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https://www.readbyqxmd.com/read/28106876/inhibition-of-innate-immune-cytosolic-surveillance-by-an-m-tuberculosis-phosphodiesterase
#1
Ruchi Jain Dey, Bappaditya Dey, Yue Zheng, Laurene S Cheung, Jie Zhou, David Sayre, Pankaj Kumar, Haidan Guo, Gyanu Lamichhane, Herman O Sintim, William R Bishai
Mycobacterium tuberculosis infection leads to cytosolic release of the bacterial cyclic dinucleotide (CDN) c-di-AMP and a host-generated CDN, cGAMP, both of which trigger type I interferon (IFN) expression in a STING-dependent manner. Here we report that M. tuberculosis has developed a mechanism to inhibit STING activation and the type I IFN response via the bacterial phosphodiesterase (PDE) CdnP, which mediates hydrolysis of both bacterial-derived c-di-AMP and host-derived cGAMP. Mutation of cdnP attenuates M...
February 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28101622/-use-of-vasopressors-and-inotropics-in-cardiogenic-shock
#2
H Lemm, S Dietz, M Janusch, M Buerke
Vasoactive drugs and inotropic agents are important for the hemodynamic management of cardiogenic shock. In this article the use of different vasoactive and ionotropic drugs in cardiogenic shock is presented. Hemodynamic management during cardiogenic shock occurs after initial moderate volume delivery by dobutamine to increase inotropism. If adequate perfusion pressures are not achieved norepinephrine is administered. If a sufficient increase in cardiac performance can still not be achieved by the treatment, administration of levosimendan or phosphodiesterase (PDE) inhibitors may be necessary...
January 18, 2017: Herz
https://www.readbyqxmd.com/read/28097089/selective-inhibition-of-phosphodiesterases-4-5-and-9-induces-hsp20-phosphorylation-and-attenuates-amyloid-beta-1-42-mediated-cytotoxicity
#3
Ryan T Cameron, Ellanor Whiteley, Jon P Day, Anna I Parachikova, George S Baillie
Phosphodiesterase (PDE) inhibitors are currently under evaluation as agents that may facilitate the improvement of cognitive impairment associated with Alzheimer's disease. Our aim was to determine whether inhibitors of PDEs 4, 5 and 9 could alleviate the cytotoxic effects of amyloid beta 1-42 (Aβ1-42) via a mechanism involving the small heatshock protein HSP20. We show that inhibition of PDEs 4, 5 and 9 but not 3 induces the phosphorylation of HSP20 which, in turn, increases the colocalisation between the chaperone and Aβ1-42 to significantly decrease the toxic effect of the peptide...
January 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28093982/pde7-selective-and-dual-inhibitors-advances-in-chemical-and-biological-research
#4
Agnieszka Jankowska, Artur Świerczek, Grażyna Chłoń-Rzepa, Maciej Pawłowski, Elżbieta Wyska
Phosphodiesterase 7 (PDE7) is an intracellular enzyme that specifically hydrolyses the second messenger, cyclic-3',5'-adenosine monophosphate (cAMP), into inactive non-cyclic nucleotide, 5'-AMP. To date, many structurally diverse compounds with PDE7 inhibitory properties have been described, including selective PDE7 inhibitors, dual PDE4/PDE7, PDE7/PDE8, and PDE7/GSK-3 inhibitors, and non-selective PDE inhibitors with high affinity for PDE7. Inhibitors of PDE7 provided beneficial effects in animal models of inflammatory and neurological disorders, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, and many others...
16, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28092955/flow-optimization-in-vascular-networks
#5
Radu C Cascaval, Ciro D'Apice, Maria Pia D'Arienzo, Rosanna Manzo
The development of mathematical models for studying phenomena observed in vascular networks is very useful for its potential applications in medicine and physiology. Detailed 3D studies of flow in the arterial system based on the Navier-Stokes equations require high computational power, hence reduced models are often used, both for the constitutive laws and the spatial domain. In order to capture the major features of the phenomena under study, such as variations in arterial pressure and flow velocity, the resulting PDE models on networks require appropriate junction and boundary conditions...
