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https://www.readbyqxmd.com/read/29353230/a-model-of-dormant-emergent-metastatic-breast-cancer-progression-enabling-exploration-of-biomarker-signatures
#1
Amanda M Clark, Manu Kumar, Sarah Wheeler, Carissa Young, Raman Venkataramanan, Donna Stolz, Linda Griffith, Douglas A Lauffenburger, Alan Wells
Breast cancer mortality predominantly results from dormant micrometastases that emerge as fatal outgrowths years after initial diagnosis. In order to gain insights concerning factors associated with emergence of liver metastases, we recreated spontaneous dormancy in an all-human ex vivo hepatic microphysiological system (MPS). Seeding this MPS with small numbers (<0.05% by cell count) of the aggressive MDA-MB-231 breast cancer cell line, two populations formed: actively proliferating ('growing'; EdU+), and spontaneously quiescent ('dormant'; EdU-)...
January 20, 2018: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29352142/fbxl10-contributes-to-the-development-of-diffuse-large-b-cell-lymphoma-by-epigenetically-enhancing-erk1-2-signaling-pathway
#2
Xiujuan Zhao, Xing Wang, Qian Li, Wanbiao Chen, Na Zhang, Yu Kong, Junqiang Lv, Lei Cao, Dan Lin, Xi Wang, Guogang Xu, Xudong Wu
Epigenetic modifiers have emerged as critical factors governing the biology of different cancers. Herein we show that FBXL10 (also called KDM2B or JHDM1B), an important member of Polycomb repressive complexes, is overexpressed in human diffuse large B-cell lymphoma (DLBCL) tissues and the derived cell lines. Knocking down FBXL10 by specific short hairpin RNAs in DLBCL cells inhibits cell proliferation and induces apoptosis in vitro. Moreover, FBXL10 depletion in DLBCL cells abrogates tumor growth in mouse xenograft models...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29351810/identify-down-syndrome-transcriptome-associations-using-integrative-analysis-of-microarray-database-and-correlation-interaction-network
#3
Min Chen, Jiayan Wang, Yingjun Luo, Kailing Huang, Xiaoshun Shi, Yanhui Liu, Jin Li, Zhengfei Lai, Shuya Xue, Haimei Gao, Allen Chen, Dunjin Chen
BACKGROUND: Long non-coding RNAs (lncRNAs) have previously been emerged as key players in a series of biological processes. Dysregulation of lncRNA is correlated to human diseases including neurological disorders. Here, we developed a multi-step bioinformatics analysis to study the functions of a particular Down syndrome-associated gene DSCR9 including the lncRNAs. The method is named correlation-interaction-network (COIN), based on which a pipeline is implemented. Co-expression gene network analysis and biological network analysis results are presented...
January 19, 2018: Human Genomics
https://www.readbyqxmd.com/read/29351172/a-systematic-review-and-meta-analysis-of-genetic-risk-factors-for-neuropathic-pain
#4
Abirami Veluchamy, Harry L Hébert, Weihua Meng, Colin N A Palmer, Blair H Smith
Neuropathic pain (NP) is an increasingly common chronic pain state and a major health burden, affecting approximately 7-10% of the general population. Emerging evidence suggests that genetic factors could partially explain individual susceptibility to NP and the estimated heritability in twins is 37%. The aim of this study was to systematically review and summarize the studies in humans that have investigated the influence of genetic factors associated with NP. We conducted a comprehensive literature search and performed meta-analyses of all the potential genetic variants associated with NP...
January 18, 2018: Pain
https://www.readbyqxmd.com/read/29348664/stress-induced-trbp-phosphorylation-enhances-its-interaction-with-pkr-to-regulate-cellular-survival
#5
Evelyn Chukwurah, Rekha C Patel
Transactivation response element RNA-binding protein (TRBP or TARBP2) initially identified to play an important role in human immunodeficiency virus (HIV) replication also has emerged as a regulator of microRNA biogenesis. In addition, TRBP functions in signaling pathways by negatively regulating the interferon-induced double-stranded RNA (dsRNA)-activated protein kinase (PKR) during viral infections and cell stress. During cellular stress, PKR is activated and phosphorylates the α subunit of the eukaryotic translation factor eIF2, leading to the cessation of general protein synthesis...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29346070/key-pharmacovigilance-stakeholders-experiences-of-direct-patient-reporting-of-adverse-drug-reactions-and-their-prospects-of-future-development-in-the-european-union
#6
P Inácio, A Cavaco, E Allan, M Airaksinen
OBJECTIVES: In the European Union (EU), legislation allows patients to directly report adverse drug reactions (ADRs) to competent authorities. Five years after its implementation, patient reporting is not equal in all countries. This study aimed to explore key stakeholders' perceptions of patient reporting in four EU countries. STUDY DESIGN: Qualitative study design. METHODS: Twelve representatives from national pharmacovigilance centres and/or authorities as well as national pharmaceutical industry bodies in four EU countries participated in the study...
