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https://www.readbyqxmd.com/read/28439615/wip1-phosphatase-as-pharmacological-target-in-cancer-therapy
#1
REVIEW
Soňa Pecháčková, Kamila Burdová, Libor Macurek
DNA damage response (DDR) pathway protects cells from genome instability and prevents cancer development. Tumor suppressor p53 is a key molecule that interconnects DDR, cell cycle checkpoints, and cell fate decisions in the presence of genotoxic stress. Inactivating mutations in TP53 and other genes implicated in DDR potentiate cancer development and also influence the sensitivity of cancer cells to treatment. Protein phosphatase 2C delta (referred to as WIP1) is a negative regulator of DDR and has been proposed as potential pharmaceutical target...
April 24, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28438832/a-photoconversion-model-for-full-spectral-programming-and-multiplexing-of-optogenetic%C3%A2-systems
#2
Evan J Olson, Constantine N Tzouanas, Jeffrey J Tabor
Optogenetics combines externally applied light signals and genetically engineered photoreceptors to control cellular processes with unmatched precision. Here, we develop a mathematical model of wavelength- and intensity-dependent photoconversion, signaling, and output gene expression for our two previously engineered light-sensing Escherichia coli two-component systems. To parameterize the model, we develop a simple set of spectral and dynamical calibration experiments using our recent open-source "Light Plate Apparatus" device...
April 24, 2017: Molecular Systems Biology
https://www.readbyqxmd.com/read/28438806/emerging-affinity-based-proteomic-technologies-for-large-scale-plasma-profiling-in-cardiovascular-disease
#3
REVIEW
J Gustav Smith, Robert E Gerszten
Plasma biomarkers that reflect molecular states of the cardiovascular system are central for clinical decision making. Routinely used plasma biomarkers include troponins, natriuretic peptides, and lipoprotein particles, yet interrogate only a modest subset of pathways relevant to cardiovascular disease. Systematic profiling of a larger portion of circulating plasma proteins (the plasma proteome) will provide opportunities for unbiased discovery of novel markers to improve diagnostic or predictive accuracy. In addition, proteomic profiling may inform pathophysiological understanding and point to novel therapeutic targets...
April 25, 2017: Circulation
https://www.readbyqxmd.com/read/28436113/using-predictions-from-a-joint-model-for-longitudinal-and-survival-data-to-inform-the-optimal-time-of-intervention-in-an-abdominal-aortic-aneurysm-screening-programme
#4
Michael J Sweeting
Joint models of longitudinal and survival data can be used to predict the risk of a future event occurring based on the evolution of an endogenous biomarker measured repeatedly over time. This has led naturally to the use of dynamic predictions that update each time a new longitudinal measurement is provided. In this paper, we show how such predictions can be utilised within a fuller decision modelling framework, in particular to allow planning of future interventions for patients under a 'watchful waiting' care pathway...
April 24, 2017: Biometrical Journal. Biometrische Zeitschrift
https://www.readbyqxmd.com/read/28435841/evading-plant-immunity-feedback-control-of-the-t3ss-in-pseudomonas-syringae
#5
COMMENT
Christopher Waite, Jörg Schumacher, Milija Jovanovic, Mark Bennett, Martin Buck
Microbes are responsible for over 10% of the global yield losses in staple crops such as wheat, rice, and maize. Understanding the decision-making strategies that enable bacterial plant pathogens to evade the host immune system and cause disease is essential for managing their ever growing threat to food security. Many utilise the needle-like type III secretion system (T3SS) to suppress plant immunity, by injecting effector proteins that inhibit eukaryotic signalling pathways into the host cell cytoplasm. Plants can in turn evolve resistance to specific pathogens via recognition and blocking of the T3SS effectors, so leading to an ongoing co-evolutionary 'arms race' between pathogen and host pairs...
March 17, 2017: Microbial Cell
https://www.readbyqxmd.com/read/28435499/the-fast-and-the-furious-low-risk-chest-pain-and-the-rapid-rule-out-protocol
#6
REVIEW
Maite Anna Huis In 't Veld, Louise Cullen, Simon A Mahler, Barbra E Backus, Zachary D W Dezman, Amal Mattu
Accelerated diagnostic pathways (ADP) have been designed to identify low-risk chest pain patients in the emergency department. This review article discusses the Asia-Pacific Evaluation of Chest Pain Trial (ASPECT) score, the Accelerated Diagnostic Protocol for Chest Pain Trial (ADAPT) score, the Emergency Department Assessment of Chest Pain Score (EDACS), the HEARTScore and the HEART pathway. These ADPs have been validated in various studies and aid the emergency provider with identifying the low-risk chest pain patient who is appropriate for discharge home, while at the same time highlighting those patients who would benefit from further in-patient work up...
