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https://www.readbyqxmd.com/read/28645172/the-biogenesis-pathway-of-trna-derived-pirnas-in-bombyx-germ-cells
#1
Shozo Honda, Takuya Kawamura, Phillipe Loher, Keisuke Morichika, Isidore Rigoutsos, Yohei Kirino
Transfer RNAs (tRNAs) function in translational machinery and further serves as a source of short non-coding RNAs (ncRNAs). tRNA-derived ncRNAs show differential expression profiles and play roles in many biological processes beyond translation. Molecular mechanisms that shape and regulate their expression profiles are largely unknown. Here, we report the mechanism of biogenesis for tRNA-derived Piwi-interacting RNAs (td-piRNAs) expressed in Bombyx BmN4 cells. In the cells, two cytoplasmic tRNA species, tRNAAspGUC and tRNAHisGUG, served as major sources for td-piRNAs, which were derived from the 5΄-part of the respective tRNAs...
June 22, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28645146/analysis-of-in-vitro-evolution-reveals-the-underlying-distribution-of-catalytic-activity-among-random-sequences
#2
Abe Pressman, Janina E Moretti, Gregory W Campbell, Ulrich F Müller, Irene A Chen
The emergence of catalytic RNA is believed to have been a key event during the origin of life. Understanding how catalytic activity is distributed across random sequences is fundamental to estimating the probability that catalytic sequences would emerge. Here, we analyze the in vitro evolution of triphosphorylating ribozymes and translate their fitnesses into absolute estimates of catalytic activity for hundreds of ribozyme families. The analysis efficiently identified highly active ribozymes and estimated catalytic activity with good accuracy...
June 21, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28645115/a-comprehensive-review-of-heregulins-her3-and-her4-as-potential-therapeutic-targets-in-cancer
#3
REVIEW
Jose Mauricio Mota, Katharine Ann Collier, Ricardo Lima Barros Costa, Timothy Taxter, Aparna Kalyan, Caio A Leite, Young Kwang Chae, Francis J Giles, Benedito A Carneiro
Heregulins (HRGs) bind to the receptors HER3 or HER4, induce receptor dimerization, and trigger downstream signaling that leads to tumor progression and resistance to targeted therapies. Increased expression of HRGs has been associated with worse clinical prognosis; therefore, attempts to block HRG-dependent tumor growth have been pursued. This manuscript summarizes the function and signaling of HRGs and review the preclinical evidence of its involvement in carcinogenesis, prognosis, and treatment resistance in several malignancies such as colorectal cancer, non-small cell lung cancer, ovarian cancer, and breast cancer...
June 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28644973/il-18-il-15-il-12-synergy-induces-elevated-and-prolonged-ifn-%C3%AE-production-by-ex-vivo-expanded-nk-cells-which-is-not-due-to-enhanced-stat4-activation
#4
Evan Lusty, Sophie M Poznanski, Karen Kwofie, Talveer S Mandur, Dean A Lee, Carl D Richards, Ali A Ashkar
The synergistic effect of IL-18/IL-15/IL-12 stimulation potently activates NK cells, inducing high levels of IFN-γ production. As a result of this potent stimulatory effect, NK cell pre-activation with IL-18/IL-15/IL-12 is being developed as a cancer immunotherapy. Ex vivo expansion of NK cells enables the efficient generation of large numbers of NK cells for wide-scale and repeated therapeutic use, and is thus an important source of NK cells for clinical application. However, the effects of IL-18/IL-15/IL-12 stimulation on ex vivo expanded NK cells have not yet been assessed...
June 20, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28644958/translating-cancer-epigenomics-into-the-clinic-focus-on-lung-cancer
#5
REVIEW
Josep Mari-Alexandre, Angel Diaz-Lagares, Maria Villalba, Oscar Juan, Ana B Crujeiras, Alfonso Calvo, Juan Sandoval
Epigenetic deregulation is increasingly being recognized as a hallmark of cancer. Recent studies have identified many new epigenetic biomarkers, some of which are being introduced into clinical practice for diagnosis, molecular classification, prognosis or prediction of response to therapies. O-6-methylguanine-DNA methyltransferase gene is the most clinically advanced epigenetic biomarker as it predicts the response to temozolomide and carmustine in gliomas. Therefore, epigenomics may represent a novel and promising tool for precision medicine, and in particular, the detection of epigenomic biomarkers in liquid biopsies will be of great interest for monitoring diseases in patients...