January 12, 2018: Public Health
https://www.readbyqxmd.com/read/29343622/enhanced-preclinical-antitumor-activity-of-m7824-a-bifunctional-fusion-protein-simultaneously-targeting-pd-l1-and-tgf-%C3%AE
#7
Yan Lan, Dong Zhang, Chunxiao Xu, Kenneth W Hance, Bo Marelli, Jin Qi, Huakui Yu, Guozhong Qin, Aroop Sircar, Vivian M Hernández, Molly H Jenkins, Rachel E Fontana, Amit Deshpande, George Locke, Helen Sabzevari, Laszlo Radvanyi, Kin-Ming Lo
Antibodies targeting immune checkpoints are emerging as potent and viable cancer therapies, but not all patients respond to these as single agents. Concurrently targeting additional immunosuppressive pathways is a promising approach to enhance immune checkpoint blockade, and bifunctional molecules designed to target two pathways simultaneously may provide a strategic advantage over the combination of two single agents. M7824 (MSB0011359C) is a bifunctional fusion protein composed of a monoclonal antibody against programmed death ligand 1 (PD-L1) fused to the extracellular domain of human transforming growth factor-β (TGF-β) receptor II, which functions as a "trap" for all three TGF-β isoforms...
January 17, 2018: Science Translational Medicine
https://www.readbyqxmd.com/read/29343476/role-of-macrophage-socs3-in-the-pathogenesis-of-aortic-dissection
#8
Satoko Ohno-Urabe, Hiroki Aoki, Michihide Nishihara, Aya Furusho, Saki Hirakata, Norifumi Nishida, Sohei Ito, Makiko Hayashi, Hideo Yasukawa, Tsutomu Imaizumi, Hidetoshi Akashi, Hiroyuki Tanaka, Yoshihiro Fukumoto
BACKGROUND: Aortic dissection (AD) is a life-threatening medical emergency caused by the abrupt destruction of the intimomedial layer of the aortic walls. Given that previous studies have reported the involvement of proinflammatory cytokine interleukin-6 in AD pathogenesis, we investigated the role of signal transduction and activator of transcription 3 signaling, a downstream pathway of interleukin-6 in macrophages in pathogenesis of AD. METHODS AND RESULTS: We characterized the pathological and molecular events triggered by aortic stress, which can lead to AD...
January 17, 2018: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29343412/implementing-genome-driven-personalized-cardiology-in-clinical-practice
#9
REVIEW
Ares Pasipoularides
Genomics designates the coordinated investigation of a large number of genes in the context of a biological process or disease. It may be long before we attain comprehensive understanding of the genomics of common complex cardiovascular diseases (CVDs) such as inherited cardiomyopathies, valvular diseases, primary arrhythmogenic conditions, congenital heart syndromes, hypercholesterolemia and atherosclerotic heart disease, hypertensive syndromes, and heart failure with preserved/reduced ejection fraction. Nonetheless, as genomics is evolving rapidly, it is constructive to survey now pertinent concepts and breakthroughs...
January 14, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29342010/the-ever-expanding-saga-of-the-proprotein-convertases-and-their-roles-in-body-homeostasis-emphasis-on-novel-proprotein-convertase-subtilisin-kexin-number-9-functions-and-regulation
#10
Nabil G Seidah, Michel Chrétien, Majambu Mbikay
PURPOSE OF REVIEW: The nine members of the proprotein convertase family play major physiological roles during development and in the adult, and their dysregulation leads to various diseases. The primary objective of this article is to review recent findings on the clinical importance of some of these convertases concentrating mostly on PCSK9, the ninth member of the convertase family. This includes the transcriptional and translational regulation of PCSK9, its ability to enhance the degradation of LDL receptor (LDLR), and the implication of PCSK9 in inflammation and sepsis...
