, 2018: Stem Cells
Jianting Shi, Chenyi Xue, Wen Liu, Hanrui Zhang
Macrophages play important roles in many diseases. We describe a protocol and the associated resources for the differentiation of human induced pluripotent stem cell-derived macrophages (IPSDM) and their applications in understanding human macrophage physiology and relevant diseases. The protocol uses an embryoid body-based approach with a combination of serum-free condition for hematopoiesis specification, followed by adherent culture with serum and M-CSF for myeloid expansion and macrophage maturation. The protocol produced an almost pure culture of CD45+ /CD18+ macrophages yielding up to 2 × 107 cells per 6-well plate of iPSCs within 24 days, demonstrating high efficiency, purity, and scalability...
December 10, 2018: Current Protocols in Stem Cell Biology
Qingyao Zhu, Hongjie Yang, Peng Cheng, Qian Han
Some lncRNAs can encode small nucleolar RNAs (snoRNAs), called small nucleolar RNA host genes (SNHGs), which exert diverse regulatory effects on cellular processes. In this study, using RNA-seq and survival data in the Cancer Genome Atlas (TCGA)-Liver Hepatocellular Carcinoma (LIHC), we examined the expression profile of some SNHG genes and explored their prognostic value in hepatocellular carcinoma (HCC). Level-3 RNA-sequencing data, the clinicopathological and survival data of patients with primary HCC were downloaded from the UCSC Xena browser (https://xenabrowser...
December 8, 2018: BioFactors
Ana Carolina Tahira, André Rocha Barbosa, Arthur Sant'Anna Feltrin, Vinicius Daguano Gastaldi, Victor Hugo Calegari de Toledo, José Geraldo de Carvalho Pereira, Bianca Cristina Garcia Lisboa, Viviane Neri de Souza Reis, Ana Cecília Feio Dos Santos, Mariana Maschietto, Helena Brentani
The male-biased prevalence of certain neurodevelopmental disorders and the sex-biased outcomes associated with stress exposure during gestation have been previously described. Here, we hypothesized that genes distinctively targeted by only one or both homologous proteins highly conserved across therian mammals, SOX3 and SRY, could induce sexual adaptive changes that result in a differential risk for neurodevelopmental disorders. ChIP-seq/chip data showed that SOX3/SRY gene targets were expressed in different brain cell types in mice...
December 9, 2018: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
Chi-Yang Chiu, Fang Yuan, Bing-Song Zhang, Ao Yuan, Xin Li, Hong-Bin Fang, Kenneth Lange, Daniel E Weeks, Alexander F Wilson, Joan E Bailey-Wilson, Anthony M Musolf, Dwight Stambolian, M'Hamed Lajmi Lakhal-Chaieb, Richard J Cook, Francis J McMahon, Christopher I Amos, Momiao Xiong, Ruzong Fan
We develop linear mixed models (LMMs) and functional linear mixed models (FLMMs) for gene-based tests of association between a quantitative trait and genetic variants on pedigrees. The effects of a major gene are modeled as a fixed effect, the contributions of polygenes are modeled as a random effect, and the correlations of pedigree members are modeled via inbreeding/kinship coefficients. <mml:math xmlns:mml=""> <mml:mi>F</mml:mi> </mml:math> -statistics and χ 2 likelihood ratio test (LRT) statistics based on the LMMs and FLMMs are constructed to test for association...
December 9, 2018: Genetic Epidemiology
Joanne Trinh, Katja Lohmann, Hauke Baumann, Alexander Balck, Max Borsche, Norbert Brüggemann, Leon Dure, Marissa Dean, Jens Volkmann, Sinem Tunc, Jannik Prasuhn, Heike Pawlack, Sophie Imhoff, Christina M Lill, Meike Kasten, Peter Bauer, Arndt Rolfs, Christine Klein
BACKGROUND: Although the genetic load is high in early-onset Parkinson's disease, thorough investigation of the genetic diagnostic yield has yet to be established. The objectives of this study were to assess variants in known genes for PD and other movement disorders and to find new candidates in 50 patients with early-onset PD. METHODS: We searched for variants either within genes listed by the International Parkinson and Movement Disorder Society Task Force on Genetic Nomenclature or rare homozygous variants in novel candidate genes...
December 10, 2018: Movement Disorders: Official Journal of the Movement Disorder Society
Genevieve M Hoopes, John P Hamilton, Joshua C Wood, Eddi Esteban, Asher Pasha, Brieanne Vaillancourt, Nicholas J Provart, C Robin Buell
Maize(Zea mays L.), a model species for genetic studies, is one of the two most important crop species worldwide.The genome sequence of the reference genotype, B73, representative of the stiff stalk heterotic group was recently updated (AGPv4) using long-read sequencing and optical mapping technology. To facilitate the use of AGPv4 and to enable functional genomic studies and association of genotype with phenotype, we determined expression abundances for replicated mRNA-sequencing datasets from 79 tissues and five abiotic/biotic stress treatments revealing 36,207 expressed genes...
December 7, 2018: Plant Journal: for Cell and Molecular Biology
David Gurwitz
No abstract text is available yet for this article.
December 10, 2018: Drug Development Research
Luchen Ruan, Meng Meng, Cong Wang, Lihua Hou
BACKGROUND: The salt tolerant yeast strain C.versatilis usually is added in the high-salt liquid-state soy sauce fermentation. The genome of C.versatilis was sequenced in our previous study, but the reason of high-osmolarity ability was not clear. RESULTS: The 9.7Mbp genome of C.versatilis contained 4711 CDS. C. versatilis was the closest with another yeast Zygosaccharomyces rouxii added in the soy sauce fermentation in the evolutionary relationship. The protein sequence of the whole genome was divided into 4338 groups, accounting for 92...
December 10, 2018: Journal of the Science of Food and Agriculture
Ruying Qin, Juan Li, Hao Li, Yuandi Zhang, Xiaoshuang Liu, Yuxin Miao, Xiuqing Zhang, Pengcheng Wei
The CRISPR- Streptococcus pyogenes Cas9 (SpCas9) system offers a rapid, simple and flexible genome editing approach. However, the targeting scope of the SpCas9 system is limited by the canonical NGG PAM. To broaden the editing range of the CRISPR system, several Cas orthologs recognized different PAM were isolated from diverse microbes and were engineered as powerful genome editing tools in eukaryotic cells (Murovec et al., 2017). One Cas9 ortholog, Staphylococcus aureus Cas9 (SaCas9), has a smaller size and comparable activity compared to SpCas9 (Kleinstiver et al...
December 10, 2018: Plant Biotechnology Journal
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