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https://www.readbyqxmd.com/read/29471565/fibrolamellar-carcinoma-recent-advances-and-unresolved-questions-on-the-molecular-mechanisms
#1
Gadi Lalazar, Sanford M Simon
Fibrolamellar hepatocellular carcinoma (FLC) is a rare form of primary liver cancer that affects adolescents and young adults without underlying liver disease. Surgery remains the mainstay of therapy; however, most patients are either not surgical candidates or suffer from recurrence. There is no approved systemic therapy and the overall survival remains poor. Historically classified as a subtype of hepatocellular carcinoma (HCC), FLC has a unique clinical, histological, and molecular presentation. At the genomic level, FLC contains a single 400kB deletion in chromosome 19, leading to a functional DNAJB1-PRKACA fusion protein...
February 2018: Seminars in Liver Disease
https://www.readbyqxmd.com/read/29471495/arginine-methylation-of-the-c-terminus-rgg-motif-promotes-top3b-topoisomerase-activity-and-stress-granule-localization
#2
Lifeng Huang, Zhihao Wang, Nithya Narayanan, Yanzhong Yang
DNA topoisomerase 3B (TOP3B) is unique among all mammalian topoisomerases for its dual activities that resolve both DNA and RNA topological entanglements to facilitate transcription and translation. However, the mechanism by which TOP3B activity is regulated is still elusive. Here, we have identified arginine methylation as an important post-translational modification (PTM) for TOP3B activity. Protein arginine methyltransferase (PRMT) 1, PRMT3 and PRMT6 all methylate TOP3B in vitro at its C-terminal arginine (R) and glycine (G)-rich motif...
February 19, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29471489/the-h-subunit-of-the-restriction-endonuclease-cgli-contains-a-prototype-dead-z1-helicase-like-motor
#3
Paulius Toliusis, Giedre Tamulaitiene, Rokas Grigaitis, Donata Tuminauskaite, Arunas Silanskas, Elena Manakova, Ceslovas Venclovas, Mark D Szczelkun, Virginijus Siksnys, Mindaugas Zaremba
CglI is a restriction endonuclease from Corynebacterium glutamicum that forms a complex between: two R-subunits that have site specific-recognition and nuclease domains; and two H-subunits, with Superfamily 2 helicase-like DEAD domains, and uncharacterized Z1 and C-terminal domains. ATP hydrolysis by the H-subunits catalyses dsDNA translocation that is necessary for long-range movement along DNA that activates nuclease activity. Here, we provide biochemical and molecular modelling evidence that shows that Z1 has a fold distantly-related to RecA, and that the DEAD-Z1 domains together form an ATP binding interface and are the prototype of a previously undescribed monomeric helicase-like motor...
February 20, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29471464/poor-immunogenicity-not-vaccine-strain-egg-adaptation-may-explain-the-low-h3n2-influenza-vaccine-effectiveness-in-2012-13
#4
Sarah Cobey, Sigrid Gouma, Kaela Parkhouse, Benjamin S Chambers, Hildegund C Ertl, Kenneth E Schmader, Rebecca A Halpin, Xudong Lin, Timothy B Stockwell, Suman R Das, Emily Landon, Vera Tesic, Ilan Youngster, Benjamin A Pinsky, David E Wentworth, Scott E Hensley, Yonatan H Grad
Background: Influenza vaccination aims to prevent infection by influenza virus and reduce associated morbidity and mortality; however, vaccine effectiveness (VE) can be modest, especially for subtype A(H3N2). Low VE has been attributed to mismatches between the vaccine and circulating influenza strains and to the vaccine's elicitation of protective immunity in only a subset of the population. The low H3N2 VE in the 2012-2013 season was attributed to egg-adaptive mutations that created antigenic mismatch between the actual vaccine strain (IVR-165) and both the intended vaccine strain (A/Victoria/361/2011) and the predominant circulating strains (clades 3C...