June 1, 2017: Mathematical Biosciences and Engineering: MBE
https://www.readbyqxmd.com/read/28092946/carcinogenesis-of-the-oral-cavity-environmental-causes-and-potential-prevention-by-black-raspberry
#6
Karam El-Bayoumy, Kun-Ming Chen, Shang-Min Zhang, Yuan-Wan Sun, Shantu Amin, Gary Stoner, Joseph B Guttenplan
Worldwide, cancers of the oral cavity and pharynx comprise the sixth most common malignancies. Histologically, more than 90% of oral cancers are squamous cell carcinoma (SCC). Epidemiologic data strongly support the role of exogenous factors such as tobacco, alcohol, and human papilloma virus infection as major causative agents. Avoidance of risk factors has only been partially successful, and survival rates have not improved despite advances in therapeutic approaches. Therefore, new or improved approaches to prevention and/or early detection are critical...
January 17, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28092671/pde4d-promotes-fak-mediated-cell-invasion-in-braf-mutated-melanoma
#7
J Delyon, A Servy, F Laugier, J André, N Ortonne, M Battistella, S Mourah, A Bensussan, C Lebbé, N Dumaz
The cyclic AMP (cAMP) signaling pathway is critical in melanocyte biology for regulating differentiation. It is downregulated by phosphodiesterase (PDE) enzymes, which degrade cAMP itself. In melanoma evidence suggests that inhibition of the cAMP pathway by PDE type 4 (PDE4) favors tumor progression. For example, in melanomas harboring RAS mutations, the overexpression of PDE4 is crucial for MAPK pathway activation and proliferation induced by oncogenic RAS. Here we showed that PDE4D is overexpressed in BRAF-mutated melanoma cell lines, constitutively disrupting the cAMP pathway activation...
January 16, 2017: Oncogene
https://www.readbyqxmd.com/read/28087462/impact-of-disease-linked-mutations-targeting-the-oligomerization-interfaces-of-aldehyde-dehydrogenase-7a1
#8
David A Korasick, John J Tanner, Michael T Henzl
Aldehyde dehydrogenase 7A1 (ALDH7A1) is involved in lysine catabolism, catalyzing the oxidation of α-aminoadipate semialdehyde to α-aminoadipate. Certain mutations in the ALDH7A1 gene, which are presumed to reduce catalytic activity, cause an autosomal recessive seizure disorder known as pyridoxine-dependent epilepsy (PDE). Although the genetic association between ALDH7A1 and PDE is well established, little is known about the impact of PDE-mutations on the structure and catalytic function of the enzyme. Herein we report the first study of the molecular consequences of PDE mutations using purified ALDH7A1 variants...
January 10, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28076654/estimating-varying-coefficients-for-partial-differential-equation-models
#9
Xinyu Zhang, Jiguo Cao, Raymond J Carroll
Partial differential equations (PDEs) are used to model complex dynamical systems in multiple dimensions, and their parameters often have important scientific interpretations. In some applications, PDE parameters are not constant but can change depending on the values of covariates, a feature that we call varying coefficients. We propose a parameter cascading method to estimate varying coefficients in PDE models from noisy data. Our estimates of the varying coefficients are shown to be consistent and asymptotically normally distributed...
January 11, 2017: Biometrics
https://www.readbyqxmd.com/read/28066993/developing-a-biomimetic-tooth-bud-model
#10
Elizabeth E Smith, Weibo Zhang, Nathan R Schiele, Ali Khademhosseini, Catherine K Kuo, Pamela C Yelick
A long-term goal is to bioengineer, fully functional, living teeth for regenerative medicine and dentistry applications. Biologically based replacement teeth would avoid insufficiencies of the currently used dental implants. Using natural tooth development as a guide, a model was fabricated using post-natal porcine dental epithelial (pDE), porcine dental mesenchymal (pDM) progenitor cells, and human umbilical vein endothelial cells (HUVEC) encapsulated within gelatin methacrylate (GelMA) hydrogels. Previous publications have shown that post-natal DE and DM cells seeded onto synthetic scaffolds exhibited mineralized tooth crowns composed of dentin and enamel...