April 2017: Western Journal of Emergency Medicine
https://www.readbyqxmd.com/read/28435496/-choosing-wisely-imaging-recommendations-initial-implementation-in-new-england-emergency-departments
#7
Ali S Raja, Arjun Venkatesh, Nathan Mick, Cristopher P Zabbo, Kohei Hasegawa, Janice A Espinola, Jane C Bittner, Carlos A Camargo
INTRODUCTION: In June 2016, the American College of Emergency Physicians (ACEP) Emergency Quality Network began its Reduce Avoidable Imaging Initiative, designed to "reduce testing and imaging with low risk patients through the implementation of Choosing Wisely recommendations." However, it is unknown whether New England emergency departments (ED) have already implemented evidence-based interventions to improve adherence to ACEP Choosing Wisely recommendations related to imaging after their initial release in 2013...
April 2017: Western Journal of Emergency Medicine
https://www.readbyqxmd.com/read/28432006/stepwise-use-of-circulatory-support-devices-in-a-patient-refractory-to-cardiopulmonary-resuscitation
#8
Marco Spartera, Richard J Jabbour, Mauro Chiarito, Michele De Bonis, Federico Pappalardo
This case describes the management of a patient admitted to an emergency department with general malaise, who deteriorated into cardiac arrest and refractory to advanced life support measures. After extracorporeal cardiopulmonary resuscitation (eCPR) with veno-arterial extracorporeal membrane oxygenation in association with an Impella 2.5 device, the patient underwent cardiac surgery (tissue aortic valve replacement, coronary artery bypass grafting and implantation of short-term paracorporeal left ventricular assist device)...
April 8, 2017: Cardiovascular Revascularization Medicine: Including Molecular Interventions
https://www.readbyqxmd.com/read/28431443/-surgical-and-interventional-therapy-of-mitral-valve-regurgitation
#9
Wolfgang Schillinger, Miriam Puls, Bernhard C Danner
Depending from the etiology of mitral valve pathology and surgical risk, mitral valve surgery is the therapy of choice for most degenerative mitral valve diseases. In isolated secondary mitral valve regurgitation, the indication for interventional or conservative therapy becomes more important. In severe left ventricular dysfunction heart transplantation has to be taken into consideration. If relevant coronary artery disease is present and bypass surgery is indicated, mitral valve surgery is mandatory in severe regurgitation and is subject to a benefit-risk evaluation in moderate regurgitation...
April 2017: Deutsche Medizinische Wochenschrift
https://www.readbyqxmd.com/read/28431168/identifying-new-susceptibility-genes-on-dopaminergic-and-serotonergic-pathways-for-the-framing-effect-in-decision-making
#10
Xiaoxue Gao, Jinting Liu, Pingyuan Gong, Junhui Wang, Wan Fang, Hongming Yan, Lusha Zhu, Xiaolin Zhou
The framing effect refers the tendency to be risk-averse when options are presented positively but be risk-seeking when the same options are presented negatively during decision-making. This effect has been found to be modulated by the serotonin transporter gene (SLC6A4) and the catechol-o-methyltransferase gene (COMT) polymorphisms, which are on the dopaminergic and serotonergic pathways and which are associated with affective processing. The current study aimed to identify new genetic variations of genes on dopaminergic and serotonergic pathways that may contribute to individual differences in the susceptibility to framing...
April 19, 2017: Social Cognitive and Affective Neuroscience
https://www.readbyqxmd.com/read/28430808/quantification-of-hypoxia-related-gene-expression-as-a-potential-approach-for-clinical-outcome-prediction-in-breast-cancer
#11
Abderrahim El Guerrab, Anne Cayre, Fabrice Kwiatkowski, Maud Privat, Jean-Marc Rossignol, Fabrice Rossignol, Frédérique Penault-Llorca, Yves-Jean Bignon
Breast cancers are solid tumors frequently characterized by regions with low oxygen concentrations. Cellular adaptations to hypoxia are mainly determined by "hypoxia inducible factors" that mediate transcriptional modifications involved in drug resistance and tumor progression leading to metastasis and relapse occurrence. In this study, we investigated the prognostic value of hypoxia-related gene expression in breast cancer. A systematic review was conducted to select a set of 45 genes involved in hypoxia signaling pathways and breast tumor progression...