February 20, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/29471432/effectiveness-of-seven-and-thirteen-valent-pneumococcal-conjugate-vaccines-in-a-schedule-without-a-booster-dose-a-ten-year-observational-study
#5
Sanjay Jayasinghe, Clayton Chiu, Helen Quinn, Rob Menzies, Robin Gilmour, Peter McIntyre
Background: Uniquely among high income countries, Australia uses a 3+0 schedule (3 primary doses; no booster) for infant pneumococcal conjugate vaccine since January 2005, initially 7-valent (PCV7) then 13-valent (PCV13) from July 2011. We measured vaccine effectiveness (VE) of both PCVs against invasive pneumococcal disease (IPD) by two methods. Method: Cases were IPD notifications to national surveillance system in children eligible for respective PCVs. For the case-control method, up to ten age-matched controls were derived from Australian Childhood Immunisation Register...
February 17, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/29471424/predicting-user-adherence-to-behavioral-ehealth-interventions-in-the-real-world-examining-which-aspects-of-intervention-design-matter-most
#6
Amit Baumel, Elad Yom-Tov
Existing frameworks have identified a range of intervention design features that may facilitate adherence to eHealth interventions; however, empirical data are lacking on whether intervention design features can predict user adherence in the real world-where the public access available tools-and whether some design aspects of behavioral eHealth interventions are more important than others in predicting adherence. This study examined whether intervention design qualities predict user adherence to behavioral eHealth interventions in real-world use and which qualities matter the most...
February 17, 2018: Translational Behavioral Medicine
https://www.readbyqxmd.com/read/29471397/a-conceptual-framework-the-musical-self-as-a-unique-pathway-to-outcomes-in-the-acute-pediatric-health-setting
#7
Helen Shoemark, Jo Rimmer, Janeen Bower, Belinda Tucquet, Lauren Miller, Michelle Fisher, Nicholas Ogburn, Beth Dun
This article reports on a project at the Royal Children's Hospital Melbourne in which the music therapy team synthesized their practice and related theories to propose a new conceptual framework for music therapy in their acute pediatric setting. The impetus for the project was the realization that in the process of producing key statements about the non-musical benefits of music therapy, the cost was often the suppression of information about the patient's unique musical potential as the major (mediating) pathway from referral reason, to music therapy, and to effective outcomes...
February 17, 2018: Journal of Music Therapy
https://www.readbyqxmd.com/read/29471350/structural-and-mechanistic-insights-into-uhrf1-mediated-dnmt1-activation-in-the-maintenance-dna-methylation
#8
Tao Li, Linsheng Wang, Yongming Du, Si Xie, Xi Yang, Fuming Lian, Zhongjun Zhou, Chengmin Qian
UHRF1 plays multiple roles in regulating DNMT1-mediated DNA methylation maintenance during DNA replication. The UHRF1 C-terminal RING finger functions as an ubiquitin E3 ligase to establish histone H3 ubiquitination at Lys18 and/or Lys23, which is subsequently recognized by DNMT1 to promote its localization onto replication foci. Here, we present the crystal structure of DNMT1 RFTS domain in complex with ubiquitin and highlight a unique ubiquitin binding mode for the RFTS domain. We provide evidence that UHRF1 N-terminal ubiquitin-like domain (UBL) also binds directly to DNMT1...
February 19, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29471343/onchocerciasis-in-yemen-moving-forward-towards-an-elimination-program
#9
Abdul-Samid Al-Kubati, Charles D Mackenzie, Daniel Boakye, Yasin Al-Qubati, Abdul-Rahim Al-Samie, Isam E Awad, Bjorn Thylefors, Adrian Hopkins
The onchocerciasis focus in Yemen has been known for many years as an endemic area with unique characteristics, notably the atypical and most severe form of onchodermatitis, known as sowda or reactive onchodermatitis (ROD). The national effort to control the disease began in 1992 as an individual case treatment program by administering ivermectin to those presenting with ROD. The challenging geography of the endemic area and the current political and military unrest both underscore a need for special approaches when attempting to eliminate onchocerciasis from this country...
March 1, 2018: International Health
https://www.readbyqxmd.com/read/29471338/transitioning-from-river-blindness-control-to-elimination-steps-toward-stopping-treatment
#10
Paul T Cantey, Sharon L Roy, Daniel Boakye, Upendo Mwingira, Eric A Ottesen, Adrian D Hopkins, Yao K Sodahlon
The transition from onchocerciasis control to elimination requires country programmes to rethink their approach to a variety of activities as they move from addressing morbidity to addressing transmission of the parasite. Although the 2016 WHO guidelines provide extensive recommendations, it was beyond the scope of the document to provide guidance on all aspects of the transition. This paper will discuss some of the important issues that programmes are grappling with as they transition to elimination and provide some potential approaches that programmes can use to address them...