January 8, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28063843/partial-differential-equation-techniques-for-analysing-animal-movement-a-comparison-of-different-methods
#11
Yi-Shan Wang, Jonathan R Potts
Recent advances in animal tracking have allowed us to uncover the drivers of movement in unprecedented detail. This has enabled modellers to construct ever more realistic models of animal movement, which aid in uncovering detailed patterns of space use in animal populations. Partial differential equations (PDEs) provide a popular tool for mathematically analysing such models. However, their construction often relies on simplifying assumptions which may greatly affect the model outcomes. Here, we analyse the effect of various PDE approximations on the analysis of some simple movement models, including a biased random walk, central-place foraging processes and movement in heterogeneous landscapes...
January 5, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28062949/can-cyclic-nucleotide-phosphodiesterase-inhibitors-be-drugs-for-parkinson-s-disease
#12
REVIEW
Dominic Ngima Nthenge-Ngumbau, Kochupurackal P Mohanakumar
Parkinson's disease (PD) has no known cure; available therapies are only capable of offering temporary, symptomatic relief to the patients. Varied therapeutic strategies that are clinically used for PD are pharmacological therapies including dopamine replacement therapies (with or without adjuvant), postsynaptic dopamine receptor stimulation, dopamine catabolism inhibitors and also anticholinergics. Surgical therapies like deep brain stimulation and ablative surgical techniques are also employed. Phosphodiesterases (PDEs) are enzymes that degrade the phosphodiester bond in the second messenger molecules, cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP)...
January 6, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28060942/white-cgmp-interaction-promotes-fast-locomotor-recovery-from-anoxia-in-adult-drosophila
#13
Chengfeng Xiao, R Meldrum Robertson
Increasing evidence indicates that the white (w) gene in Drosophila possesses extra-retinal functions in addition to its classical role in eye pigmentation. We have previously shown that w+ promotes fast and consistent locomotor recovery from anoxia, but how w+ modulates locomotor recovery is largely unknown. Here we show that in the absence of w+, several PDE mutants, especially cyclic guanosine monophosphate (cGMP)-specific PDE mutants, display wildtype-like fast locomotor recovery from anoxia, and that during the night time, locomotor recovery was light-sensitive in white-eyed mutant w1118, and light-insensitive in PDE mutants under w1118 background...
2017: PloS One
https://www.readbyqxmd.com/read/28055196/discovery-of-novel-phosphodiesterase-2a-inhibitors-by-structure-based-virtual-screening-structural-optimization-and-bioassay
#14
Chen Zhang, Ling-Jun Feng, Yiyou Huang, Deyan Wu, Zhe Li, Qian Zhou, Yinuo Wu, Hai-Bin Luo
Phosphodiesterase-2A (PDE2A) is a potential therapeutic target for treatment of Alzheimer's disease and pulmonary hypertension. However, most of the current PDE2A inhibitors have moderate selectivity over other PDEs. In the present study, we described the discovery of novel PDE2A inhibitors by structure-based virtual screening combining pharmacophore model screening, molecular docking, molecular dynamics simulations, and bioassay validation. Nine hits out of 30 molecules from the SPECS database (a hit rate of 30%) inhibited PDE2A with affinity less than 50 μM...
January 18, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28052870/phosphodiesterase-5-inhibition-ameliorates-angiotensin-ii-dependent-hypertension-and-renal-vascular-dysfunction
#15
Manuel Thieme, Sema Hayriye Sivritas, Evanthia Mergia, Sebastian Alexander Potthoff, Guang Yang, Lydia Hering, Katharina Grave, Henning Hoch, Lars Christian Rump, Johannes Stegbauer
Changes in renal hemodynamics have a major impact on blood pressure (BP). Angiotensin (Ang) II has been shown to induce vascular dysfunction by interacting with phosphodiesterases (PDE)1 and PDE5. The predominant PDE isoform responsible for renal vascular dysfunction in hypertension is unknown. Here, we measured effects of PDE5-(sildenafil) or PDE1-(vinpocetine) inhibition on renal blood flow (RBF), BP and renal vascular function in normotensive and hypertensive mice. During acute short-term Ang II infusion, sildenafil decreased BP and increased RBF in C57BL/6 (WT) mice...