June 2, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28644880/o-glcnacylation-mediates-the-control-of-cytosolic-phosphoenolpyruvate-carboxykinase-activity-via-pgc1%C3%AE
#6
Pedro Latorre, Luis Varona, Carmen Burgos, José A Carrodeguas, Pascual López-Buesa
PGC1α is a coactivator of many transcription factors and cytosolic phosphoenolpyruvate carboxykinase (PCK1) is a key enzyme for gluconeogenesis. PGC1α interacts with the transcription factor PPARγ to stimulate PCK1 expression and thus de novo glucose synthesis. These proteins are not only important for central energy metabolism but also for supplying intermediates for other metabolic pathways, including lipidogenesis and protein synthesis and might therefore be important factors in the ethiopathogenesis of metabolic disorders like diabetes but also in other pathologies like cancer...
2017: PloS One
https://www.readbyqxmd.com/read/28644819/quantifying-the-accuracy-and-precision-of-a-novel-real-time-6-degree-of-freedom-kilovoltage-intrafraction-monitoring-kim-target-tracking-system
#7
J-H Kim, D T Nguyen, C-Y Huang, T Fuangrod, V Caillet, R O'Brien, P Poulsen, J Booth, P Keall
Target rotation can considerably impact the delivered radiotherapy dose depending on the tumour shape. More accurate tumour pose during radiotherapy treatment can be acquired through tracking in 6 degrees-of-freedom (6 DoF) rather than in translation only. A novel real-time 6 DoF kilovoltage intrafraction monitoring (KIM) target tracking system has recently been developed. In this study, we experimentally evaluated the accuracy and precision of the 6 DoF KIM implementation. Real-time 6 DoF KIM motion measurements were compared against the ground truth motion retrospectively derived from kV/MV triangulation for a range of lung and prostate tumour motion trajectories as well as for various static poses using a phantom...
June 23, 2017: Physics in Medicine and Biology
https://www.readbyqxmd.com/read/28644798/joint-alignment-of-multiple-point-sets-with-batch-and-incremental-expectation-maximization
#8
Dimitrios Georgios Evangelidis, Radu Horaud
This paper addresses the problem of registering multiple point sets. Solutions to this problem are often approximated by repeatedly solving for pairwise registration, which results in an uneven treatment of the sets forming a pair: a model set and a data set. The main drawback of this strategy is that the model set may contain noise and outliers, which negatively affects the estimation of the registration parameters. In contrast, the proposed formulation treats all the point sets on an equal footing. Indeed, all the points are drawn from a central Gaussian mixture, hence the registration is cast into a clustering problem...
June 21, 2017: IEEE Transactions on Pattern Analysis and Machine Intelligence
https://www.readbyqxmd.com/read/28644688/intraosseous-administration-of-antidotes-a-systematic-review
#9
Audrée Elliott, Pierre-André Dubé, Amélie Cossette-Côté, Laura Patakfalvi, Eric Villeneuve, Martin Morris, Sophie Gosselin
CONTEXT: Intraosseous (IO) access is an established route of administration in resuscitation situations. Patients with serious poisoning presenting to the emergency department may require urgent antidote therapy. However, intravenous (IV) access is not always readily available. OBJECTIVE: This study reviews the current evidence for IO administration of antidotes that could be used in poisoning. The primary outcome was mortality as a surrogate of efficacy. Secondary outcomes included hemodynamic variables, electrocardiographic variables, neurological status, pharmacokinetics outcomes, and adverse effects as defined by each article...
June 23, 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28644669/entanglement-and-nonlocality-in-infinite-1d-systems
#10
Zizhu Wang, Sukhwinder Singh, Miguel Navascués
We consider the problem of detecting entanglement and nonlocality in one-dimensional (1D) infinite, translation-invariant (TI) systems when just near-neighbor information is available. This issue is deeper than one might think a priori, since, as we show, there exist instances of local separable states (classical boxes) which admit only entangled (nonclassical) TI extensions. We provide a simple characterization of the set of local states of multiseparable TI spin chains and construct a family of linear witnesses which can detect entanglement in infinite TI states from the nearest-neighbor reduced density matrix...