January 15, 2018: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/29340148/reducing-unnecessary-culturing-a-systems-approach-to-evaluating-urine-culture-ordering-and-collection-practices-among-nurses-in-two-acute-care-settings
#11
Robert Redwood, Mary Jo Knobloch, Daniela C Pellegrini, Matthew J Ziegler, Michael Pulia, Nasia Safdar
Background: Inappropriate ordering and acquisition of urine cultures leads to unnecessary treatment of asymptomatic bacteriuria (ASB). Treatment of ASB contributes to antimicrobial resistance particularly among hospital-acquired organisms. Our objective was to investigate urine culture ordering and collection practices among nurses to identify key system-level and human factor barriers and facilitators that affect optimal ordering and collection practices. Methods: We conducted two focus groups, one with ED nurses and the other with ICU nurses...
2018: Antimicrobial Resistance and Infection Control
https://www.readbyqxmd.com/read/29339519/evidence-for-convergent-evolution-of-sine-directed-staufen-mediated-mrna-decay
#12
Bronwyn A Lucas, Eitan Lavi, Lily Shiue, Hana Cho, Sol Katzman, Keita Miyoshi, Mikiko C Siomi, Liran Carmel, Manuel Ares, Lynne E Maquat
Primate-specific Alu short interspersed elements (SINEs) as well as rodent-specific B and ID (B/ID) SINEs can promote Staufen-mediated decay (SMD) when present in mRNA 3'-untranslated regions (3'-UTRs). The transposable nature of SINEs, their presence in long noncoding RNAs, their interactions with Staufen, and their rapid divergence in different evolutionary lineages suggest they could have generated substantial modification of posttranscriptional gene-control networks during mammalian evolution. Some of the variation in SMD regulation produced by SINE insertion might have had a similar regulatory effect in separate mammalian lineages, leading to parallel evolution of the Staufen network by independent expansion of lineage-specific SINEs...
January 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29339415/genome-wide-identification-by-transposon-insertion-sequencing-of-escherichia-coli-k1-genes-essential-for-in-vitro-growth-gastrointestinal-colonizing-capacity-and-survival-in-serum
#13
Alex J McCarthy, Richard A Stabler, Peter W Taylor
Escherichia coli K1 strains are major causative agents of invasive disease of the new born. The age dependency of infection can be reproduced in the neonatal rat. Colonization of the small intestine following oral administration of K1 bacteria leads rapidly to invasion of the blood circulation; bacteria that avoid capture by the mesenteric lymphatic system and evade antibacterial mechanisms in the blood may disseminate to cause organ-specific infections such as meningitis. Some E. coli K1 surface constituents, in particular the polysialic acid capsule, are known to contribute to invasive potential but a comprehensive picture of the factors that determine the fully virulent phenotype has not so far emerged...
January 16, 2018: Journal of Bacteriology
https://www.readbyqxmd.com/read/29338072/targeting-her2-in-colorectal-cancer-the-landscape-of-amplification-and-short-variant-mutations-in-erbb2-and-erbb3
#14
Jeffrey S Ross, Marwan Fakih, Siraj M Ali, Julia A Elvin, Alexa B Schrock, James Suh, Jo-Anne Vergilio, Shakti Ramkissoon, Eric Severson, Sugganth Daniel, David Fabrizio, Garrett Frampton, James Sun, Vincent A Miller, Philip J Stephens, Laurie M Gay
BACKGROUND: In contrast to lung cancer, few precision treatments are available for colorectal cancer (CRC). One rapidly emerging treatment target in CRC is ERBB2 (human epidermal growth factor receptor 2 [HER2]). Oncogenic alterations in HER2, or its dimerization partner HER3, can underlie sensitivity to HER2-targeted therapies. METHODS: In this study, 8887 CRC cases were evaluated by comprehensive genomic profiling for genomic alterations in 315 cancer-related genes, tumor mutational burden, and microsatellite instability...
January 16, 2018: Cancer
https://www.readbyqxmd.com/read/29335803/contribution-of-transposable-elements-and-distal-enhancers-to-evolution-of-human-specific-features-of-interphase-chromatin-architecture-in-embryonic-stem-cells
#15
Gennadi V Glinsky
Transposable elements have made major evolutionary impacts on creation of primate-specific and human-specific genomic regulatory loci and species-specific genomic regulatory networks (GRNs). Molecular and genetic definitions of human-specific changes to GRNs contributing to development of unique to human phenotypes remain a highly significant challenge. Genome-wide proximity placement analysis of diverse families of human-specific genomic regulatory loci (HSGRL) identified topologically associating domains (TADs) that are significantly enriched for HSGRL and designated rapidly evolving in human TADs...