January 4, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28050972/registration-of-mri-to-intraoperative-radiographs-for-target-localization-in-spinal-interventions
#16
T De Silva, A Uneri, M D Ketcha, S Reaungamornrat, J Goerres, M W Jacobson, S Vogt, G Kleinszig, A J Khanna, J-P Wolinsky, J H Siewerdsen
Decision support to assist in target vertebra localization could provide a useful aid to safe and effective spine surgery. Previous solutions have shown 3D-2D registration of preoperative CT to intraoperative radiographs to reliably annotate vertebral labels for assistance during level localization. We present an algorithm (referred to as MR-LevelCheck) to perform 3D-2D registration based on a preoperative MRI to accommodate the increasingly common clinical scenario in which MRI is used instead of CT for preoperative planning...
January 4, 2017: Physics in Medicine and Biology
https://www.readbyqxmd.com/read/28047667/th-cd-201-01-best-in-physics-therapy-assessment-of-thin-film-cdte-as-an-effective-detector-for-microdosimety-at-gold-tissue-interface
#17
N Paudel, D Shvydka, E Parsai
PURPOSE: Presence of interfaces between high and low atomic number materials, often encountered in diagnostic imaging and radiation therapy, leads to radiation dose perturbation. This phenomenon is characterized by a very narrow region of sharp dose enhancement at the interface. The rapid fall-off of the dose enhancement over a very short distance from the interface makes the experimental dosimetry nontrivial. We use an in-house-built inexpensive thin-film Cadmium Telluride (CdTe) photodetector to study this effect at the gold-tissue interface and verify our experimental results with Monte Carlo (MC) modeling...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28046551/we-ab-bra-09-registration-of-preoperative-mri-to-intraoperative-radiographs-for-automatic-vertebral-target-localization
#18
T De Silva, A Uneri, M Ketcha, S Reaungamornrat, J Goerres, S Vogt, G Kleinszig, J Wolinsky, J H Siewerdsen
PURPOSE: Accurate localization of target vertebrae is essential to safe, effective spine surgery, but wrong-level surgery occurs with surprisingly high frequency. Recent research yielded the "LevelCheck" method for 3D-2D registration of preoperative CT to intraoperative radiographs, providing decision support for level localization. We report a new method (MR-LevelCheck) to perform 3D-2D registration based on preoperative MRI, presenting a solution for the increasingly common scenario in which MRI (not CT) is used for preoperative planning...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28043897/natural-products-against-alzheimer-s-disease-pharmaco-therapeutics-and-biotechnological-interventions
#19
REVIEW
Abhijit Dey, Raktim Bhattacharya, Anuradha Mukherjee, Devendra Kumar Pandey
Alzheimer's disease (AD) is a severe, chronic and progressive neurodegenerative disease associated with memory and cognition impairment ultimately leading to death. It is the commonest reason of dementia in elderly populations mostly affecting beyond the age of 65. The pathogenesis is indicated by accumulation of the amyloid-beta (Aβ) plaques and neurofibrillary tangles (NFT) in brain tissues and hyperphosphorylation of tau protein in neurons. The main cause is considered to be the formation of reactive oxygen species (ROS) due to oxidative stress...
December 30, 2016: Biotechnology Advances
https://www.readbyqxmd.com/read/28039524/effects-of-cyclic-nucleotide-phosphodiesterases-pdes-on-mitochondrial-skeletal-muscle-functions
#20
REVIEW
Liliane Tetsi, Anne-Laure Charles, Stéphanie Paradis, Anne Lejay, Samy Talha, Bernard Geny, Claire Lugnier
Mitochondria play a critical role in skeletal muscle metabolism and function, notably at the level of tissue respiration, which conduct muscle strength as well as muscle survival. Pathological conditions induce mitochondria dysfunctions notably characterized by free oxygen radical production disturbing intracellular signaling. In that way, the second messengers, cyclic AMP and cyclic GMP, control intracellular signaling at the physiological and transcription levels by governing phosphorylation cascades. Both nucleotides are specifically and selectively hydrolyzed in their respective 5'-nucleotide by cyclic nucleotide phosphodiesterases (PDEs), which constitute a multi-genic family differently tissue distributed and subcellularly compartmentalized...
December 30, 2016: Cellular and Molecular Life Sciences: CMLS
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