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Michael Platten, David A Reardon
Strategies to empower the immune system to successfully attack cancers, including vaccination approaches, adaptive T cell therapies, and immune checkpoint modulators, have recently achieved remarkable success across a spectrum of cancer indications. Nonetheless, with rare exception, only a minority of patients with a given type of cancer respond to an immunotherapeutic when administered as single-agent therapy. Although under extensive laboratory and clinical investigation, the role of these approaches for glioma patients remains to be determined...
February 2018: Seminars in Neurology
Po-Han Chen, Jen-Tsan Chi, Michael Boyce
In metazoans, thousands of intracellular proteins are modified with O-linked β-N-acetylglucosamine (O-GlcNAc) in response to a wide range of stimuli and stresses. In particular, a complex and evolutionarily conserved interplay between O-GlcNAcylation and oxidative stress has emerged in recent years. Here, we review the current literature on the connections between O-GlcNAc and oxidative stress, with a particular emphasis on major signaling pathways, such as KEAP1/NRF2, FOXO, NFκB, p53 and cell metabolism...
March 14, 2018: Glycobiology
Angharad E Green, Alejandro Amézquita, Yvan Le-Marc, Matthew J Bull, Thomas R Connor, Eshwar Mahenthiralingam
Pseudomonas aeruginosa (P. aeruginosa) is a common contaminant associated with product recalls in the home and personal care (HPC) industry. Preservation systems are used to prevent spoilage and protect consumers, but greater knowledge is needed of preservative resistance mechanisms used by P. aeruginosa contaminants. We aimed to identify genetic pathways associated with preservative exposure by using an industrial P. aeruginosa strain and implementing RNA-Seq to understand gene expression changes in response to industry relevant conditions...
March 14, 2018: FEMS Microbiology Letters
Shiqi Luo, Feng He, Junjie Luo, Shengqian Dou, Yirong Wang, Annan Guo, Jian Lu
Transfer RNA-derived small RNAs (tsRNAs) are an emerging class of small RNAs, yet their regulatory roles have not been well understood. Here we studied the molecular mechanisms and consequences of tsRNA-mediated regulation in Drosophila. By analyzing 495 public small RNA libraries, we demonstrate that most tsRNAs are conserved, prevalent and abundant in Drosophila. By carrying out mRNA sequencing and ribosome profiling of S2 cells transfected with single-stranded tsRNA mimics and mocks, we show that tsRNAs recognize target mRNAs through conserved complementary sequence matching and suppress target genes by translational inhibition...
March 14, 2018: Nucleic Acids Research
Joel D Ernst, Amber Cornelius, Ludovic Desvignes, Jacqueline Tavs, Brian A Norris
Infection with M. tuberculosis is associated with inconsistent and incomplete elimination of the bacteria, despite development of antigen-specific T cell responses. One mechanism employed by M. tuberculosis is to limit availability of antigen for activation of CD4 T cells. We examined the utility of systemic administration of epitope peptides to activate pre-existing T cells in mice infected with M. tuberculosis. We found that systemic peptide administration: 1) selectively activates T cells specific for the epitope peptide; 2) loads MHC class II on lung macrophages and dendritic cells; 3) activates CD4 T cells in the lung parenchyma; 4) has little antimycobacterial activity...
March 14, 2018: Journal of Infectious Diseases
Peter V Bozhkov
No abstract text is available yet for this article.
March 14, 2018: Journal of Experimental Botany
Zhanfeng Si, Hui Liu, Jiankun Zhu, Jiedan Chen, Qiong Wang, Lei Fang, Fengkai Gao, Yue Tian, Yali Chen, Lijing Chang, Bingliang Liu, Zegang Han, Baoliang Zhou, Yan Hu, Xianzhong Huang, Tianzhen Zhang
In cotton, the formation of fruiting branches affects both plant architecture and fiber yield. Here, we report map-based cloning of the Gossypium barbadense axillary flowering (GbAF) mutation gene, which causes bolls to be borne directly on the main plant stem, and of the G. hirsutum clustered boll (cl1) mutation gene. Both mutant alleles were found to represent point mutations at the Cl1 locus of the corresponding species, and therefore we propose that the GbAF mutation be referred to as cl1b. These Cl1 loci correspond to homologs of tomato SELF-PRUNING (SP), i...