March 1, 2018: International Health
https://www.readbyqxmd.com/read/29471256/consensus-research-priorities-for-paediatric-status-epilepticus-a-delphi-study-of-health-consumers-researchers-and-clinicians
#11
Jeremy Furyk, Robin Ray, Kerriane Watt, Stuart R Dalziel, Ed Oakely, Mark Mackay, Gabriel Dabscheck, Kate Riney, Franz E Babl
PURPOSE: Status epilepticus (SE) is a paediatric emergency with significant morbidity and mortality. Recommendations beyond first line care are not based on high quality evidence. Emergency physicians and neurologists are key stakeholders in managing this condition. A collaborative, widely consulted approach to identifying priorities can help direct limited research funds appropriately. The objectives of this study are to identify consensus research priorities in paediatric SE among experts and health consumers...
February 5, 2018: Seizure: the Journal of the British Epilepsy Association
https://www.readbyqxmd.com/read/29471209/genetic-engineering-of-host-organisms-for-pharmaceutical-synthesis
#12
REVIEW
Joseph H Collins, Eric M Young
Pharmaceutical production hosts may be derived from almost any organism, from Chinese Hamster Ovary (CHO) cell lines to isolated actinomycetes. Each host can be improved, historically only through adaptive evolution. Recently, the maturation of organism engineering has expanded the available models, methods, and tools for altering host phenotypes. New tools like CRISPR-associated endonucleases promise to enable precise cellular reprogramming and to access previously intractable hosts. In this review, we discuss the most recent advances in engineering several types of pharmaceutical production hosts...
February 19, 2018: Current Opinion in Biotechnology
https://www.readbyqxmd.com/read/29471133/neural-network-for-nonsmooth-pseudoconvex-optimization-with-general-convex-constraints
#13
Wei Bian, Litao Ma, Sitian Qin, Xiaoping Xue
In this paper, a one-layer recurrent neural network is proposed for solving a class of nonsmooth, pseudoconvex optimization problems with general convex constraints. Based on the smoothing method, we construct a new regularization function, which does not depend on any information of the feasible region. Thanks to the special structure of the regularization function, we prove the global existence, uniqueness and "slow solution" character of the state of the proposed neural network. Moreover, the state solution of the proposed network is proved to be convergent to the feasible region in finite time and to the optimal solution set of the related optimization problem subsequently...
February 5, 2018: Neural Networks: the Official Journal of the International Neural Network Society
https://www.readbyqxmd.com/read/29471102/high-fructose-diet-induced-metabolic-syndrome-pathophysiological-mechanism-and-treatment-by-traditional-chinese-medicine
#14
REVIEW
Ying Pan, Ling-Dong Kong
Fructose is a natural monosaccharide broadly used in modern society. Over the past few decades, epidemiological studies have demonstrated that high fructose intake is an etiological factor of metabolic syndrome (MetS). This review highlights research advances on fructose-induced MetS, especially the underlying pathophysiological mechanism as well as pharmacotherapy by traditional Chinese medicine (TCM), using the PubMed, Web of science, China National Knowledge Infrastructure, China Science and Technology Journal and Wanfang Data...
February 19, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29470999/mast-cells-regulate-cd4-t-cell-differentiation-in-absence-of-antigen-presentation
#15
Hector Rodriguez Cetina Biefer, Timm Heinbokel, Hirofumi Uehara, Virginia Camacho, Koichiro Minami, Yeqi Nian, Suresh Koduru, Rachid El Fatimy, Ionita Ghiran, Alexander J Trachtenberg, Miguel A de la Fuente, Haruhito Azuma, Omid Akbari, Stefan G Tullius, Anju Vasudevan, Abdallah Elkhal
BACKGROUND: Given their unique capacity for antigen uptake, processing, and presentation, antigen presenting cells (APCs) are critical for initiating and regulating innate and adaptive immune responses. We have previously shown the role of nicotinamide adenine dinucleotide (NAD+ ) in T cell differentiation independently of the cytokine milieu, while the precise mechanisms remained unknown. OBJECTIVE: The objective of this study is to further dissect the mechanism of actions of NAD+ , and to determine the impact of APCs on NAD+ -mediated T cell activation...