2017: PloS One
https://www.readbyqxmd.com/read/28428191/the-role-of-minimal-residual-disease-testing-in-myeloma-treatment-selection-and-drug-development-current-value-and-future-applications
#12
Kenneth C Anderson, Daniel Auclair, Gary J Kelloff, Caroline C Sigman, Herve Avet-Loiseau, Ann T Farrell, Nicole J Gormley, Shaji K Kumar, Ola Landgren, Nikhil C Munshi, Michele Cavo, Faith E Davies, Alessandra Di Bacco, Jennifer S Dickey, Steven I Gutman, Howard R Higley, Mohamad A Hussein, J Milburn Jessup, Ilan R Kirsch, Richard F Little, Robert D Loberg, Jens G Lohr, Lata Mukundan, James L Omel, Trevor J Pugh, Gregory H Reaman, Michael D Robbins, A Kate Sasser, Nancy Valente, Elena Zamagni
Treatment of myeloma has benefited from the introduction of more effective and better tolerated agents, improvements in supportive care, better understanding of disease biology, revision of diagnostic criteria, and new sensitive and specific tools for disease prognostication and management. Assessment of minimal residual disease (MRD) in response to therapy is one of these tools, as longer progression-free survival (PFS) is seen consistently among patients who have achieved MRD negativity. Current therapies lead to unprecedented frequency and depth of response, and next generation flow and sequencing methods to measure MRD in bone marrow are in use and being developed with sensitivities in the range of 10(-5)‒10(-6) cells...
April 20, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28425445/scenario-dependence-of-future-changes-in-climate-extremes-under-1-5%C3%A2-%C3%A2-c-and-2%C3%A2-%C3%A2-c-global-warming
#13
Zhili Wang, Lei Lin, Xiaoye Zhang, Hua Zhang, Liangke Liu, Yangyang Xu
The 2015 Paris Agreement aims to limit global warming below 2 °C and pursue efforts to even limit it to 1.5 °C relative to pre-industrial levels. Decision makers need reliable information on the impacts caused by these warming levels for climate mitigation and adaptation measures. We explore the changes in climate extremes, which are closely tied to economic losses and casualties, under 1.5 °C and 2 °C global warming and their scenario dependence using three sets of ensemble global climate model simulations...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28423913/application-of-iata-a-case-study-in-evaluating-the-global-and-local-performance-of-a-bayesian-network-model-for-skin-sensitization
#14
J M Fitzpatrick, G Patlewicz
The information characterizing key events in an Adverse Outcome Pathway (AOP) can be generated from in silico, in chemico, in vitro and in vivo approaches. Integration of this information and interpretation for decision making are known as integrated approaches to testing and assessment (IATA). One such IATA was published by Jaworska et al., which describes a Bayesian network model known as ITS-2. The current work evaluated the performance of ITS-2 using a stratified cross-validation approach. We also characterized the impact of replacing the most significant component of the network, output from the expert system TIMES-SS, with structural alert information from the OECD Toolbox and Toxtree...
April 20, 2017: SAR and QSAR in Environmental Research
https://www.readbyqxmd.com/read/28423796/personalized-guideline-based-treatment-recommendations-using-natural-language-processing-techniques
#15
Matthias Becker, Britta Böckmann
Clinical guidelines and clinical pathways are accepted and proven instruments for quality assurance and process optimization. Today, electronic representation of clinical guidelines exists as unstructured text, but is not well-integrated with patient-specific information from electronic health records. Consequently, generic content of the clinical guidelines is accessible, but it is not possible to visualize the position of the patient on the clinical pathway, decision support cannot be provided by personalized guidelines for the next treatment step...
2017: Studies in Health Technology and Informatics
https://www.readbyqxmd.com/read/28422568/cgas-sting-tbk1-irf3-7-induced-interferon-%C3%AE-contributes-to-the-clearing-of-non-tuberculous-mycobacterial-infection-in-mice
#16
Nanthapon Ruangkiattikul, Andreas Nerlich, Ketema Abdissa, Stefan Lienenklaus, Abdulhadi Suwandi, Nina Janze, Kristin Laarmann, Julia Spanier, Ulrich Kalinke, Siegfried Weiss, Ralph Goethe
Type I interferons (IFN-I), such as IFN-α and IFN-β are important messengers in the host response against bacterial infections. Knowledge about the role of IFN-I in infections by nontuberculous mycobacteria (NTM) is limited. Here we show that macrophages infected with pathogens of the Mycobacterium avium complex produced significantly lower amounts of IFN-β than macrophages infected with the opportunistic pathogen M. smegmatis. To dissect the molecular mechanisms of this phenomenon, we focussed on the obligate pathogen Mycobacterium avium ssp...