March 14, 2018: Journal of Experimental Botany
Devin Ancona, Dan York, Robert J Higgins, Danika Bannasch, Peter J Dickinson
Choroid plexus tumors (CPTs) occur spontaneously in humans and dogs providing an opportunity for comparative cross species analysis of common tumor mechanisms. Large scale chromosomal copy number alterations are the hallmark of human CPTs and identification of driver genes within these regions is problematic. Copy number alterations in 12 spontaneous dog CPTs were defined using an Illumina 170 K single nucleotide polymorphism array and were characterized by highly recurrent whole chromosomal losses in up to 100% of cases with few chromosome wide gains...
March 14, 2018: Journal of Neuropathology and Experimental Neurology
Min Young Kim, Ji Sook Kim, Seung Han Son, Chang Su Lim, Hea Young Eum, Dae Hyun Ha, Mi Ae Park, Eun Jung Baek, Buom-Yong Ryu, Ho Chul Kang, Vladimir N Uversky, Chul Geun Kim
During hematopoiesis, red blood cells originate from the hematopoietic stem cell reservoir. Although the regulation of erythropoiesis and globin expression has been intensively investigated, the underlining mechanisms are not fully understood, including the interplay between transcription factors and epigenetic factors. Here, we uncover that the Mbd2-free NuRD chromatin remodeling complex potentiates erythroid differentiation of proerythroblasts via managing functions of the CP2c complexes. We found that both Mbd2 and Mbd3 expression is downregulated during differentiation of MEL cells in vitro and in normal erythropoiesis in mouse bone marrow, and Mbd2 downregulation is crucial for erythropoiesis...
March 14, 2018: Nucleic Acids Research
Samuel J Watson, Robert G Sowden, Paul Jarvis
The chloroplast houses photosynthesis in all green plants, and is therefore of fundamental importance to the viability and productivity of plants, ecosystems, and agriculture. Chloroplasts are, however, extremely vulnerable to environmental stress, on account of the inherent volatility of oxygenic photosynthesis. To counteract this sensitivity, sophisticated systems of chloroplast stress acclimation have evolved, and many of these involve broad proteome changes. Here, we provide an overview of the interlocking and mutually dependent mechanisms of abiotic stress-induced chloroplast proteome remodelling...
March 14, 2018: Journal of Experimental Botany
Gaby Aphram, Laurent De Kerchove, Stefano Mastrobuoni, Emiliano Navarra, Silvia Solari, Saadallah Tamer, Jerome Baert, Alain Poncelet, Jean Rubay, Parla Astarci, Philippe Noirhomme, Gebrine El Khoury
OBJECTIVES: Mitral valve (MV) repair is the gold standard for treatment of degenerative mitral regurgitation. A variety of surgical techniques allow surgeons to achieve a high rate of MV repair even with MV diseases of other aetiologies. However, a certain number of repairs fail over time. The aim of this study was to review our single-centre experience of MV re-repair and analyse the mode of repair failure, re-repair safety and efficiency in relation to the initial aetiology. METHODS: Between 1997 and 2015, 91 patients underwent redo MV re-repair...
March 14, 2018: European Journal of Cardio-thoracic Surgery
Jiang He, Yuzu Zhao, Erhu Zhao, Xianxing Wang, Zhen Dong, Yibiao Chen, Liqun Yang, Hongjuan Cui
Background: The cancer-testis specific gene Opa interacting protein 5 (OIP5) is a testis-specific gene that is reactivated in many human cancers, but its functions in glioblastoma remain unclear. Here, we assessed the significance of OIP5 in the tumorigenesis and metastasis of glioblastoma for the first time. Methods: An immunohistochemistry assay was performed to detect OIP5 expression changes in glioblastoma patients. Overall survival analysis was performed to evaluate the prognostic significance of OIP5...
March 14, 2018: Neuro-oncology
Thorsten Tjardes, Markus Luecking
Introduction: To achieve the aim of zero preventable deaths on the battlefield a deeper understanding of uncontrolled hemorrhage from junctional or proximal extremity sources is mandatory. While tourniquet application to the extremities has drastically reduced morbidity and mortality, there is still room for improvement regarding the timing of tourniquet placement as the available evidence clearly points out a tight correlation between timing of tourniquet application and outcome. To save as many lives as possible the "point of no return" regarding the circulatory breakdown due to hemorrhage, colloquially addressed as platinum 5 min, needs to be determined...
March 14, 2018: Military Medicine
Bríd M Ryan
Compared with all other racial and ethnic groups in the U.S., African Americans are disproportionally affected by lung cancer, both in terms of incidence and survival. It is likely that smoking, as the main etiological factor associated with lung cancer, contributes to these disparities, but the precise mechanism is still unclear. This paper seeks to explore the history of lung cancer disparities and review to the literature regarding the various factors that contribute to them.