February 19, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29470992/control-of-cell-fraction-and-population-recovery-during-tissue-regeneration-in-stem-cell-lineages
#16
Marissa Renardy, Alexandra Jilkine, Leili Shahriyari, Ching-Shan Chou
Multicellular tissues are continually turning over, and homeostasis is maintained through regulated proliferation and differentiation of stem cells and progenitors. Following tissue injury, a dramatic increase in cell proliferation is commonly observed, resulting in rapid restoration of tissue size. This regulation is thought to occur via multiple feedback loops acting on cell self-renewal or differentiation. Models of ordinary differential equations have been widely used to study the cell lineage system. Prior modeling studies have suggested that loss of homeostasis and initiation of tumorigenesis can be contributed to the loss of control of these processes, and the rate of symmetric versus asymmetric division of the stem cells may also be altered...
February 19, 2018: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/29470975/high-throughput-screening-of-t7-phage-display-and-protein-microarrays-as-a-methodological-approach-for-the-identification-of-ige-reactive-components
#17
P San Segundo-Acosta, M Garranzo-Asensio, C Oeo-Santos, A Montero-Calle, J Quiralte, J Cuesta-Herranz, M Villalba, R Barderas
Olive pollen and yellow mustard seeds are major allergenic sources with high clinical relevance. To aid with the identification of IgE-reactive components, the development of sensitive methodological approaches is required. Here, we have combined T7 phage display and protein microarrays for the identification of allergenic peptides and mimotopes from olive pollen and mustard seeds. The identification of these allergenic sequences involved the construction and biopanning of T7 phage display libraries of mustard seeds and olive pollen using sera from allergic patients to both biological sources together with the construction of phage microarrays printed with 1536 monoclonal phages from the third/four rounds of biopanning...
February 19, 2018: Journal of Immunological Methods
https://www.readbyqxmd.com/read/29470956/metabolomic-insights-into-the-effects-of-thyroid-hormone-on-rana-lithobates-catesbeiana-metamorphosis-using-whole-body-matrix-assisted-laser-desorption-ionization-mass-spectrometry-imaging-maldi-msi
#18
Teesha C Luehr, Emily M Koide, Xiaodong Wang, Jun Han, Christoph H Borchers, Caren C Helbing
Anuran metamorphosis involves the transformation of an aquatic tadpole into a juvenile frog. This process is completely dependent upon thyroid hormones (THs). Although much research has been focused on changes in gene expression programs during this postembryonic developmental period, transitions in the metabolic profiles are relatively poorly understood. Matrix Assisted Laser Desorption/Ionization-Mass Spectrometry Imaging (MALDI-MSI) is a technique that generates highly multiplexed mass spectra while retaining spatial location information on a thin tissue section...
February 19, 2018: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/29470954/the-optical-properties-of-rat-porcine-and-human-lenses-in-organ-culture-treated-with-dexamethasone
#19
Mark Bree, Douglas Borchman
Organ culturing of lenses is useful for testing the direct effect of moieties such as cations, glucose, oxygen, antioxidants or drugs on the lens. Lens opacity changes in organ cultured lenses have never been measured quantitatively. Our aims were twofold: to establish the time course of lens opacity changes in organ cultured rat, porcine and human lenses and to test the utility of our system to measure opacity changes in lenses treated with dexamethasone. Human, porcine and rat lenses were incubated with or without 5 μM dexamethasone in minimum essential medium for 13 days...
February 19, 2018: Experimental Eye Research
https://www.readbyqxmd.com/read/29470910/fluctuation-in-interface-and-electronic-structure-of-single-molecule-junctions-investigated-by-current-versus-bias-voltage-characteristics
#20
Yuji Isshiki, Shintaro Fujii, Tomoaki Nishino, Manabu Kiguchi
Structural and electronic detail at the metal-molecule interface has a significant impact on the charge transport across the molecular junctions, but its precise understanding and control still remain elusive. On the single-molecule scale, the metal-molecule interface structures and relevant charge transport properties are subject to fluctuation, which contains fundamental science of the single-molecule transport and implication for manipulability of the transport properties in the electronic devices. Here, we present a comprehensive approach to investigate the fluctuation in the metal-molecule interface in single-molecule junctions, based on current-voltage (I-V) measurements in combination with first-principles simulation...
February 22, 2018: Journal of the American Chemical Society
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