April 19, 2017: Virulence
https://www.readbyqxmd.com/read/28419336/ip3r-mediated-ca2-signals-govern-hematopoietic-and-cardiac-divergence-of-flk1-cells-via-the-calcineurin-nfatc3-etv2-pathway
#17
Yi-Jie Wang, Jijun Huang, Wenqiang Liu, Xiaochen Kou, Huayuan Tang, Hong Wang, Xiujian Yu, Shaorong Gao, Kunfu Ouyang, Huang-Tian Yang
Ca2+ signals participate in various cellular processes with spatial and temporal dynamics, among which, inositol 1,4,5-trisphosphate receptors (IP3Rs)-mediated Ca2+ signals are essential for early development. However, the underlying mechanisms of IP3R-regulated cell fate decision remain largely unknown. Here we report that IP3Rs are required for the hematopoietic and cardiac fate divergence of mouse embryonic stem cells (mESCs). Deletion of IP3Rs (IP3R-tKO) reduced Flk1+/PDGFRα- hematopoietic mesoderm, c-Kit+/CD41+ hematopoietic progenitor cell population, and the colony-forming unit activity, but increased cardiac progenitor markers as well as cardiomyocytes...
April 13, 2017: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/28418939/exploring-the-molecular-pathogenesis-and-biomarkers-of-high-risk-oral-premalignant-lesions-on-the-basis-of-long-noncoding-rna-expression-profiling-by-serial-analysis-of-gene-expression
#18
Hongcheng Jia, Xuan Wang, Zheng Sun
Oral premalignant lesions (OPLs) have malignant transformation potential, with no reliable markers available. This study aimed to assess molecular events to identify biomarkers that can reflect high-risk lesions as predictive factors to tailor clinical decision for patients on the basis of long noncoding RNAs (lncRNA) expression profiling by serial analysis of gene expression. The GSE31021 and GSE8127 datasets were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) and lncRNAs were identified using the LIMMA package in R language...
April 24, 2017: European Journal of Cancer Prevention
https://www.readbyqxmd.com/read/28418404/a-pathway-linking-reward-circuitry-impulsive-sensation-seeking-and-risky-decision-making-in-young-adults-identifying-neural-markers-for-new-interventions
#19
H W Chase, J C Fournier, M A Bertocci, T Greenberg, H Aslam, R Stiffler, J Lockovich, S Graur, G Bebko, E E Forbes, M L Phillips
High trait impulsive sensation seeking (ISS) is common in 18-25-year olds, and is associated with risky decision-making and deleterious outcomes. We examined relationships among: activity in reward regions previously associated with ISS during an ISS-relevant context, uncertain reward expectancy (RE), using fMRI; ISS impulsivity and sensation-seeking subcomponents; and risky decision-making in 100, transdiagnostically recruited 18-25-year olds. ISS, anhedonia, anxiety, depression and mania were measured using self-report scales; clinician-administered scales also assessed the latter four...
April 18, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28416606/tra2a-promoted-paclitaxel-resistance-and-tumor-progression-in-triple-negative-breast-cancers-via-regulating-alternative-splicing
#20
Tieju Liu, Huizhi Sun, Dongwang Zhu, Xueyi Dong, Fang Liu, Xiaohui Liang, Chen Chen, Bing Shao, Meili Wang, Yi Wang, Baocun Sun
Treatment of triple-negative breast cancer (TNBC) has been challenging and paclitaxel (PTX) resistance is one of the major obstacles to the better prognosis. Deregulation of alternative splicing (AS) may contribute to tumor progression and chemotherapy resistance. Human AS factor TRA2 has two separate gene paralogs encoding TRA2A and TRA2B proteins. TRA2B is associated with cancer cell survival and therapeutic sensitivity. However the individual role of TRA2A in cancer progression has not been reported. Here we report that TRA2A facilitates proliferation and survival, migration and invasion of TNBC cells...
April 17, 2017: Molecular Cancer Therapeutics
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