March 14, 2018: Carcinogenesis
Konstadinos Plestis, Oleg Orlov, Vishal N Shah, Joshua Wong, Matthew Thomas, Alon Aharon, Cinthia Orlov, Georgia Panagopoulos, Scott Goldman
OBJECTIVES: Minimally invasive aortic valve replacement (MIAVR) can be technically demanding and may lead to prolonged operative time. We evaluated the intraoperative and postoperative patient outcomes following implementation of 2 facilitating technologies (FT) in MIAVR: the Cor-Knot titanium fastener and Custodiol-histidine-tryptophan-ketoglutarate solution. METHODS: A total of 299 patients underwent MIAVR from 2008 to 2016; 172 (57.5%) patients were included in the FT group and 127 (42...
March 14, 2018: Interactive Cardiovascular and Thoracic Surgery
Lisette Wintgens, Aleksandr Romanov, Karen Phillips, Gabriel Ballesteros, Martin Swaans, Richard Folkeringa, Ignacio Garcia-Bolao, Evgeny Pokushalov, Lucas Boersma
Aims: Long-term freedom from atrial fibrillation (AF) after catheter ablation (CA) and consequently the potential for stroke reduction remain unpredictable. Percutaneous left atrial appendage closure (LAAC) is an effective mechanical alternative to oral anticoagulation (OAC) for stroke prevention in AF patients. This study aims to evaluate long-term clinical results of combined CA and LAAC in one single procedure. Methods and results: Patients with non-valvular AF who underwent combined CA and LAAC procedure were included in the retrospective compilation of independent prospective general LAAC registries at the individual centres...
March 13, 2018: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
Clément Niel, Christine Sinoquet, Christian Dina, Ghislain Rocheleau
Motivation: Large scale genome-wide association studies (GWAS) are tools of choice for discovering associations between genotypes and phenotypes. To date, many studies rely on univariate statistical tests for association between the phenotype and each assayed single nucleotide polymorphism (SNP). However, interaction between SNPs, namely epistasis, must be considered when tackling the complexity of underlying biological mechanisms. Epistasis analysis at large scale entails a prohibitive computational burden when addressing the detection of more than two interacting SNPs...
March 14, 2018: Bioinformatics
Yue Guo, Renyi Wu, John M Gaspar, Davit Sargsyan, Zheng-Yuan Su, Chengyue Zhang, Linbo Gao, David Cheng, Wenji Li, Chao Wang, Ran Yin, Mingzhu Fang, Michael P Verzi, Ronald P Hart, Ah-Ng Kong
Inflammation is highly associated with colon carcinogenesis. Epigenetic mechanisms could play an important role in the initiation and progression of colon cancer. Curcumin, a dietary phytochemical, shows promising effects in suppressing colitis-associated colon cancer in AOM-DSS mice. However, the potential epigenetic mechanisms of curcumin in colon cancer remain unknown. In this study, the anti-cancer effect of curcumin in suppressing colon cancer in an 18-week AOM-DSS colon cancer mouse model was confirmed...
March 14, 2018: Carcinogenesis
Tristan Pascart, Frédéric Lioté
This review article summarizes the relevant English literature on gout from 2010 through April 2017. It emphasizes that the current epidemiology of gout indicates a rising prevalence worldwide, not only in Western countries but also in Southeast Asia, in close relationship with the obesity and metabolic syndrome epidemics. New pathogenic mechanisms of chronic hyperuricaemia focus on the gut (microbiota, ABCG2 expression) after the kidney. Cardiovascular and renal comorbidities are the key points to consider in terms of management...
March 13, 2018: Rheumatology
Yilun Deng, Yuejuan Qin, Subramanya Srikantan, Anqi Luo, Zi-Ming Cheng, Shahida K Flores, Kris S Vogel, Exing Wang, Patricia L M Dahia
The TMEM127 tumor suppressor gene encodes a transmembrane protein of unknown function mutated in pheochromocytomas and, rarely, in renal cancers. Tumors with inactivating TMEM127 mutations have increased mTORC1 signaling by undefined mechanisms. Here we report that TMEM127 interacts with the lysosome-anchored complex comprised of Rag GTPases, the LAMTOR pentamer (or 'ragulator') and vATPase, which controls amino acid-mediated mTORC1 activation. We found that in nutrient-rich conditions TMEM127 expression reduces mTORC1 recruitment to Rags...
March 14, 2018: Human Molecular Genetics
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