June 9, 2017: Physical Review Letters
https://www.readbyqxmd.com/read/28644561/the-redox-sensitive-module-of-cyclophilin-20-3-2-cysteine-peroxiredoxin-and-cysteine-synthase-integrates-sulfur-metabolism-and-oxylipin-signaling-in-the-high-light-acclimation-response
#11
Sara M Müller, Shanshan Wang, Wilena Telman, Michael Liebthal, Helena Schnitzer, Andrea Viehhauser, Carsten Sticht, Carolina Delatorre, Markus Wirtz, Rüdiger Hell, Karl-Josef Dietz
The integration of redox- and reactive oxygen species-dependent signaling and metabolic activities are fundamental to plant acclimation to biotic and abiotic stresses. Previous data suggest the existence of a dynamically interacting module in the chloroplast stroma consisting of cyclophilin 20-3 (Cyp20-3), O-acetylserine(thiol)lyase B (OASTL-B), 2-cysteine peroxiredoxins A/B (2-CysPrx) and serine acetyltransferase 2;1 (SERAT2;1). The functionality of this COPS module is influenced by redox stimuli and oxophytodienoic acid (OPDA) which is the precursor for jasmonic acid...
June 23, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28644475/post-translational-modification-of-ribosomally-synthesized-peptides-by-a-radical-sam-epimerase-in-bacillus-subtilis
#12
Alhosna Benjdia, Alain Guillot, Pauline Ruffié, Jérôme Leprince, Olivier Berteau
Ribosomally synthesized peptides are built out of L-amino acids, whereas D-amino acids are generally the hallmark of non-ribosomal synthetic processes. Here we show that the model bacterium Bacillus subtilis is able to produce a novel type of ribosomally synthesized and post-translationally modified peptide that contains D-amino acids, and which we propose to call epipeptides. We demonstrate that a two [4Fe-4S]-cluster radical S-adenosyl-L-methionine (SAM) enzyme converts L-amino acids into their D-counterparts by catalysing Cα-hydrogen-atom abstraction and using a critical cysteine residue as the hydrogen-atom donor...
July 2017: Nature Chemistry
https://www.readbyqxmd.com/read/28644433/ctla-4-mediated-posttranslational-modifications-direct-cytotoxic-t-lymphocyte-differentiation
#13
Holger Lingel, Josef Wissing, Aditya Arra, Denny Schanze, Stefan Lienenklaus, Frank Klawonn, Mandy Pierau, Martin Zenker, Lothar Jänsch, Monika C Brunner-Weinzierl
The blockade of inhibitory receptors such as CTLA-4 (CD152) is being used as immune-checkpoint therapy, offering a powerful strategy to restore effective immune responses against tumors. To determine signal components that are induced under the control of CTLA-4 we analyzed activated murine CD8(+) T cells by quantitative proteomics. Accurate mass spectrometry revealed that CTLA-4 engagement led to central changes in the phosphorylation of proteins involved in T-cell differentiation. Beside other targets, we discovered a CTLA-4-mediated induction of the translational inhibitor programmed cell death-4 (PDCD4) as a result of FoxO1 nuclear re-localization...
June 23, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28644430/the-clinical-landscape-for-sma-in-a-new-therapeutic-era
#14
REVIEW
K Talbot, E F Tizzano
Despite significant advances in basic research, the treatment of degenerative diseases of the nervous system remains one of the greatest challenges for translational medicine. The childhood onset motor neuron disorder spinal muscular atrophy (SMA) has been viewed as one of the more tractable targets for molecular therapy, due to a detailed understanding of the molecular genetic basis of the disease. In SMA, inactivating mutations in the SMN1 gene can be partially compensated for by limited expression of SMN protein from a variable number of copies of the SMN2 gene, which provides both a molecular explanation for phenotypic severity and a target for therapy...
June 23, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28644395/optical-tracking-and-digital-quantification-of-beating-behavior-in-bioengineered-human-cardiac-organoids
#15
Mahesh Devarasetty, Steven Forsythe, Thomas D Shupe, Shay Soker, Colin E Bishop, Anthony Atala, Aleksander Skardal
Organoid and organ-on-a-chip technologies are rapidly advancing towards deployment for drug and toxicology screening applications. Liver and cardiac toxicities account for the majority of drug candidate failures in human trials. Liver toxicity generally produces liver cell death, while cardiac toxicity causes adverse changes in heart beat kinetics. In traditional 2D cultures, beating kinetics can be measured by electrode arrays, but in some 3D constructs, quantifying beating kinetics can be more challenging...