January 15, 2018: Chromosome Research
https://www.readbyqxmd.com/read/29334371/cooperative-targeting-of-melanoma-heterogeneity-with-an-axl-antibody-drug-conjugate-and-braf-mek-inhibitors
#16
Julia Boshuizen, Louise A Koopman, Oscar Krijgsman, Aida Shahrabi, Elke Gresnigt- van den Heuvel, Maarten A Ligtenberg, David W Vredevoogd, Kristel Kemper, Thomas Kuilman, Ji-Ying Song, Nora Pencheva, Jens Thing Mortensen, Marnix Geukes Foppen, Elisa A Rozeman, Christian U Blank, Maarten L Janmaat, David Satijn, Esther C W Breij, Daniel S Peeper, Paul W H I Parren
Intratumor heterogeneity is a key factor contributing to therapeutic failure and, hence, cancer lethality. Heterogeneous tumors show partial therapy responses, allowing for the emergence of drug-resistant clones that often express high levels of the receptor tyrosine kinase AXL. In melanoma, AXL-high cells are resistant to MAPK pathway inhibitors, whereas AXL-low cells are sensitive to these inhibitors, rationalizing a differential therapeutic approach. We developed an antibody-drug conjugate, AXL-107-MMAE, comprising a human AXL antibody linked to the microtubule-disrupting agent monomethyl auristatin E...
January 15, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29331615/increased-brain-glucocorticoid-actions-following-social-defeat-in-rats-facilitates-the-long-term-establishment-of-social-subordination
#17
Meltem Weger, Yannick Sevelinges, Jocelyn Grosse, Isabelle Guillot de Suduiraut, Olivia Zanoletti, Carmen Sandi
Social rank is frequently established through aggressive encounters between new conspecifics. Despite increasing evidence suggesting that social rank is critical for the well-being of both humans and animals, knowledge about the factors influencing social rank remain scarce. Stress was previously shown to affect the establishment and maintenance of social hierarchies in rats. Likewise, increasing systemic corticosterone levels post-encounter in the emerging subordinate rat facilitates the long-term establishment of social subordination...
January 10, 2018: Physiology & Behavior
https://www.readbyqxmd.com/read/29330699/accounting-of-ghg-emissions-and-removals-from-forest-management-a-long-road-from-kyoto-to-paris
#18
REVIEW
Joachim H A Krug
BACKGROUND: Forests have always played an important role in agreeing on accounting rules during the past two decades of international climate policy development. Starting from activity-based gross-net accounting of selected forestry activities to mandatory accounting against a baseline-rules have changed quite rapidly and with significant consequences for accounted credits and debits. Such changes have direct consequences on incentives for climate-investments in forestry. There have also been strong arguments not to include forests into the accounting system by considering large uncertainties, procedural challenges and a fear of unearned credits corrupting the overall accounting system, among others...
January 3, 2018: Carbon Balance and Management
https://www.readbyqxmd.com/read/29329719/regulatory-potential-of-the-rna-processing-machinery-implications-for-human-disease
#19
REVIEW
Kirstyn T Carey, Vihandha O Wickramasinghe
Splicing and nuclear export of mRNA are critical steps in the gene expression pathway. While RNA processing factors can perform general, essential functions for intron removal and bulk export of mRNA, emerging evidence highlights that the core RNA splicing and export machineries also display regulatory potential. Here, we discuss recent insights into how this regulatory potential can selectively alter gene expression and regulate important biological processes. We also highlight the participation of RNA processing pathways in the cellular response to DNA damage at multiple levels...
January 9, 2018: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/29328802/case-study-laparoscopic-appendicectomy-requirements-and-human-factors-surrounding-emergency-care
#20
Julie Widdecombe, Mark Owen
The purpose of this case study is to inform practitioners of the requirements for non-scheduled surgery and the legal, professional and ethical issues surrounding emergencies. Areas for learning include the surgical requirements for appendectomy, evaluation of the differences between scheduled and unscheduled care, and consideration of the vital role that human factors play in emergency situations.
May 2017: Journal of Perioperative Practice
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