June 23, 2017: Biosensors
https://www.readbyqxmd.com/read/28644301/palliative-oxygen-for-chronic-breathlessness-what-new-evidence
#16
Zainab Ahmadi, David C Currow, Magnus Ekström
PURPOSE OF REVIEW: Supplemental oxygen improves survival in patients with chronic obstructive pulmonary disease (COPD) and severe hypoxaemia, but the effect of oxygen therapy in mild or moderate hypoxaemia to reduce symptomatic chronic breathlessness remains unclear. This review provides an overview of recent evidence about the role of oxygen therapy for the relief of chronic breathlessness in advanced illness. RECENT FINDINGS: In COPD, a recent Cochrane review strengthens earlier findings regarding the positive effect of supplemental oxygen compared with air during exercise test in the training setting...
July 20, 2017: Current Opinion in Supportive and Palliative Care
https://www.readbyqxmd.com/read/28644300/breathlessness-in-the-primary-care-setting
#17
Noel Baxter
PURPOSE OF REVIEW: Breathlessness is a high-volume problem with 10% of adults experiencing the symptom daily placing a heavy burden on the health and wider economy. As it worsens, they enter the specialist and hospital-based symptom services where costs quickly escalate and people may find themselves in a place not of their choosing. For many, their care will be delivered by a disease or organ specialist and can find themselves passing between physicians without coordination for symptom support...
July 20, 2017: Current Opinion in Supportive and Palliative Care
https://www.readbyqxmd.com/read/28644150/rapid-fluorescence-lifetime-estimation-with-modified-phasor-approach-and-laguerre-deconvolution-a-comparative-study
#18
Farzad Fereidouni, Dimitris Gorpas, Dinglong Ma, Hussain Fatakdawala, Laura Marcu
Fluorescence lifetime imaging has been shown to serve as a valuable tool for interrogating and diagnosis of biological tissue at mesoscopic level. The ability to analyze fluorescence decay curves to extract lifetime values in real-time is crucial for clinical translation and applications such as tumor margin delineation or intracoronary imaging of atherosclerotic plaques. In this work, we compare the performance of two popular non-parametric (fit-free) methods for determining lifetime values from fluorescence decays in real-time -Phasor approach and Laguerre deconvolution...
June 23, 2017: Methods and Applications in Fluorescence
https://www.readbyqxmd.com/read/28644096/comparisons-between-commercial-salivary-testosterone-enzyme-linked-immunosorbent-assay-kits
#19
Christoffer R Andersson, Jonas Bergquist, Elvar Theodorsson, Jakob O Ström
INTRODUCTION: Measuring testosterone concentrations is of interest both in clinical situations and for research, the latter expanding rapidly during recent years. An increased demand for convenient methods has prompted a number of companies to develop enzyme-linked immunosorbent assay (ELISA) kits to measure testosterone concentrations in saliva. However, the inter-comparability of kits from different manufacturers have yet to be determined. AIM OF STUDY: The aim of this study was to compare commercially available ELISA kits from four different manufacturers (Salimetrics, IBL, DRG and Demeditec)...
June 23, 2017: Scandinavian Journal of Clinical and Laboratory Investigation
https://www.readbyqxmd.com/read/28644070/particulate-matter-disrupts-human-lung-endothelial-cell-barrier-integrity-via-rho-dependent-pathways
#20
Ting Wang, Yuka Shimizu, Xiaomin Wu, Gabriel T Kelly, Xiaoyan Xu, Lichun Wang, Zhongqing Qian, Yin Chen, Joe G N Garcia
Increased exposure to ambient particulate matter (PM) is associated with elevated morbidity and mortality in patients with cardiopulmonary diseases and cancer. We and others have shown that PM induces lung microvascular barrier dysfunction which potentially enhances the systemic toxicity of PM. However, the mechanisms by which PM disrupts vascular endothelial integrity remain incompletely explored. We hypothesize that PM induces endothelial cell (EC) cytoskeleton rearrangement via Rho GTPase-dependent pathways to facilitate vascular hyperpermeability...
June 23, 2017: Pulmonary Circulation
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